Background
Methods
Search strategy
Inclusion criteria
Exclusion criteria
Data extraction
Statistical analysis
Results
Description of selected studies
Study | Year | Country | Cancer type | Case (n) | Age (Median/Mean, years) | Tumor stage (I/II/III/IV) | Follow-up (Median/Mean, months) | Study type | Method | Cut off value | Endpoints | NOS |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Gerald. et al | 2006 | Austria | Colorectal cancer | 143 | NA | 29/24/78/12 | 51.8a | Retrospective | IHC | High expression: score (5–12) Low expression: score (0–4) | OS | 8 |
K. et al | 2006 | Japan | Endometrial cancer | 80 | 57.2a | 54/10/10/6 | 71.6b | Retrospective | IHC | High expression: score (4–6) Low expression: score (0–3) | OS, PFS | 8 |
Rainer. et al | 2007 | Japan | Renal cell carcinoma | 55 | NA | 22/33 | NA | Retrospective | qPCR | High expression: Above the 80th percentile | OS | 6 |
Ke. et al | 2008 | China | Hepatocellular carcinoma | 138 | NA | NA | NA | Retrospective | IHC | High expression: score (5–9) Low expression: score (0–4) | OS | 8 |
Kazuhiko. et al | 2008 | Japan | Endometrial Cancer | 65 | 57.7a | 44/6/9/6 | 72b | Retrospective | IHC | High expression: score (4–5) Low expression: score (0–3) | OS, PFS | 8 |
Hiroshi. et al | 2009 | Japan | Osteosarcoma | 47 | 15b | 0/47/0/0 | 67.4b | Retrospective | IHC | High expression: score (4) Low expression: score (0–3) | OS | 7 |
Tomoko. et al | 2010 | Japan | Cervical cancer | 112 | NA | 67/45/0/0 | NA | Retrospective | IHC | High expression: > 50% of tumor cells were stained | OS, PFS | 7 |
Jacek. et al | 2011 | Poland | Vulvar squamous cell carcinoma | 76 | 69.5b | NA | 51.23b | Retrospective | IHC | > 50% of tumor cells were stained with clusters of higher intensity of expression | OS | 8 |
Reinhart. et al | 2011 | Belgium | Melanoma | 116 | 52b | NA | 71b | Prospective | IHC | Almost none/weak versus strong IDO expression | OS, PFS | 9 |
Renske. et al | 2012 | Netherland | Endometrial carcinoma | 355 | 64b | 196/58/77/44 | 63.6b | Prospective | IHC | High expression: score (4–6) Low expression: score (0–3) | DFS | 8 |
Jin. et al | 2013 | China | Laryngeal squamous cell carcinoma | 187 | 52.4b | 20/58/88/21 | 48.56a | Retrospective | IHC | High expression: score (3–4) Low expression: score (0–2) | OS, DFS | 9 |
Yunlong. et al | 2015 | China | Esophageal squamous cell cancer | 196 | 54b | 113(I–II)/83(III–IV) | NA | Prospective | IHC | High expression: score (5–12) Low expression: score (0–4) | OS | 8 |
Maciej. et al | 2015 | Poland | Melanoma | 48 | 56.9b | NA | 30.3b | Retrospective | IHC | High expression: score > 47.39 Low expression: score ≤ 47.39 | OS | 6 |
Ahlem. et al | 2016 | Tunisia | Nasopharyngeal carcinoma | 71 | NA | 10(I–II)/53(III–IV) | 30b | Prospective | IHC | High expression: score (4–5) Low expression: score (0–3) | OS, PFS | 7 |
