Background
Methods
Search methodology
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Concerned with (specifically) ovarian cancer
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Patients were treated with chemotherapy
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Gene expression was measured for use in predictions
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Predictions are related to a measure of chemoresistance (e.g. response rates, progression-free survival)
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Measurements were taken on human tissue (not cell lines)
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The research aim is to develop a diagnostic tool or predict response
Filtering
Data extraction
Bias analysis
Gene set enrichment
Ethics statement
Results
Study | Journal | No. samples | No. genes in study | No. genes in signature |
---|---|---|---|---|
Jeong et al. [22] | Anticancer Res. | 487 | 612 | 388, 612 |
Lisowska et al. [23] | Front. Oncol. | 127 | >47000 | 0 |
Roque et al. [24] | Clin. Exp. Metastasis | 48 | 1 | 1 |
Li et al. [3] | Oncol. Rep. | 44 | 1 | 1 |
Schwede et al. [25] | PLoS ONE | 663 | 2632 | 51 |
Verhaak et al. [26] | J. Clin. Invest. | 1368 | 11861 | 100 |
Obermayr et al. [27] | Gynecol. Oncol. | 255 | 29098 | 12 |
Han et al. [28] | PLoS ONE | 322 | 12042 | 349, 18 |
Hsu et al. [29] | BMC Genomics | 168 | 12042 | 134 |
Lui et al. [30] | PLoS ONE | 737 | NS | 227 |
Kang et al. [31] | J. Nat. Cancer Inst. | 558 | 151 | 23 |
Gillet et al. [32] | Clin. Cancer Res. | 80 | 356 | 11 |
Ferriss et al. [33] | PLos ONE | 341 | NS | 251, 125 |
Brun et al. [34] | Oncol. Rep. | 69 | 6 | 0 |
Skirnisdottir and Seidal [35] | Oncol. Rep. | 105 | 3 | 2 |
Brenne et al. [36] | Hum. Pathol. | 140 | 1 | 1 |
Sabatier et al. [37] | Br. J. Cancer | 401 | NS | 7 |
Gillet et al. [38] | Mol. Pharmeceutics | 32 | 350 | 18, 10, 6 |
Chao et al. [39] | BMC Med. Genomics | 6 | 8173 | NS |
Schlumbrecht et al. [40] | Mod. Pathol. | 83 | 7 | 2 |
Glaysher et al. [41] | Br. J. Cancer | 31 | 91 | 10, 4, 3, 5, 5, 11, 6, 6 |
Yan et al. [42] | Cancer Res. | 42 | 2 | 1 |
Yoshihara et al. [43] | PLoS ONE | 197 | 18176 | 88 |
Williams et al. [44] | Cancer Res. | 242 | NS | 15 to 95 |
Denkert et al. [45] | J. Pathol | 198 | NS | 300 |
Matsumura et al. [46] | Mol. Cancer Res. | 157 | 22215 | 250 |
Crijns et al. [47] | PLoS Medicine | 275 | 15909 | 86 |
Mendiola et al. [48] | PLoS ONE | 61 | 82 | 34 |
Gevaert et al. [49] | BMC Cancer | 69 | ∼24000 | ∼3000 |
Bachvarov et al. [50] | Int. J. Oncol. | 42 | 20174 | 155, 43 |
Netinatsunthorn et al. [51] | BMC Cancer | 99 | 1 | 1 |
De Smet et al. [52] | Int. J. Gynecol. Cancer | 20 | 21372 | 3000 |
Helleman et al. [53] | Int. J. Cancer | 96 | NS | 9 |
Spentzos et al. [54] | J. Clin. Oncol. | 60 | NS | 93 |
Jazaeri et al. [55] | Clin. Cancer Res. | 40 | 40033, 7585 | 85, 178 |
Raspollini et al. [56] | Int. J. Gynecol. Cancer | 52 | 2 | 2 |
Hartmann et al. [57] | Clin. Cancer Res. | 79 | 30721 | 14 |
Spentzos et al. [58] | J. Clin. Oncol. | 68 | 12625 | 115 |
Selvanayagam et al. [59] | Cancer Genet. Cytogenet. | 8 | 10692 | NS |
Iba et al. [60] | Cancer Sci. | 118 | 4 | 1 |
Kamazawa et al. [61] | Gynecol. Oncol. | 27 | 3 | 1 |
Vogt et al. [62] | Acta Biochim. Pol. | 17 | 3 | 0 |
Study | Tissue source | % Cancerous tissue |
---|---|---|
Jeong et al. [22] | ||
Lisowska et al. [23] | Fresh-frozen | NS |
Roque et al. [24] | FFPE, Fresh-frozen | min. 70% |
Li et al. [3] | FFPE | NS |
Schwede et al. [25] | ||
Verhaak et al. [26] | ||
Obermayr et al. [27] | Fresh-frozen, Blood | NS |
Han et al. [28] | ||
Hsu et al. [29] | ||
Lui et al. [30] | ||
Kang et al. [31] | ||
Gillet et al. [32] | Fresh-frozen | min. 75% |
Ferriss et al. [33] | FFPE | min. 70% |
Brun et al. [34] | FFPE | NS |
Skirnisdottir and Seidal [35] | FFPE | NS |
Brenne et al. [36] | Fresh-frozen effusion, Fresh-frozen | min. 50% |
Sabatier et al. [37] | Fresh-frozen | min. 60% |
Gillet et al. [38] | Fresh-frozen effusion | NS |
Chao et al. [39] | ||
Schlumbrecht et al. [40] | Fresh-frozen | min. 70% |
Glaysher et al. [41] | FFPE, Fresh | min. 80% |
Yan et al. [42] | Fresh-frozen | NS |
Yoshihara et al. [43] | Fresh-frozen | min. 80% |
Williams et al. [44] | ||
Denkert et al. [45] | Fresh-frozen | NS |
Matsumura et al. [46] | Fresh-frozen | NS |
Crijns et al. [47] | Fresh-frozen | median = 70% |
Mendiola et al. [48] | FFPE | min. 80% |
Gevaert et al. [49] | Fresh-frozen | NS |
Bachvarov et al. [50] | Fresh-frozen | min. 70% |
Netinatsunthorn et al. [51] | FFPE | NS |
De Smet et al. [52] | Not specified | NS |
Helleman et al. [53] | Fresh-frozen | median = 64% |
Spentzos et al. [54] | Fresh-frozen | NS |
Jazaeri et al. [55] | FFPE, Fresh-frozen | NS |
Raspollini et al. [56] | FFPE | NS |
Hartmann et al. [57] | Fresh-frozen | min. 70% |
Spentzos et al. [58] | Fresh-frozen | NS |
Selvanayagam et al. [59] | Fresh-frozen | min. 70% |
Iba et al. [60] | FFPE, Fresh-frozen | NS |
Kamazawa et al. [61] | FFPE, Fresh-frozen | NS |
Vogt et al. [62] | None specified | NS |
Study | Immunohistochemistry | TaqMan array | q-RT-PCR | Commercial microarray | Custom microarray | RT-PCR |
---|---|---|---|---|---|---|
Jeong et al. [22] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Lisowska et al. [23] | ✗ | ✗ | ✓ | ✓ | ✗ | ✗ |
Roque et al. [24] | ✓ | ✗ | ✓ | ✗ | ✗ | ✗ |
Li et al. [3] | ✓ | ✗ | ✗ | ✗ | ✗ | ✗ |
Schwede et al. [25] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Verhaak et al. [26] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Obermayr et al. [27] | ✗ | ✗ | ✓ | ✓ | ✗ | ✗ |
