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Journal of Cancer Research and Clinical Oncology

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12.06.2018 | Original Article – Cancer Research

Association between pathologic factors and ERG expression in prostate cancer: finding pivotal networking

verfasst von: Seung-Ryeol Lee, Young-Deuk Choi, Nam-Hoon Cho

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2018

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Abstract

Purpose

To evaluate associations between pathologic factors and erythroblast transformation-specific (ETS)-related gene (ERG) expression in prostate cancer patients. Using next-generation sequencing, we identified target genes and regulatory networks.

Methods

ERG expression in 60 radical prostatectomies was compared with pathological findings by association rule mining with the Apriori algorithm. Whole-exome and RNA sequencing were performed on three formalin-fixed, paraffin-embedded ERG-positive and negative prostate cancer samples. A network diagram identifying dominant altered genes was constructed using Cytoscape open-source bioinformatics platform and GeneMania plugin.

Results

Pathologic conditions positive for perineural invasion, apical margins, and Gleason score 3 + 4 = 7 were significantly more likely to be ERG-positive than other pathologic conditions (p = 0.0008), suggesting an association between ERG positivity, perineural invasion, apical margins, and Gleason score 3 + 4 = 7 (Firth’s logistic regression: OR 42.565, 95% CI 1.670–1084.847, p = 0.0232). Results of whole-exome and RNA sequencing identified 97 somatic mutations containing common mutated genes. Regulatory network analysis identified NOTCH1, MEF2C, STAT3, LCK, CACNA2D3, PCSK7, MEF2A, PDZD2, TAB1, and ASGR1 as pivotal genes. NOTCH1 appears to function as a hub, because it had the highest node degree and betweenness. NOTCH1 staining was found 8 of 60 specimens (13%), with a significant association between ERG and NOTCH1 positivity (p = 0.001).

Conclusions

Evaluating the association between ERG expression and pathologic factors, and identifying the regulatory network and pivotal hub may help to understand the clinical significance of ERG-positive prostate cancer.

Artavanis Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284:770–776. https://doi.org/10.1126/science.284.5415.770 CrossRefPubMed

Bethel CR, Faith D, Li X, Guan B, Hicks JL, Lan F, Jenkins RB, Bieberich CJ, De Marzo AM (2006) Decreased NKX3.1 protein expression in focal prostatic atrophy, prostatic intraepithelial neoplasia, and adenocarcinoma: association with gleason score and chromosome 8p deletion. Cancer Res 66:10683–10690. https://doi.org/10.1158/0008-5472.CAN-06-0963 CrossRefPubMed

Brossette SE, Sprague AP, Hardin JM, Waites KB, Jones WT, Moser SA (1998) Association rules and data mining in hospital infection control and public health surveillance. J Am Med Inform Assoc 5:373–381. https://doi.org.ssl.oca.korea.ac.kr/. https://doi.org/10.1136/jamia.1998.0050373

Carvalho FL, Simons BW, Eberhart CG, Berman DM (2014) Notch signaling in prostate cancer: a moving target. Prostate 74:933–945. https://doi.org/10.1002/pros.22811 CrossRefPubMedPubMedCentral

Chaux A, Albadine R, Toubaji A, Hicks J, Meeker A, Platz EA, De Marzo AM, Netto GJ (2011) Immunohistochemistry for ERG expression as a surrogate for TMPRSS2-ERG fusion detection in prostatic adenocarcinomas. Am J Surg Pathol 35:1014–1020. https://doi.org/10.1097/PAS.0b013e31821e8761 CrossRefPubMedPubMedCentral

Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA (2016) The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol 40:244–252. https://doi.org/10.1097/pas.0000000000000530

Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5:R80-R80. https://doi.org/10.1186/gb-2004-5-10-r80 CrossRef

Hedegaard J, Thorsen K, Lund MK, Hein AK, Hamilton Dutoit SJ, Vang S, Nordentoft I, Birkenkamp Demtröder K, Kruhøffer M, Hager H, Knudsen B, Andersen CL, Sørensen KD, Pedersen JS, Ørntoft TF, Dyrskjøt L (2014) Next-generation sequencing of RNA and DNA isolated from paired fresh-frozen and formalin-fixed paraffin-embedded samples of human cancer and normal tissue. PLoS One 9:e98187. https://doi.org/10.1371/journal.pone.0098187 CrossRefPubMedPubMedCentral