Hao. et al | 2016 | China | Gastric adenocarcinoma | 357 | 60.3a | 80/79/198/0 | 41b | Retrospective | IHC | With the X-tile software, the cut-off point was 282, 51% patients were separated into the IDO high expression subgroup | OS | 7 |
Tao. et al | 2017 | China | Pancreatic cancer | 80 | NA | 10(I–II)/53(III–IV) | 40b | Prospective | IHC | High expression: score (> 4) Low expression: score (≤4) | OS | 8 |
Tvrtko. et al | 2017 | Croatia | Bladder carcinomas | 74 | 65.3a | NA | NA | Prospective | qPCR | IDO-positive group, in which expression of IDO gene was detected, regardless of the level of expression. | OS | 7 |
Daniel. et al | 2017 | USA | Breast cancer | 362 | NA | 278(I–II)/63(III–IV) | NA | Retrospective | IHC | Median cut-point was used to stratify IDO1 scores in low and high statuses. | OS | 8 |
Lijie. et al | 2017 | USA | Glioblastoma | 148 | NA | NA | NA | Prospective | qPCR | IDO1 mRNA levels were stratified into IDO1- low and -high expressing groups based on the determined cutoff values. | OS | 8 |
Wenjuan. et al | 2018 | China | Colorectal cancer | 95 | NA | NA | NA | Retrospective | IHC | High expression: score (2–3) Low expression: score (0–1) | OS | 7 |
Yufeng. et al | 2018 | Taiwan (China) | Thymic carcinoma | 69 | 54a | 1/3/45/20 | 46b | Retrospective | IHC | High expression: score (2–3) Low expression: score (0–1) | OS, PFS | 8 |
Hiroto. et al | 2018 | Japan | Esophageal cancer | 182 | 66.5a | 69/63/41/9 | NA | Retrospective | IHC | High expression: score (2–3) Low expression: score (0–1) | RFS | 7 |
Yuki. et al | 2018 | Japan | Esophageal Cancer | 305 | 66a | 123/80/102/0 | 44.4b | Prospective | IHC | (0; no expression, 1; weak expression, 2; moderate expression or 3; strong expression) | OS | 9 |
Masaaki. et al | 2018 | Japan | Gastric Cancer | 60 | 67.8a | 0/0/60/0 | 41a | Retrospective | IHC | A total score of greater than 4+ was defined as IDO positive expression | OS, DFS | 8 |
Tamkin. et al | 2019 | Australia | Malignant pleural mesothelioma | 67 | 65b | NA | NA | Retrospective | IHC | Negative Positive (> 0%) | OS | 7 |
Wenjuan. et al | 2019 | China | Adenosquamous Lung Carcinoma | 183 | 58b | 52/41/71/19 | NA | Retrospective | IHC | High- and low-expression based on the determined cutoff values. | OS | 8 |
Devarati. et al | 2019 | USA | Anal cancer | 63 | 61b | 7/24/9/21 (2 unknown) | 35b | Retrospective | IHC | Positive (> 50% IDO1 expression) | OS | 8 |
Julia. et al | 2019 | Germany | Rectal cancer | 91 | 64b | NA | NA | Retrospective | IHC | High expression: score (3–6) Low expression: score (0–2) | OS, DFS | 8 |
Nadia. et al | 2019 | Tunisia | Vulvar squamous cell carcinoma | 61 | 65.61a | 29/4/26/2 | NA | Retrospective | IHC | High expression: score (3) Low expression: score (0–2) | OS, DFS | 7 |
Sha. et al | 2019 | China | Esophageal squamous cell carcinoma | 158 | 56b | 0/34/124/0 | 40.2b | Retrospective | IHC | Positive (> 50% IDO1 expression) | RFS | 8 |
Yuhshyan. et al | 2019 | Taiwan (China) | Bladder cancer | 108 | 68a | 45/43/19/1 | 45b | Retrospective | IHC | Strongly Positive (> 25% IDO1 expression) | OS, PFS | 8 |