Han et al. [28] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Hsu et al. [29] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Lui et al. [30] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Kang et al. [31] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Gillet et al. [32] | ✗ | ✓ | ✗ | ✗ | ✗ | ✗ |
Ferriss et al. [33] | ✗ | ✗ | ✗ | ✗ | ✓ | ✗ |
Brun et al. [34] | ✓ | ✗ | ✗ | ✗ | ✗ | ✗ |
Skirnisdottir and Seidal [35] | ✓ | ✗ | ✗ | ✗ | ✗ | ✗ |
Brenne et al. [36] | ✗ | ✗ | ✓ | ✗ | ✗ | ✗ |
Sabatier et al. [37] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Gillet et al. [38] | ✗ | ✓ | ✗ | ✗ | ✗ | ✗ |
Chao et al. [39] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Schlumbrecht et al. [40] | ✓ | ✗ | ✓ | ✗ | ✗ | ✗ |
Glaysher et al. [41] | ✗ | ✓ | ✗ | ✗ | ✗ | ✗ |
Yan et al. [42] | ✓ | ✗ | ✗ | ✗ | ✗ | ✗ |
Yoshihara et al. [43] | ✗ | ✗ | ✓ | ✓ | ✗ | ✗ |
Williams et al. [44] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Denkert et al. [45] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Matsumura et al. [46] | ✓ | ✗ | ✓ | ✓ | ✗ | ✗ |
Crijns et al. [47] | ✗ | ✗ | ✓ | ✗ | ✓ | ✗ |
Mendiola et al. [48] | ✗ | ✓ | ✗ | ✗ | ✗ | ✗ |
Gevaert et al. [49] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Bachvarov et al. [50] | ✗ | ✗ | ✓ | ✓ | ✗ | ✗ |
Netinatsunthorn et al. [51] | ✓ | ✗ | ✗ | ✗ | ✗ | ✗ |
De Smet et al. [52] | ✗ | ✗ | ✗ | ✗ | ✓ | ✗ |
Helleman et al. [53] | ✗ | ✗ | ✓ | ✗ | ✓ | ✗ |
Spentzos et al. [54] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Jazaeri et al. [55] | ✓ | ✗ | ✗ | ✗ | ✓ | ✗ |
Raspollini et al. [56] | ✓ | ✗ | ✗ | ✗ | ✗ | ✗ |
Hartmann et al. [57] | ✗ | ✗ | ✗ | ✗ | ✓ | ✗ |
Spentzos et al. [58] | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ |
Selvanayagam et al. [59] | ✗ | ✗ | ✗ | ✗ | ✓ | ✗ |
Iba et al. [60] | ✓ | ✗ | ✓ | ✗ | ✗ | ✗ |
Kamazawa et al. [61] | ✗ | ✗ | ✓ | ✗ | ✗ | ✗ |
Vogt et al. [62] | ✗ | ✗ | ✗ | ✗ | ✗ | ✓ |
Study | Sub-type | Stage |
---|---|---|
Jeong et al. [22] | Serous, Endometrioid, Adenocarcinoma | I, II, III, IV |
Lisowska et al. [23] | Serous, Endometrioid, Clear cell, Undifferentiated | II, III, IV |
Roque et al. [24] | Serous, Endometrioid, Clear cell, Undifferentiated, Mixed | IIIC, IV |
Li et al. [3] | Serous, Endometrioid, Clear cell, Mucinous, Transitional | II, III, IV |
Schwede et al. [25] | Serous, Endometrioid, Clear cell, Mucinous, Adenocarcinoma, OSE | I, II, III, IV |
Verhaak et al. [26] | NS | II, III, IV |
Obermayr et al. [27] | Serous, Non-serous | II, III, IV |
Han et al. [28] | Serous, Endometrioid, Clear cell, Mucinous, Mixed, Poorly differentiated | II, III, IV |
Hsu et al. [29] | NS | III, IV |
Lui et al. [30] |
Serous
| II, III, IV |
Kang et al. [31] |
Serous
| I, II, III, IV |
Gillet et al. [32] |
Serous
| III, IV |
Ferriss et al. [33] | Serous, Clear cell, Other | III, IV |
Brun et al. [34] | Serous, Endometrioid, Clear cell, Mucinous, Other | III, IV |
Skirnisdottir and Seidal [35] | Serous, Endometrioid, Clear cell, Mucinous, Anaplastic | I, II |
Brenne et al. [36] | Serous, Endometrioid, Clear cell, Undifferentiated, Mixed | II, III, IV |
Sabatier et al. [37] | Serous, Endometrioid, Clear cell, Mucinous, Undifferentiated, Mixed | I, II, III, IV |
Gillet et al. [38] |
Serous
| III, IV, NS |
Chao et al. [39] | NS | NS |
Schlumbrecht et al. [40] |
Serous
| III, IV |
Glaysher et al. [41] | Serous, Endometrioid, Clear cell, Mucinous, Mixed, Poorly differentiated | IIIC, IV |
Yan et al. [42] | Serous, Endometrioid, Clear cell, Mucinous, Transitional | II, III, IV |
Yoshihara et al. [43] |
Serous
| III, IV |
Williams et al. [44] | Serous, Endometrioid, Undifferentiated | III, IV |
Denkert et al. [45] | Serous, Non-serous, Undifferentiated | I, II, III, IV |
Matsumura et al. [46] |
Serous
| I, II, III, IV |
Crijns et al. [47] |
Serous
| III, IV |
Mendiola et al. [48] | Serous, Non-serous | III, IV |
Gevaert et al. [49] | Serous, Endometrioid, Mucinous, Mixed | I, III, IV |
Bachvarov et al. [50] | Serous, Endometrioid, Clear cell | II, III, IV |
Netinatsunthorn et al. [51] |
Serous
| III, IV |
De Smet et al. [52] | Serous, Endometrioid, Mucinous, Mixed | I, III, IV |
Helleman et al. [53] | Serous, Endometrioid, Clear cell, Mucinous, Mixed, Poorly differentiated | I/II, III/IV |
Spentzos et al. [54] | Serous, Endometrioid, Clear cell, Mixed | I, II, III, IV |
Jazaeri et al. [55] | Serous, Endometrioid, Clear cell, Mixed, Undifferentiated, Carcinoma | II, III, IV |
Raspollini et al. [56] |
Serous
|
IIIC
|
Hartmann et al. [57] | Serous, Endometrioid, Mixed | II, III, IV |
Spentzos et al. [58] | Serous, Endometrioid, Clear cell, Mixed | I, II, III, IV |
Selvanayagam et al. [59] | Serous, Endometrioid, Clear cell, Undifferentiated | III, IV |
Iba et al. [60] | Serous, Endometrioid, Clear cell, Mixed | I, II, III, IV |
Kamazawa et al. [61] | Serous, Endometrioid, Clear cell | III, IV |
Vogt et al. [62] | NS | NS |
Study | Patient prior chemotherapy treatment | Model accounts for the different chemotherapies? | Prognostic or predictive? | Model validated? |
---|---|---|---|---|
Jeong et al. [22] | Platinum-based | ✓ | Predictive | ✓ |
Lisowska et al. [23] | Platinum/Cyclophosphamide, Platinum/Taxane | ✗ | Prognostic | ✓ |
Roque et al. [24] | NS | ✗ | Prognostic | ✗ |
Li et al. [3] | Platinum/Cyclophosphamide, Platinum/Taxane | ✗ | Prognostic | ✗ |
Schwede et al. [25] | NS | ✗ | Prognostic | ✓ |
Verhaak et al. [26] | NS | ✗ | Prognostic | ✓ |
Obermayr et al. [27] | Platinum-based | ✗ | Prognostic | ✗ |
Han et al. [28] | Platinum/Paclitaxel | Prognostic | ✓ | |
Hsu et al. [29] | Platinum/Paclitaxel | |||
+ additional treatments | ✓ | Prognostic | ✓ | |
Lui et al. [30] | NS | ✗ | Prognostic | ✓ |