Kimura T, Furusato B, Miki J, Yamamoto T, Hayashi N, Takahashi H, Kamata Y, van Leenders GJ, Visakorpi T, Egawa S (2012) Expression of ERG oncoprotein is associated with a less aggressive tumor phenotype in Japanese prostate cancer patients. Pathol Int 62:742–748. https://doi.org/10.1111/pin.12006 CrossRefPubMed

Krstanoski Z, Vokac NK, Zagorac A, Pospihalj B, Munda M, Dzeroski S, Golouh R (2016) TMPRSS2:ERG gene aberrations may provide insight into pT stage in prostate cancer. BMC Urol 16:35. https://doi.org/10.1186/s12894-016-0160-8 CrossRefPubMedPubMedCentral

Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9:357–359. https://doi.org/10.1038/nmeth.1923 CrossRefPubMedPubMedCentral

Lefort K, Ostano P, Mello-Grand M, Calpini V, Scatolini M, Farsetti A, Dotto GP, Chiorino G (2016) Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer. Oncotarget 7:48011–48026. https://doi.org/10.18632/oncotarget.10333 CrossRefPubMedPubMedCentral

Lu LI, Zhang H, Pang J, Hou GL, Lu MH, Gao X (2016) ERG rearrangement as a novel marker for predicting the extra-prostatic extension of clinically localised prostate cancer. Oncol Lett 11:2532–2538. https://doi.org/10.3892/ol.2016.4282 CrossRefPubMedPubMedCentral

Manson Bahr D, Ball R, Gundem G, Sethia K, Mills R, Rochester M, Goody V, Anderson E, O’Meara S, Flather M, Keeling M, Yazbek Hanna M, Hurst R, Curley H, Clark J, Brewer DS, McDermott U, Cooper C (2015) Mutation detection in formalin-fixed prostate cancer biopsies taken at the time of diagnosis using next-generation DNA sequencing. J Clin Pathol 68:212–217. https://doi.org/10.1136/jclinpath-2014-202754 CrossRefPubMed

Mohamed AA, Tan SH, Xavier CP, Katta S, Huang W, Ravindranath L, Jamal M, Li H, Srivastava M, Srivatsan ES, Sreenath TL, McLeod DG, Srinivasan A, Petrovics G, Dobi A, Srivastava S (2017) Synergistic activity with NOTCH inhibition and androgen ablation in ERG-positive prostate cancer cells. Mol Cancer Res 15:1308–1317. https://doi.org/10.1158/1541-7786.mcr-17-0058 CrossRefPubMed

Montojo J, Zuberi K, Rodriguez H, Kazi F, Wright G, Donaldson SL, Morris Q, Bader GD (2010) GeneMANIA Cytoscape plugin: fast gene function predictions on the desktop. Bioinformatics 26:2927–2928. https://doi.org/10.1093/bioinformatics/btq562 CrossRefPubMedPubMedCentral

Neil JR, Schiemann WP (2008) Altered TAB1:I kappaB kinase interaction promotes transforming growth factor beta-mediated nuclear factor-kappaB activation during breast cancer progression. Cancer Res 68:1462–1470. https://doi.org/10.1158/0008-5472.can-07-3094 CrossRefPubMedPubMedCentral

Park K, Tomlins SA, Mudaliar KM, Chiu YL, Esgueva R, Mehra R, Suleman K, Varambally S, Brenner JC, MacDonald T, Srivastava A, Tewari AK, Sathyanarayana U, Nagy D, Pestano G, Kunju LP, Demichelis F, Chinnaiyan AM, Rubin MA (2010) Antibody-based detection of ERG rearrangement-positive prostate cancer. Neoplasia 12:590–598CrossRefPubMedPubMedCentral

Perner S, Mosquera J, Demichelis F, Hofer MD, Paris PL, Simko J, Collins C, Bismar TA, Chinnaiyan AM, De Marzo AM, Rubin MA (2007) TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with invasion. Am J Surg Pathol 31:882–888. https://doi.org/10.1097/01.pas.0000213424.38503.aa CrossRefPubMed