Impact of IDO expression on cancer prognosis
Subgroup analysis
Stratified analysis | Effect size | NO. of study | Cases | HR | Heterogeneity | ||
---|---|---|---|---|---|---|---|
Pooled HR (95% CI) | P value | I2 (%) | p value | ||||
All studies | |||||||
OS | OS | 28 | 3457 | 1.92 (1.52–2.43) | < 0.001 | 81.1 | < 0.001 |
TTP | TTP | 14 | 1815 | 2.25 (1.58–3.22) | < 0.001 | 54.8 | 0.007 |
Study location | |||||||
Asia | OS | 16 | 2137 | 2.12 (1.54–2.92) | < 0.001 | 68.5 | < 0.001 |
TTP | 9 | 1121 | 2.48 (1.74–3.55) | < 0.001 | 11.4 | 0.342 | |
Other countries | OS | 12 | 1320 | 1.66 (1.17–2.37) | 0.005 | 82.2 | < 0.001 |
TTP | 5 | 694 | 1.99 (1.32–2.98) | 0.001 | 14.3 | 0.323 | |
Detection method | |||||||
IHC | OS | 25 | 3180 | 1.86 (1.46–2.38) | < 0.001 | 81.3 | < 0.001 |
TTP | 14 | 1815 | 2.25 (1.58–3.22) | < 0.001 | 54.8 | 0.007 | |
qPCR | OS | 3 | 277 | 2.11 (1.42–3.13) | < 0.001 | 17.7 | 0.297 |
Sample size | |||||||
< 70 | OS | 9 | 535 | 2.25 (1.31–3.88) | 0.003 | 75.5 | < 0.001 |
TTP | 4 | 255 | 2.49 (1.51–4.10) | < 0.001 | 0.0 | 0.72 | |
70–120 | OS | 10 | 903 | 2.37 (1.42–3.95) | 0.001 | 55.9 | 0.02 |
TTP | 6 | 578 | 2.43 (1.09–5.44) | 0.03 | 72.8 | 0.003 | |
> 140 | OS | 9 | 2019 | 1.60 (1.18–2.18) | 0.003 | 75.8 | < 0.001 |
TTP | 4 | 882 | 1.98 (1.12–3.51) | 0.019 | 63.2 | 0.043 | |
Study type | |||||||
Retrospective | OS | 21 | 2807 | 1.82 (1.39–2.40) | < 0.001 | 81.5 | < 0.001 |
TTP | 11 | 1273 | 2.32 (1.50–3.60) | < 0.001 | 57.9 | 0.008 | |
Prospective | OS | 7 | 650 | 1.98 (1.57–2.49) | < 0.001 | 0 | 0.6 |
TTP | 3 | 542 | 2.09 (1.03–4.23) | 0.04 | 56.2 | 0.102 | |
Cancer type | |||||||
Digestive system tumor | OS | 10 | 1528 | 1.79 (1.38–2.31) | < 0.001 | 40.8 | 0.085 |
Reproductive system tumor | OS | 6 | 756 | 2.39 (1.53–3.72) | < 0.001 | 34.9 | 0.175 |
Bladder cancer | OS | 2 | 182 | 2.90 (1.32–6.15) | 0.006 | 0.0 | 0.521 |
Colorectal cancer | OS | 2 | 238 | 2.32 (1.22–4.42) | 0.01 | 0.0 | 0.655 |
Endometrial cancer | OS | 2 | 145 | 6.64 (1.41–31.27) | 0.017 | 0.0 | 0.99 |
Esophageal cancer | OS | 2 | 501 | 1.76 (1.28–2.43) | 0.001 | 0.0 | 0.79 |
Esophageal cancer | TTP | 2 | 340 | 2.23 (0.91–5.49) | 0.081 | 77.9 | 0.033 |
Gastric Cancer | OS | 2 | 417 | 1.68 (1.22–2.32) | 0.001 | 1.5 | 0.314 |
Melanoma | OS | 2 | 164 | 1.95 (0.45–8.49) | 0.376 | 84.8 | 0.01 |
Vulvar squamous cell carcinoma | OS | 2 | 137 | 2.92 (1.69–5.04) | < 0.001 | 0.0 | 0.69 |
Age (Mean/Median) | |||||||
< 60 years | OS | 9 | 991 | 2.02 (1.22–3.36) | 0.007 | 83.6 | < 0.001 |
> 60 years | OS | 10 | 1262 | 1.76 (1.16–2.67) | 0.008 | 68.8 | 0.001 |
Follow-up (Median/Mean) | |||||||
≤ 45 months | OS | 8 | 1092 | 1.90 (1.29–2.78) | 0.001 | 79.4 | < 0.001 |
> 45 months | OS | 8 | 783 | 3.41 (2.41–4.83) | < 0.001 | 0.0 | 0.97 |
Study quality | |||||||
NOS score > 7 | OS | 18 | 2825 | 2.00 (1.48–2.69) | < 0.001 | 72.6 | < 0.001 |
NOS score ≤ 7 | OS | 10 | 632 | 1.75 (1.20–1.57) | < 0.001 | 72.4 | < 0.001 |