Kang et al. [31] | Platinum/Taxane | Prognostic | ✓ | |
Gillet et al. [32] | Carboplatin/Paclitaxel | Prognostic | ✓ | |
Ferriss et al. [33] | Platinum-based | ✓ | Predictive | ✓ |
Brun et al. [34] | NS | ✗ | Prognostic | ✗ |
Skirnisdottir and Seidal [35] | Carboplatin/Paclitaxel | Prognostic | ✗ | |
Brenne et al. [36] | NS | ✗ | Prognostic | ✗ |
Sabatier et al. [37] | Platinum-based | ✗ | Prognostic | ✓ |
Gillet et al. [38] | NS | ✗ | Prognostic | ✓ |
Chao et al. [39] | NS | ✗ | Prognostic | ✗ |
Schlumbrecht et al. [40] | Platinum/Taxane | Prognostic | ✗ | |
Glaysher et al. [41] | Platinum, Platinum/Paclitaxel | ✓ | Predictive | ✓ |
Yan et al. [42] | Platinum-based | ✗ | Prognostic | ✗ |
Yoshihara et al. [43] | Platinum/Taxane | Prognostic | ✓ | |
Williams et al. [44] | NS | ✓ | Predictive | ✓ |
Denkert et al. [45] | Carboplatin/Paclitaxel | Prognostic | ✓ | |
Matsumura et al. [46] | Platinum-based | ✓ | Predictive | ✓ |
Crijns et al. [47] | Platinum, Platinum/ | |||
Cyclophosphamide, Platinum/Paclitaxel | ✓ | Prognostic | ✓ | |
Mendiola et al. [48] | Platinum/Taxane | Prognostic | ✓ | |
Gevaert et al. [49] | NS | ✗ | Prognostic | ✓ |
Bachvarov et al. [50] | Carboplatin/Paclitaxel, | |||
Carboplatin/Cyclophosphamide, Cisplatin/Paclitaxel | ✗ | Prognostic | ✓ | |
Netinatsunthorn et al. [51] | Platinum/Cyclophosphamide | Prognostic | ✗ | |
De Smet et al. [52] | Platinum/Cyclophosphamide, Platinum/Paclitaxel | ✗ | Prognostic | ✓ |
Helleman et al. [53] | Platinum/Cyclophosphamide, Platinum-based | ✗ | Prognostic | ✓ |
Spentzos et al. [54] | Platinum/Taxane | Prognostic | ✓ | |
Jazaeri et al. [55] | Carboplatin/Paclitaxel, Cisplatin/Cyclophosphamide, Carboplatin/Docetaxel, Carboplatin | ✗ | Prognostic | ✓ |
Raspollini et al. [56] | Cisplatin/Cyclophosphamide, Carboplatin/Cyclophosphamide, Carboplatin/Paclitaxel | ✗ | Prognostic | ✗ |
Hartmann et al. [57] | Cisplatin/Paclitaxel, Carboplatin/Paclitaxel | ✗ | Prognostic | ✓ |
Spentzos et al. [58] | Platinum/Taxane | Prognostic | ✓ | |
Selvanayagam et al. [59] | Cisplatin/Cyclophosphamide, Carboplatin/Cyclophosphamide, Cisplatin/Paclitaxel | ✗ | Prognostic | ✓ |
Iba et al. [60] | Carboplatin/Paclitaxel | Prognostic | ✗ | |
Kamazawa et al. [61] | Carboplatin/Paclitaxel | Prognostic | ✗ | |
Vogt et al. [62] | Etoposide, Paclitaxel/Epirubicin, Carboplatin/Paclitaxel | ✓ | Predictive | ✗ |
Study | Prediction | Prediction method | Predictive ability |
---|---|---|---|
Jeong et al. [22] | Overall Survival | Student’s T test, Hierarchical clustering, Compound covariate predictor algorithm, Cox proportional hazards regression, Kaplan-Meier curves, Log-rank test, ROC analysis | ‘Taxane-based treatment significantly affected OS for patients in the YA subgroup (3 year rate: 74.4% with taxane vs. 37.9% without taxane, p=0.005 by log-rank test)’, ‘estimated hazard ratio for death after taxane-based treatment in the YA subgroup was 0.5 (95% CI=0.31−−0.82,p=0.005)’ |
Lisowska et al. [23] | Chemoresponse, Disease-Free Survival, Overall Survival | Support vector machines, Kaplan-Meier curves, Log-rank test | No genes found to be significant in the training set were significant in the test set, for chemoresponse, DFS or OS |
Roque et al. [24] | Overall Survival | Kaplan-Meier curves, Log-rank test, Student’s T test | ‘OS was predicted by increased class III β-tubulin staining by both tumor (HR3.66, 96%CI=1.11–12.1, p=0.03) and stroma (HR4.53, 95%CI=1.28–16.1, p=0.02)’ |
Li et al. [3] | Chemoresponse (chemoresistant vs. chemosensitive) | Correlation of p-CFL1 staining and chemoresponse | ‘immunostaining of p-CFL1 was positive in 77.3% of chemosensitive and in 95.9% of the chemoresistant’ (p=0.014, U=157.5) |
Schwede et al. [25] | Stem cell-like subtype, Disease-Free Survival, Overall Survival | ISIS unsupervised bipartitioning, Diagonal linear discriminant analysis, Gaussian mixture modelling, Kaplan-Meier curves, Log-rank test | OS (p values): Dressman =0.0354, Crijns =0.021, Tothill =4.4E−7 |
Verhaak et al. [26] | Poor Prognosis vs. Good Prognosis | Significance analysis of microarrays, Single sample gene set enrichment analysis, Kaplan-Meier curves, Log-rank test | Good or Poor prognosis, likelihood ratio =44.63 |
Obermayr et al. [27] | Disease-Free Survival, Overall Survival | Kaplan-Meier curves, Cox proportional hazards regression, χ2 test | ‘The presence of CTCs six months after completion of the adjuvant chemotherapy indicated relapse within the following six months with 41% sensitivity, and relapse within the entire observation period with 22% sensitivity (85% specificity)’ |
Han et al. [28] | Complete Response or Progressive Disease | Supervised principal component method | 349 gene signature: ROC AUC =0.702, p=0.022. 18 gene: ROC AUC =0.614, p=0.197. |
Hsu et al. [29] | Progression-Dree Survival | Semi-supervised hierarchical clustering | Good Response vs. Poor Response, p=0.021 |
Lui et al. [30] | Chemosensitivity, Overall Survival, Progression-Dree Survival | Predictive score using weighted voting algorithm, Kaplan-Meier curves, Log-rank Test, Cox proportional hazards regression | Response of 26 of 35 patients in an independent data set was correctly predicted, patients in the low-scoring group exhibited poorer PFS (HR=0.43, p=0.04), ROC AUC = 0.90(0.86–0.95) |
Kang et al. [31] | Overall Survival, Progression-Free Survival, Recurrence-Free Survival | Kaplan-Meier curves, Log-rank test, Cox proportional hazards regression, Pearson correlation coefficient | Berchuck dataset: HR=0.33, 95%CI=0.13–0.86, p=0.013; Tothill dataset: HR=0.61, 95%CI=0.36–0.99, p=0.044 |