Pettersson A, Graff RE, Bauer SR, Pitt MJ, Lis RT, Stack EC, Martin NE, Kunz L, Penney KL, Ligon AH, Suppan C, Flavin R, Sesso HD, Rider JR, Sweeney C, Stampfer MJ, Fiorentino M, Kantoff PW, Sanda MG, Giovannucci EL, Ding EL, Loda M, Mucci LA (2012) The TMPRSS2:ERG rearrangement, ERG expression, and prostate cancer outcomes: a cohort study and meta-analysis. Cancer Epidemiol Biomarkers Prev 21:1497–1509. https://doi.org/10.1158/1055-9965.EPI-12-0042 CrossRefPubMedPubMedCentral

Scardoni G, Petterlini M, Laudanna C (2009) Analyzing biological network parameters with CentiScaPe. Bioinformatics 25:2857–2859. https://doi.org/10.1093/bioinformatics/btp517 CrossRefPubMedPubMedCentral

Sethi S, Macoska J, Chen W, Sarkar FH (2010) Molecular signature of epithelial-mesenchymal transition (EMT) in human prostate cancer bone metastasis. Am J Transl Res 3:90–99PubMedPubMedCentral

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504. https://doi.org/10.1101/gr.1239303 CrossRefPubMedPubMedCentral

Shin SJ, Park CK, Park SY, Jang WS, Lee JY, Choi YD, Cho NH (2016) Total intraglandular and index tumor volumes predict biochemical recurrence in prostate cancer. Virchows Arch 469:305–312. https://doi.org/10.1007/s00428-016-1971-4 CrossRefPubMed

Smoot ME, Ono K, Ruscheinski J, Wang P, Ideker T (2011) Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27:431–432. https://doi.org/10.1093/bioinformatics/btq675 CrossRefPubMed

Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun X, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310:644–648. https://doi.org/10.1126/science.1117679 CrossRefPubMed

Tomlins SA, Bjartell A, Chinnaiyan AM, Jenster G, Nam RK, Rubin MA, Schalken JA (2009) ETS gene fusions in prostate cancer: from discovery to daily clinical practice. Eur Urol 56:275–286. https://doi.org/10.1016/j.eururo.2009.04.036 CrossRefPubMed

Vargas JE, Porto BN, Puga R, Stein RT, Pitrez PM (2016) Identifying a biomarker network for corticosteroid resistance in asthma from bronchoalveolar lavage samples. Mol Biol Rep 43:697–710. https://doi.org/10.1007/s11033-016-4007-x CrossRefPubMed

Wang X, Leow CC, Zha J, Tang Z, Modrusan Z, Radtke F, Aguet M, de Sauvage FJ, Gao W (2006) Notch signaling is required for normal prostatic epithelial cell proliferation and differentiation. Dev Biol 290:66–80. https://doi.org/10.1016/j.ydbio.2005.11.009 CrossRefPubMed

Wright A, Chen ES, Maloney FL (2010) An automated technique for identifying associations between medications, laboratory results and problems. J Biomed Inform 43:891–901. https://doi.org/10.1016/j.jbi.2010.09.009 CrossRefPubMed

Xu B, Chevarie-Davis M, Chevalier S, Scarlata E, Zeizafoun N, Dragomir A, Tanguay S, Kassouf W, Aprikian A, Brimo F (2014) The prognostic role of ERG immunopositivity in prostatic acinar adenocarcinoma: a study including 454 cases and review of the literature. Hum Pathol 45:488–497. https://doi.org/10.1016/j.humpath.2013.10.012 CrossRefPubMed

Zhu H, Zhou X, Redfield S, Lewin J, Miele L (2013) Elevated Jagged-1 and Notch-1 expression in high grade and metastatic prostate cancers. Am J Transl Res 5:368–378PubMedPubMedCentral

Titel: Association between pathologic factors and ERG expression in prostate cancer: finding pivotal networking
verfasst von: Seung-Ryeol Lee
Young-Deuk Choi
Nam-Hoon Cho
Publikationsdatum: 12.06.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2018
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-018-2685-6

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