Gillet et al. [32] | Overall Survival, Progression-Free Survival | Supervised principle components method, Cox proportional hazards regression, Kaplan-Meier curves, Log-rank test | ‘An 11-gene signature whose measured expression significantly improves the power of the covariates to predict poor survival’(p<0.003) |
Ferriss et al. [33] | Overall Survival | COXEN coefficient, Mann-Whitney U test, ROC analysis, Unsupervised Hierarchical Clustering | Carboplatin: sensitivity = 0.906, specificity = 0.174, PPV = 60%, NPV = 57% (UVA-55 validation set) |
Brun et al. [34] | 2-year Disease-Free Survival | Student’s T test, Principal component analysis, Concordance index, Kaplen-Meier curves, Log-rank test | No genes were found to have prognostic value |
Skirnisdottir and Seidal [35] | Recurrence, Disease-Free Survival | χ2 test, Kaplan-Meier curves, Log-rank test, Logistic regression, Cox proportional hazards regression | p53-status (OR=4.123, p=0.009; HR=2.447, p=0.019) was a significant and independent factor for tumor recurrence and DFS. |
Brenne et al. [36] | OC or MM, Progression-Free Survival, Overall Survival | Mann-Whitney U test, Kaplan-Meier curves, Log-rank test, Cox proportional hazards regression | Cox Multivariate Analysis: EHF mRNA expression in pre-chemotherapy effusions was an independent predictor of PFS (p=0.033, relative risk=4.528) |
Sabatier et al. [37] | Progression-Free Survival, Overall Survival | Cox proportional hazards regression, Pearson’s coefficient correlation score | Favourable vs. Unfavourable: ‘sensitivity = 61.6%, specificity = 62.4%, OR=2.7, 95%CI=1.7–4.2; p=6.1×10−06, Fisher’s exact test’ |
Gillet et al. [38] | Overall Survival, Progression-Free Survival, Treatment Response | Linear regression, Hierarchical clustering, Kaplan-Meier curves, Log-rank test | ‘6 gene signature alone can effectively predict the progression-free survival of women with ovarian serous carcinoma (log-rank p=0.002)’ |
Chao et al. [39] | Chemoresistance | Interaction and expression networks for pathway identification, pathway intersections, betweenness and degree centrality, Student’s T test | No statistical measure available. Many genes identified have previously been found experimentally |
Schlumbrecht et al. [40] | Overall Survival, Recurrence-Free Survival | Linear regression, Logistic regression, Cox proportional hazards regression, Kaplan-Meier curves, Unsupervised cluster analysis, Log-rank test, Mann-Whitney U test, χ2 test | ‘Greater EIG121 expression was associated with shorter time to recurrence (HR=1.13 (CI=1.02–1.26), p=0.021)’, ‘Increased expression of EIG121 demonstrated a statistically significant association with worse OS (HR=1.21 (CI1.09–1.35), p<0.001)’ |
Glaysher et al. [41] | Chemosensitivity | AIC gene selection, Multiple linear regression | Cisplatin: \(R^{2}_{\textit {adj}} = 0.836\), p<0.001 |
Yan et al. [42] | Chemosensitivity | ANOVA, Student’s T test, Mann-Whitney U test | ‘Immunostaining scores [Annexin A3] are significantly higher in platinum-resistant tumors (p=0.035)’ |
Yoshihara et al. [43] | Progression-Free Survival | Cox proportional hazards regression, Ridge regression, Prognostic index, ROC analysis, Kaplan-Meier curves, Log-rank test | ‘Prognostic index was an independent prognostic factor for PFS time (HR=1.64, p=0.0001)’, sensitivity = 64.4%, specificity = 69.2% |
Williams et al. [44] | Overall Survival | COXEN score, Kaplan-Meier curves, Student’s T test, ROC analysis, Spearman’s rank correlation coefficient, Logistic regression, Log-rank test | Carboplatin and Taxol: sensitivity = 77%, specificity = 56%, PPV=71%, NPV=78% |
Denkert et al. [45] | Overall Survival | Semi-supervised analysis via Cox scoring, Principal components analysis, Kaplan-Meier curves, Log-rank test, Cox proportional hazards regression | Duke et al.: ‘clinical outcome is significantly different depending on the OPI (p=0.021), with an HR of 1.7 (CI 1.1–2.6)’ |
Matsumura et al. [46] | Taxane sensitivity, Overall Survival | Hierarchical clustering, Kaplan-Meier curves, Log-rank test | ‘Patients in the YY1-High cluster who were treated with paclitaxel showed improved survival compared with the other groups (p=0.010)’ |
Crijns et al. [47] | Overall Survival | Supervised principal components method, Cox proportional hazards regression, Kaplan-Meier curves, Log-rank test, χ2 test | OSP: (High-risk vs. low-risk) HR=1.940, CI=1.190–3.163, p=0.008 |
Mendiola et al. [48] | Progression-Free Survival, Overall Survival | Kaplan-Meier curves, Log-rank test, AIC-based model selection, ROC curves, Cox proportional hazards regression | OS: sensitivity = 87.2%, specificity = 86.4% |
Gevaert et al. [49] | Platin Resistance/Sensitivity, Stage | Principal component analysis, Least squares support vector machines | Platin-Resistance/Sensitivity: sensitivity = 67%, specificity = 40%, accuracy = 51.11% |
Bachvarov et al. [50] | Chemoresistance | Hierarchical Clustering, Support vector machines | No prediction metric applied |
Netinatsunthorn et al. [51] | Overall Survival, Recurrence-Free Survival | Kaplan-Meier curves, Cox proportional hazards regression | OS: HR=1.98, 95%CI=1.28–3.79, p=0.0138 ; RFS: HR=3.36, 95%CI=1.60–7.03, p=0.0017 |
De Smet et al. [52] | Stage I vs. Advanced stage, Platin-sensistive vs. Platin-resistant | Principal component analysis, Least squares support vector machines | Estimated Classification Accuracy: Stage I vs Advanced Stage =100%, Platin-sensitive vs. Platin-resistant =76.9% |
Helleman et al. [53] | Chemoresponse (responder vs. non-responder) | Class prediction, Hierarchical clustering, Principal component analysis | Test set: PPV=24%, NPV=97%, sensitivity =89%, specificity =59% |
Spentzos et al. [54] | Chemoresponse (pathological-CR or PD), Disease-Free survival, Overall Survival | Class prediction analysis, Compound covariate algorithm, Average linkage hierarchical clustering, Kaplan-Meier curves, Log-rank test, Cox proportional hazards regression | Cox PH (resistant vs. sensitive): Recurrence HR=2.7 (95%CI=1.2–6.1), Death HR=3.9 (95%CI=3.1–11.4) |
Jazaeri et al. [55] | Clinical response | Class prediction | 9 most significantly differentially expressed genes, primary chemoresistant vs. primary chemosensitive: accuracy =77.8% |
Raspollini et al. [56] | Overall Survival (high vs. low) | Univariate logistic regression, χ2 test | COX-2: OR=0.23, 95%CI=0.06–0.77, p=0.017; MDR1: OR=0.01, 95%CI=0.002–0.09, p=<0.0005 |
Hartmann et al. [57] | Time To Relapse (early vs.late) | Support vector machine, Kaplan-Meier curves, Log-rank test, average linkage clustering | Accuracy =86%, PPV=95%, NPV=67% |
Spentzos et al. [58] | Disease-Free Survival, Overall Survival | Supervised pattern recognition/class prediction, Kaplan-Meier curves, Log-rank test, Cox proportional hazards regression | Unfavourable vs. Favourable OS : (CPH) HR=4.6, 95%CI=2.0–10.7, p=0.0001 |
Selvanayagam et al. [59] | Chemoresistance (chemoresistant vs. chemosensitive) | Supervised voice-pattern recognition algorithm (clustering) | PPV=1, NPV=1 |
Iba et al. [60] | Chemoresponse, Overall Survival | Kaplan-Meier curves, Log-rank test, Cox propotionate hazards regression, ROC analysis, χ2 test, Student’s T test, Mann-Whitney U test | ‘Patients with c-myc expression of over 200 showed a significantly better 5-year survival rate (69.8% vs. 43.5%)’, p<0.05 |
Kamazawa et al. [61] | Chemoresponse (CR or PR vs. NC or PD) | Defined threshold expressionto divide responders and non-responders | MDR-1 (all samples): specificity =95%, sensitivity = 100%, predictive value =96% |
Vogt et al. [62] | Chemoresistance | Correlation of AUC from in-vitro ATP-CVA and gene expression | All p values for correlation of drugs and genes were >0.05 |
Tissue source
mRNA source | Number of studies |
---|---|
FFPE tissue | 12 |
Fresh-frozen tissue | 22 |
Fresh-frozen effusion | 2 |
Fresh tissue | 1 |
Blood | 1 |
Not used | 9 |
Not specified | 2 |
Gene or protein expression quantification
Histology
Chemotherapy
End-point to be predicted
Model development
Technique | Number of papers |
---|---|
Cox proportional hazards regression | 17 |
Hierarchical clustering | 11 |
Principal components analysis | 8 |
Student’s T test | 7 |
Scoring algorithm | 6 |
Support Vector Machines | 5 |
Correlation coefficients | 5 |
Mann-Whitney U test | 5 |
χ2 test | 5 |
ROC analysis | 5 |
Class prediction | 4 |
Logistic regression | 3 |
Linear regression | 3 |
AIC gene selection | 2 |
Concordance index | 1 |
Pathway interaction networks | 1 |
ANOVA | 1 |
Expression threshold identified | 1 |
Gene set enrichment analysis | 1 |
Linear discriminant analysis | 1 |
ISIS bipartitoning | 1 |
Gaussian mixture modelling | 1 |
Significance analysis of microarrays | 1 |
Ridge regression | 1 |
Genes identified
Number of papers | Number of genes | Percent of genes |
---|---|---|
identifying a gene | ||
1 | 1214 | 93.53% |
2 | 78 | 6.01% |
3 | 5 | 0.385% |
4 | 1 | 0.08% |
A1BG | CHPF2 | FSCN1 | LRRC16B | PKD1 | SOBP |
A2M | CHRDL1 | FXYD6 | LRRC17 | PKHD1 | SORBS3 |
AADAC | CHRNE | FZD4 | LRRC59 | PLA2G7 | SOS1 |
AAK1 | CHST6 | FZD5 | LRSAM1 | PLAA | SOX12 |
ABCA13 | CHTOP | G0S2 | LSAMP | PLAU | SOX21 |
ABCA4 | CIAPIN1 | G3BP1 | LSM14A | PLAUR | SPANXD |
ABCB1 | CIB1 | GABRP | LSM3 | PLCB3 | SPATA13 |
ABCB10 | CIB2 | GAD1 | LSM7 | PLEC | SPATA18 |
ABCB11 | CIITA | GALNT10 | LSM8 | PLEK | SPATA4 |
ABCB7 | CILP | GAP43 | LTA4H | PLIN2 | SPC25 |
ABCC3 | CITED2 | GART | LTB | PLS1 | SPDEF |
ABCC5 | CKLF | GATAD2A | LTK | PMM1 | SPEN |
ABCD2 | CLCA1 | GCH1 | LUC7L2 | PMP22 | SPHK2 |
ABCG2 | CLCNKB | GCHFR | LY6K | PMVK | SPOCK2 |
ABLIM1 | CLDN10 | GCM1 | LY96 | PNLDC1 | SPTBN2 |
ACADVL | CLIP1 | GDF6 | LZTFL1 | PNLIPRP2 | SRC |
ACAT2 | CNDP1 | GFRA1 | MAB21L2 | PNMA5 | SREBF2 |
ACKR2 | CNKSR3 | GGCT | MAD2L2 | POFUT2 | SRF |
ACKR3 | CNN2 | GGT1 | MAGEE2 | POLH | SRRM1 |
ACO2 | CNOT8 | GJB1 | MAGEF1 | POLR3K | SRSF3 |
ACOT13 | CNTFR | GLRX | MAK | POMP | SSR1 |
ACP1 | cofilin1 | GMFB | MAMLD1 | POU2AF1 | SSR2 |
ACRV1 | COL10A1 | GMPR | MANF | POU5F1 | SSUH2 |
ACSM1 | COL21A1 | GNA11 | MAP6D1 | PPAP2B | SSX2IP |
ACSS3 | COL3A1 | GNAO1 | MAPK1 | PPAT | ST6GALNAC1 |
ACTA2 | COL4A4 | GNAZ | MAPK1IP1L | PPCDC | STC2 |
ACTB | COL4A6 | GNG4 | MAPK3 | PPCS | STK38 |
ACTBL3 | COL6A1 | GNG7 | MAPK8IP3 | PPFIA3 | STX12 |
ACTG2 | COL7A1 | GNL2 | MAPK9 | PPIC | STX1B |
ACTR3B | COX8A | GNMT | MAPKAP1 | PPIE | STX7 |
ACTR6 | CPD | GNPDA1 | MAPKAPK2 | PPP1R1A | STXBP2 |
ADAMDEC1 | CPE | GOLPH3 | MARCKS | PPP1R1B | STXBP6 |
ADAMTS5 | CPEB1 | GPIHBP1 | MARK4 | PPP1R2 | SUB1 |
ADIPOR2 | CRCT1 | GPM6B | MATK | PPP1R26 | SULT1C2 |
ADK | CREB5 | GPR137 | MB | PPP2R3C | SULT2B1 |
AEBP1 | CRYAB | GPT2 | MBOAT7 | PPP2R5C | SUPT5H |
AF050199 | CRYBB1 | GPX2 | MCF2L | PPP2R5D | SUSD4 |
AF052172 | CRYL1 | GPX3 | MCL1 | PPP4R4 | SUV420H1 |
AFM | CRYM | GPX8 | MCM3 | PPP6R1 | SV2C |
AFTPH | CSE1L | GRAMD1B | MDC1 | PRAP1 | SYNM |
AGFG1 | CSPP1 | GRB2 | MDFI | PRELP | SYT1 |
AGR2
| CSRP1 | GRK6 | MDK | PRKAB1 | SYT11 |
AGT | CSRP3 | GRM2 | MDR-1 | PRKCH | SYT13 |
AIPL1 | CST6 | GRPEL1 | MEA1 | PRKCI | TAC3 |
AKAP12
| CST9L | GRSF1 | MEAF6 | PRKD3 | TAP1 |
AKR1A1 | CT45A6 | GSPT1 | MECOM | PROC | TASP1 |
AKR1C1 | CTA-246H3.1 | GSTM2 | MEF2B | PROK1 | TBCC |
AKT1 | CTNNBL1 | GSTT1 | MEGF11 | PRPF31 | TBP |
AKT2 | CTSD | GTF2E1 | MEST | PRRX1 | TCF15 |
ALCAM | CUTA | GTF2F2 | METRN | PRSS16 | TCF7L2 |
ALDH5A1 | CX3CL1 | GTF2H5 | METTL13 | PRSS22 | TENM3 |
ALDH9A1 | CXCL1 | GTPBP4 | METTL4 | PRSS3 | TEX30 |
ALG5 | CXCL10 | GUCY1B3 | MFAP2 | PRSS36 | TFF1 |
ALMS1 | CXCL12 | GYG1 | MFSD7 | PSAT1 | TFF3 |
AMPD1 | CXCL13 | GYPC | MGMT | PSMB5 | TFPI2 |
ANKHD1 | CXCR4 | GZMB | MINOS1 | PSMB9 | TGFB1 |
ANKRD27 | CYB5B | GZMK | MKRN1 | PSMC4 | THBS4 |
ANXA3 | CYBRD1 | H2AFX | MLF2 | PSMD1 | TIAM1 |
ANXA4 | CYP27A1 | H3F3A | MLH1 | PSMD12 | TIMM10B |
AOC1 | CYP2E1 | HAP1 | MLX | PSMD14 | TIMM17B |
AP2A2 | CYP3A7 | HBG2 | MMP1 | PSME4 | TIMP1 |
APC | CYP4X1 | HDAC1 | MMP10 | PTBP1 | TIMP2 |
API5 | CYP4Z1 | HDAC2 | MMP12 | PTCH2 | TIMP3 |
APOE | CYP51A1 | HECTD4 | MMP13 | PTEN | TKTL1 |
AQP10 | CYSTM1 | HES1 | MMP16 | PTGDS | TLE2 |
AQP5 | CYTH3 | HEY1 | MMP17 | PTGS2 | TM9SF2 |
AQP6 | D4S234E | HHIPL2 | MMP3 | PTP4A1 | TM9SF3 |
AQP9 | DAP | HIF1A | MMP7 | PTP4A2 | TMCC1 |
ARAF | DAPL1 | HIP1R | MMP9 | PTPRN2 | TMED5 |
ARAP1 | DBI | HIPK1 | MPZL1 | PTPRS | TMEM139 |
AREG | DCBLD2 | HIST1H1C | MRPL2 | PWP2 | TMEM14B |
ARFGEF2 | DCHS1 | HK2 | MRPL35 | QPRT | TMEM150A |
ARHGAP29 | DCK | HLAA | MRPL49 | R3HDM2 | TMEM161A |
ARHGDIA | DCTN5 | HLADMB | MRPS12 | RAB26 | TMEM259 |
ARL14 | DCTPP1 | HLADOB | MRPS17 | RAB27B | TMEM260 |
ARL6IP4 | DCUN1D4 | HMBOX1 | MRPS24 | RAB40B | TMEM45A |
ARMC1 | DCUN1D5 | HMGCS1 | MRPS9 | RAB5B | TMEM50A |
ARNT2 | DDB1 | HMGCS2 | MRS2 | RAB5C | TMPRSS3 |
ARPC4 | DDB2 | HMGN1 | MSH2 | RABIF | TMSB15B |
ASAP1 | DDR1 | HMOX2 | MSL1 | RAC1 | TMTC1 |
ASAP3 | DDX23 | HNRNPA1 | MSMO1 | RAC3 | TMX2 |
ASF1A | DDX49 | HNRNPUL2 | MST1 | RAD23A | TNFRSF17 |
ASIP | DEFB132 | HOPX | MT1G | RAD51 | TNS1 |
ASPA | DERL1 | HOXA5 | MTCP1 | RAD51AP1 | TOMM40 |
ASPHD1 | DFNB31 | HOXB6 | MTMR11 | RANBP1 | TONSL |
ASS1 | DHCR7 | HPN | MTMR2 | RANGAP1 | TOP1 |
ASUN | DHRS11 | HRASLS | MTPAP | RARRES2 |
TOP2A
|
ATM | DHRS9 | Hs.120332 | MTUS1 | RB1 | TOX3 |
ATP1B3 | DHX15 | HS3ST1 | MTX1 | RBBP7 |
TP53
|
ATP5D | DHX29 | HS3ST5 | MUS81 | RBFA | TP53TG5 |
ATP5F1 | DIAPH3 | HSD11B2 |
MUTYH
| RBM11 | TP73 |
ATP5L | DICER1 | HSD17B11 | MXD1 | RBM39 | TPD52 |
ATP6V0E1 | DIRC1 | HSPA1L | MXI1 | RCHY1 | TPM2 |
ATP7B | DKK1 | HSPA4 | MYBPC1 | RER1 | TPP2 |
ATP8A2 | DLAT | HSPA8 | MYC | RFC3 | TPPP |
AUP1 | DLEU2 | HSPB7 | MYCBP | RGL2 | TPRKB |
AURKA | DLG1 | HSPD1 | MYL9 | RGP1 | TRA |
AURKC | DLG3 | HTATIP2 | MYO1D | RGS19 | TRAF3IP2 |
AVIL | DLGAP4 | HTN1 | MYOM1 | RHOT1 | TRAM1 |
B3GALNT1 | DLGAP5 | HTR3A | NANOS1 | RHPN2 | TRAPPC4 |
B3GNT2 | DMRT3 | ICAM1 | NASP | RIIAD1 | TRAPPC9 |
B4GALT5 | DNAH2 | ICAM5 | NBEA | RIN1 | TREML1 |
BAG3 | DNAH7 | ID1 | NBL1 | RIT1 | TREML2 |
BAIAP2L1 | DNAJB12 | ID4 | NBN | RNF10 | TRIAP1 |
BAK1 | DNAJB5 | IDI1 | NCAM1 | RNF13 | TRIM27 |
BASP1 | DNAJC16 | IFIT1 | NCAPD2 | RNF14 | TRIM49 |
BAX | DNASE1L3 | IGF1R | NCAPG | RNF148 | TRIM58 |
BCHE | DOCK3 | IGFBP2 | NCAPH | RNF34 | TRIML2 |
BCL2A1 | DPH2 | IGFBP5 | NCKAP5 | RNF6 | TRIT1 |
BCL2L11 | DPM1 | IGHM | NCOA1 | RNF7 | TRMT1L |
BCL2L12 | DPP7 | IGKC | NCOR2 | RNF8 | TRO |
BCR-ABL | DPYSL2 | IGKV1-5 | NCR2 | RNGTT | TRPV4 |
BEAN | DRD4 | IHH | NCSTN | RNPEPL1 | TRPV6 |
BEST4 | DTYMK | IKZF4 | NDRG2 | ROBO1 | TSPAN3 |
BFSP1 | DUSP2 | IL11RA | NDST1 | ROR1 | TSPAN4 |
BFSP2 | DUSP4 | IL15 | NDUFA12 | ROR2 | TSPAN6 |
BGN | DUX3 | IL17RB | NDUFA9 | RP13-347D8.3 | TSPAN7 |
BHLHE40 | DYNLT1 | IL1B | NDUFAB1 | RP13-36C9.6 | TSR1 |
BIN1 | DYRK3 | IL23A | NDUFAF4 | RPA3 | TTC31 |
BIRC5 | E2F2 | IL27 | NDUFB4 | RPL23 | TTLL6 |
BIRC6 | ECH1 | IL6 | NDUFS5 | RPL29P17 | TTPAL |
BLCAP | EDF1 | IL8 | NEBL | RPL31 | TTYH1 |
BLMH | EDN1 | IMPA2 | NETO2 | RPL36 | TUBB3 |
BMP8B | EDNRA | ING3 | NEUROD2 | RPP30 | TUBB4A |
BMPR1A | EDNRB | INHBA | NFE2 | RPS15 | TUBB4Q |
BNIP3 | EEF1A2 | INPP5A | NFE2L3 | RPS16 | TUSC3 |
BOLA3 | EFCAB14 | INPP5B | NFIB | RPS19BP1 | UBD |
BPTF | EFEMP2 | INSR | NFKBIB | RPS24 | UBE2I |
BRCA1 | EFNB2 | INTS12 | NFS1 | RPS28 | UBE2K |
BRCA2 | EGF | INTS9 | NID1 | RPS4Y1 | UBE2L3 |
BRSK1 | EGFR | IRF2BP1 | NIT1 | RPS6KA2 | UBE4B |
BTN3A3 | EHD1 | ISCA1 | NKIRAS2 | RPSA | UBR5 |
BTNL9 | EHF | ISG20 | NKX31 | RRAGC | UGT2B17 |
C11orf16 | EI24 | ITGAE | NKX62 | RRBP1 | UGT8 |
C11orf74 | EIF1 | ITGB2 | NLGN1 | RRN3 | UHRF1BP1 |
C12orf5 | EIF2AK2 | ITGB6 | NOP5/58 | RSL24D1 | UMOD |
C16orf89 | EIF3K | ITGB7 | NOS3 | RSU1 | UPK1A |
C17orf45 | EIF4E2 | ITLN1 | NOTCH4 | RTN4R | UPK1B |
C17orf53 | EIF5 | ITM2A | NOV | RXRB | UQCRC2 |
C17orf70 | ELF3 | ITM2C | NOX1 | RYBP | URI1 |
C1orf109 | ELF5 | ITPR2 | NPAS3 | RYR3 | USP14 |
C1orf115 | EML4 | ITPRIP | NPR1 | S100A10 | USP18 |
C1orf159 | ENC1 | JAG2 | NPR3 | S100A4 | USP21 |
C1orf198 | ENOPH1 | JAK2 | NPTX2 | S100P | UST |
C1orf27 | ENSA | JAKMIP2 | NPTXR | SAMD4B | UTP11L |
C1orf68 | ENTPD4 | KCNB1 | NPY | SASH1 | UTP20 |
C1QTNF3 | EPB41L4A | KCNE3 | NRBP2 | SCAMP3 | UVRAG |
C20orf199 | EPCAM | KCNH2 | NRG4 | SCARF1 | VDR |
C2orf72 | EPHB2 | KCNJ16 | NRP1 | SCG2 | VEGFA |
C4A | EPHB3 | KCNN1 | NSFL1C | SCGB1C1 | VEGFB |
C4BPA | EPHB4 | KCNN3 | NSL1 | SCGB3A1 | VEZF1 |
C6orf120 | EPOR | KCTD1 | NSMCE4A | SCNM1 | VPS39 |
C6orf124 | ERBB3 | KCTD5 | NT5C3A | SCO2 | VPS52 |
C9orf3 | ERCC8 | KDELC1 | NTAN1 | SCUBE2 | VPS72 |
C9orf47 | ERMP1 | KDELR1 | NTF4 | SDF2L1 | VTCN1 |
CA13 | ESF1 | KDELR2 | NUDT21 | SEC14L2 | VTI1B |
CACNA1B | ESM1 | KDM4A | NUDT9 | SELT | WBP2 |
CACNG6 | ESR1 | Ki67 | NUS1 | SEMA3A | WBP4 |
CADM1 | ESRP2 | KIAA0125 | OAS3 | SENP3 | WDR12 |
CALML3 | ESYT1 | KIAA0141 | OASL | SENP6 | WDR45B |
CAMK2B | ETS1 | KIAA0226 | ODF4 | SEPN1 | WDR7 |
CAMK2N1 | ETV1 | KIAA0368 | OGFOD3 | SERPINB6 | WDR77 |
CANX | EVA1A | KIAA1009 | OGN | SERPIND1 | WIT1 |
CAP1 | EXOC6B | KIAA1033 | OPA3 | SERPINF1 | WIZ |
CAP2 | EXTL1 | KIAA1324 | OR10A3 | SERTAD4 | WNK4 |
CAPN13 | EYA2 | KIAA1551 | OR2AG1 | SETBP1 | WNT16 |
CAPN5 | F2R | KIAA2022 | OR4C15 | SF3A3 | WT1 |
CASC3 | FAAH | KIAA4146 | OR51B5 | SF3B4 | WTAP |
CASP9 | FABP1 | KIF3A | OR51I1 | SGCB | WWOX |
CASS4 | FABP7 | KIFC3 | OR6F1 | SGCG | XBP1 |
CATSPERD | FADS1 | KIT | OR9G9 | SGPP1 | XPA |
CC2D1A | FADS2 | KLF12 | OSGEPL1 | SH3PXD2A | XPO4 |
CCBL1 | FAM133A | KLF5 | OSGIN2 | SHFM1 | XYLT1 |
CCDC130 | FAM135A | KLHDC3 | OSM | SHOX | Y09846 |
CCDC135 | FAM155B | KLHL7 | OXTR | SIDT1 | YBX1 |
CCDC147 | FAM174B | KLK10 | P2RX4 | SIGLEC8 | YIPF3 |
CCDC167 | FAM19A4 | KLK6 | PABPC4 | SIRT5 | YIPF6 |
CCDC19 | FAM211B | KPNA3 | PAGR1 | SIRT6 | YLPM1 |
CCDC53 | FAM217B | KPNA6 | PAH | SIVA1 | YWHAE |
CCDC9 | FAM49B | KRT10 | PAK4 | SIX2 | YWHAZ |
CCL13 | FAM8A1 | KRT12 | PALB2 | SKA3 | ZBTB11 |
CCL2 | FANCB | KYNU | PARD6B | SLAMF7 | ZBTB16 |
CCL28 | FANCE | L1TD1 | PAX6 | SLC12A2 | ZBTB8A |
CCM2L | FANCF | LAMB1 | PBK | SLC12A4 | ZC3H13 |
CCNA2 | FANCG | LAMTOR5 | PBX2 | SLC14A1 | ZCCHC8 |
CCNG2 | FANCI | LARP4 | PBXIP1 | SLC15A2 | ZEB2 |
CCT6A | FARP1 | LAX1 | PCF11 | SLC1A1 | ZFHX4 |
CCZ1 | FAS | LAYN | PCGF3 | SLC1A3 | ZFP91 |
CD34 | FASLG | LBR | PCK1 | SLC22A5 | ZFR2 |
CD38 | FBXL18 | LCMT2 | PCNA | SLC25A37 | ZKSCAN7 |
CD44 | FCGBP | LCTL | PCNXL2 | SLC25A41 | ZMYND11 |
CD46 | FCGR3B | LDB1 | PCOLCE | SLC25A5 | ZNF106 |
CD70 | FEN1 | LDHB | PCSK6 | SLC26A9 | ZNF12 |
CD97 | FEZ1 | LGALS4 | PDCD2 | SLC27A6 | ZNF124 |
CDC42EP4 | FGF2 | LGR5 | PDE3A | SLC29A1 | ZNF148 |
CDCA2 | FGFBP1 | LHB | PDGFA | SLC2A1 | ZNF155 |
CDH12 | FGFR1OP | LHX1 | PDGFRA | SLC2A5 | ZNF180 |
CDH19 | FGFR1OP2 | LIN28A | PDGFRB | SLC37A4 | ZNF200 |
CDH3 | FGFR2 | LINGO1 | PDP1 | SLC39A2 | ZNF292 |
CDH4 | FHL2 | LIPA | PDSS1 | SLC4A11 | ZNF337 |
CDH5 | FILIP1 | LIPC | PDZK1 | SLC5A1 | ZNF432 |
CDK17 | FJX1 | LIPG | PEBP1 | SLC5A3 | ZNF467 |
CDK20 | FKBP11 | LMO3 | PEX11A | SLC5A5 | ZNF48 |
CDK5R1 | FKBP1B | LMO4 | PEX6 | SLC6A3 | ZNF503 |
CDK8 | FKBP7 | LOC100129250 | PFAS | SLC7A2 | ZNF521 |
CDKN1A | FLII | LOC149018 | PGAM1 | SMAD2 | ZNF569 |
CDY1 | FLJ41501 | LOC1720 | PHF3 | SMC4 | ZNF644 |
CDYL2 | FLNC | LOC389677 | PHGDH | SMG1 | ZNF71 |
CEACAM5 | FLOT2 | LOC642236 | PHKA1 | SMPD2 | ZNF711 |
CEACAM6 | FLT1 | LOC646808 | PHKA2 | SNIP1 | ZNF74 |
CEACAM7 | FMN2 | LOC90925 | PI3 | SNRPA1 | ZNF76 |
CEP55 | FMO1 | LPAR6 | PIC3CD | SNRPC | ZNF780B |
CES1 | FN1 | LPCAT2 | PIGC | SNRPD3 | ZYG11A |
CES2 |
FOXA2
| LPCAT4 | PIGR | SNX13 | |
CFI | FOXD4L2 | LPHN2 | PIK3CG | SNX19 | |
CH25H | FOXJ1 | LRIG1 | PIP5K1B | SNX7 | |
CHIT1 | FOXO3 | LRIT1 | PITRM1 | SOAT2 |
Gene symbol | Number of studies | Function | Expression links to cancer in literature |
---|---|---|---|
AGR2 | 4 | Cell migration and growth | Prostate, breast, ovarian, pancreatic |
MUTYH | 3 | Oxidative DNA damage repair | Colorectal |
AKAP12 | 3 | Subcellular compartmentation of PKA | Colorectal, lung, prostate |
TP53 | 3 | Cell cycle regulation | Breast |
TOP2A | 3 | Required for DNA replication | Breast, prostate, ovarian |
FOXA2 | 3 | Liver-specific transcription factor | Lung, prostate |
SRC | 2 | Regulation of cell growth | Colon, liver, lung, breast, pancreatic |
SIVA1 | 2 | Pro-apoptotic protein | Many cancers |
ALDH9A1 | 2 | Aldehyde dehydrogenase | Many cancers |
LGR5 | 2 | Associated with stem cells | Cancer stem cells |
EHF | 2 | Epithelial differentiation and proliferation | Prostate |
BAX | 2 | Apoptotic activator | Colon, breast, prostate, gastric, leukaemia |
CES2 | 2 | Intestine drug clearance | Colorectal |
CPE | 2 | Synthesis of hormones and neurotransmitters | |
FGFBP1 | 2 | Cell proliferation, differentiation and migration | Colorectal, pancreatic |
TUBB4A | 2 | Component of microtubules | |
ZNF12 | 2 | Transcription regulation | |
RBM39 | 2 | Steroid hormone receptor-mediated transcription | |
RFC3 | 2 | Required for DNA replication | |
GNPDA1 | 2 | Triggers calcium oscillations in mammalian eggs | |
ANXA3 | 2 | Regulation of cellular growth | Prostate, ovarian |
NFIB | 2 | Activates transcription and replication | Breast |
ACTR3B | 2 | Actin cyctoskeleton organisation | Lung |
YWHAE | 2 | Mediates signal transduction | Lung, endometrial |
CYP51A1 | 2 | Drug metabolism and lipid synthesis | |
HMGCS1 | 2 | Cholesterol synthesis and ketogenesis | |
ZMYND11 | 2 | Transcriptional repressor | |
FADS2 | 2 | Regulates unsaturation of fatty acids | |
SNX7 | 2 | Family involved in intracellular trafficking | |
ARHGDIA | 2 | Regulates the GDP/GTP exchange reaction of the Rho proteins | Prostate, lung, |
NDST1 | 2 | Inflammatory response | Prostate, breast |
AOC1 | 2 | Catalyses degredation of such as histamine and spermidine | |
DAP | 2 | Positive mediator of programmed cell death | |
ERCC8 | 2 | Transcription-coupled nucleotide excision repair | |
GUCY1B3 | 2 | Catalyzes conversion of GTP to the second messenger cGMP | |
HDAC1 | 2 | Control of cell proliferation and differentiation | Prostate, breast, colorectal, gastric |
HDAC2 | 2 | Transcriptional regulation and cell cycle progression | Cervical, gastric, colorectal |
IGFBP5 | 2 | Cell proliferation, differentiation, survival, and motility | Breast |
IL6 | 2 | Transcriptional inflammatory response, B cell maturation | Many cancers |
LSAMP | 2 | Neuronal surface glycoprotein | Osteosarcoma |
MDK | 2 | Cell growth, migration, angiogenesis | Many cancers |
MYCBP | 2 | Stimulates the activation of E box-dependent transcription | |
S100A10 | 2 | Transport of neurotransmitters | Colorectal, lung, breast |
SLC1A3 | 2 | Glutamate transporter | |
NCOA1 | 2 | Stimulates hormone-dependent transcription | Breast, prostate |
TIAM1 | 2 | Modulates the activity of Rho GTP-binding proteins | Many cancers |
VEGFA | 2 | Angiogenesis, cell growth, cell migration, apoptosis | Many cancers |
RPL36 | 2 | Component of ribosomal 60S subunit | |
LBR | 2 | Anchors lamina and heterochromatin to the nuclear membrane | |
ABCB1 | 2 | ATP-dependent drug efflux pump for xenobiotic compounds | Many cancers |
FASLG | 2 | Required for triggering apoptosis in some cell types | Many cancers |
TIMP1 | 2 | Extracellular matrix, proliferation, apoptosis | Many cancers |
FN1 | 2 | Cell adhesion, motility, migration processes | Many cancers |
TGFB1 | 2 | Proliferation, differentiation, adhesion, migration | Prostate, breast, colon, lung, bladder |
XPA | 2 | DNA excision repair | Many cancers |
ABCB10 | 2 | Mitochondrial ATP-binding cassette transporter | |
POLH | 2 | Polymerase capable of replicating UV-damaged DNA for repair | |
ITGAE | 2 | Adhesion, intestinal intraepithelial lymphocyte activation | |
ZNF200 | 2 | Zinc finger protein | |
COL3A1 | 2 | Collagen type III, occurring in most soft connective tissues | |
ACKR3 | 2 | G-protein coupled receptor | |
EPHB3 | 2 | Mediates developmental processes | Lung, colorectal |
NBN | 2 | Double-strand DNA repair, cell cycle control | |
PCF11 | 2 | May be involved in Pol II release following polymerisation | |
DFNB31 | 2 | Sterocilia elongation, actin cystoskeletal assembly | |
BRCA2 | 2 | Double-strand DNA repair | Breast, ovarian |
AADAC | 2 | Arylacetamide deacetylase | |
CD38 | 2 | Glucose-induced insulin secretion | Leukaemia |
CHIT1 | 2 | Involved in degradation of chitin-containing pathogens | |
CXCR4 | 2 | Receptor specific for stromal-derived-factor-1 | Breast, glioma, kidney, prostate |
EFNB2 | 2 | Mediates developmental processes | |
MECOM | 2 | Apoptosis, development, cell differentiation, proliferation | Leukaemia |
FILIP1 | 2 | Controls neocortical cell migration | Ovarian |
HSPB7 | 2 | Heat shock protein | |
LRIG1 | 2 | Regulator of signaling by receptor tyrosine kinases | Glioma |
MMP1 | 2 | Breakdown of extracellular matrix | Gastric, breast |
PSAT1 | 2 | Phosphoserine aminotransferase | |
SDF2L1 | 2 | Part of endoplasmic reticulum chaperone complex | |
TCF15 | 2 | Regulation of patterning of the mesoderm | |
EPHB2 | 2 | Contact-dependent bidirectional signaling between cells | Colorectal |
ETS1 | 2 | Involved in stem cell development, cell senescence and death | Many cancers |
TRIM27 | 2 | Male germ cell differentiation | Ovarian, endometrial, prostate |
MARK4 | 2 | Mitosis, cell cycle control | Glioma |
B4GALT5 | 2 | Biosynthesis of glycoconjugates and saccharides |
Gene set enrichment
Model predictive ability
Sensitivity and specificity
Study | Prediction | Sensitivity | Specificity | LR+ve
†
| LR-ve
†
| P(C+)
†
| P(C−)
†
| P(C+|T+)
†
| P(C+|T−)
†
|
---|---|---|---|---|---|---|---|---|---|
Li et al. [3] | Chemoresistance | 0.96* | 0.23* | 1.24 | 0.18 |
\(\frac {22}{44}\)
|
\(\frac {22}{44}\)
| 0.55 | 0.15 |
Obermayr et al. [27] | RFS | 0.22* | 0.85* | 1.47 | 0.92 |
\(\frac {46}{216}\)
|
\(\frac {170}{216}\)
| 0.28 | 0.77 |
Ferriss et al. [33] | Chemoresponse | 0.94* | 0.29* | 1.33 | 0.20 |
\(\frac {85}{119}\)
|
\(\frac {34}{119}\)
| 0.77 | 0.07 |
Sabatier et al. [37] | Prognosis | 0.62* | 0.62* | 1.64 | 0.62 |
\(\frac {194}{366}\)
|
\(\frac {172}{366}\)
| 0.65 | 0.35 |
Yoshihara et al. [43] | PFS | 0.64* | 0.69* | 2.06 | 0.52 |
\(\frac {45}{87}\)
|
\(\frac {39}{87}\)
| 0.69 | 0.30 |
Williams et al. [44] | Prognosis | 0.77* | 0.56* | 1.75 | 0.41 |
\(\frac {97}{143}\)
|
\(\frac {46}{143}\)
| 0.79 | 0.16 |
Gevaert et al. [49] | Chemoresistance | 0.67* | 0.40* | 1.12 | 0.82 |
\(\frac {15}{45}\)
|
\(\frac {30}{45}\)
| 0.36 | 0.62 |
Helleman et al. [53] | Chemoresistance | 0.89* | 0.56* | 2.02 | 0.20 |
\(\frac {9}{72}\)
|
\(\frac {63}{72}\)
| 0.22 | 0.58 |
De Smet et al. [52] | Chemoresistance | 0.71
†
| 0.83
†
| 4.29 | 0.34 |
\(\frac {6}{13}\)
|
\(\frac {7}{13}\)
| 0.79 | 0.29 |
Raspollini et al. [56] | Prognosis | 0.79
†
| 0.46
†
| 1.45 | 0.47 |
\(\frac {28}{52}\)
|
\(\frac {24}{52}\)
| 0.63 | 0.29 |
Hartmann et al. [57] | Prognosis | 0.86* | 0.86* | 6.14 | 0.16 |
\(\frac {21}{28}\)
|
\(\frac {7}{28}\)
| 0.95 | 0.05 |
Selvanayagam et al. [59] | Chemoresistance | 1.00
†
| 1.00
†
|
∞
| 0.00 |
\(\frac {4}{8}\)
|
\(\frac {4}{8}\)
| 1.00 | 0.00 |
Kamazawa et al. [61] | Chemoresponse | 1.00* | 0.83
†
| 6.00 | 0.00 |
\(\frac {21}{27}\)
|
\(\frac {5}{27}\)
| 0.95 | 0.00 |
Hazard ratios
Study | Prediction | Classes | HR | 95% CI | Median survival | P value |
---|---|---|---|---|---|---|
Jeong et al. [22] | OS | YA subgroup vs. YI subgroup | 0.5 | 0.31−0.82 | 0.005 | |
Roque et al. [24] | OS | High vs. low TUBB3 staining | 3.66 | 1.11−12.05 | 707 days vs. not reached | 0.03 |
Kang et al. [31] | OS | High vs. low score | 0.33 | 0.13−0.86 | 1.8 years vs. 2.9 years | <0.001 |
Skirnisdottir and Seidal [35] | Recurrence | p53 -ve vs. +ve | 4.12 | 1.41−12.03 | 0.009 | |
Schlumbrecht et al. [40] | RFS | EIG121 high vs. low | 1.13 | 1.02−1.26 | 0.021 | |
Yoshihara et al. [43] | PFS | High vs. low score | 1.64 | 1.27−2.13 | 0.0001 | |
Denkert et al. [45] | OS | Low vs. high score | 1.7 | 1.1−2.6 | 0.021 | |
Crijns et. al [47] | OS | 1.94 | 1.19−3.16 | 0.008 | ||
Netinatsunthorn et al. [51] | RFS | Yes vs. no WT1 staining | 3.36 | 1.60−7.03 | 0.0017 | |
Spentzos et al. [54] | OS | Resistant vs. sensitive | 3.9 | 1.3−11.4 | 41 months vs. not reached | <0.001
†
|
Raspollini et al. [56] | OS | No vs. yes COX-2 staining | 0.23 | 0.06−0.77 | 0.017 | |
Spentzos et al. [58] | OS | High vs. low score | 4.6 | 2.0−10.7 | 30 months vs. not reached | 0.0001 |