Int J Biol Sci 2018; 14(14):2012-2022. doi:10.7150/ijbs.28249
Seven Genes Based Novel Signature Predicts Clinical Outcome and Platinum Sensitivity of High Grade IIIc Serous Ovarian Carcinoma
1. Shanghai Public Health Clinical Center, Department of Medical System Biology, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, P.R.China.
2. Department of Gynecology Oncology, Fudan University Shanghai Cancer Centre, Fudan University, 200032, Shanghai, P.R.China.
3. Department of BioHealth Informatics, School of Informatics and Computing, Indiana University, Indianapolis, IN, US.
*These authors contributed equally to this work.
Background: As a major subtype of ovarian cancer, high grade FIGO stage IIIc serous ovarian carcinoma (HG3cSOC), has various prognosis due to genetic heterogeneity.
Methods: The transcriptome of 401 primary FIGO IIIc serous ovarian samples was screened, seven genes based prognostic model was developed. The prognostic valueof risk score in four different cohorts (TCGA-cohort, Poland-cohort, Japan-cohort and USA-cohort) was validated. The relationship between risk score and other clinical indicators were analyzed. The guide value of risk score for platinum-taxol chemotherapy was also assayed. Tissue microenvironment difference among samples with different risk scores was investigated.
Results: High-risk group (N=200, median survival months: 39.6, 95% CI: 35.9-46.3 months) had a significantly worse prognosis than low-risk group (N=201, median survival months: 52.6, 95% CI: 45.2-64.9 months;). The risk score's performance was validated in Japan-cohort (N=90, Poland-cohort (N=48) and USA-cohort (N=84). The risk score is independent from age, primary tumor size, grade and treatment methods and the performance of risk score is uniform in subgroups. Furthermore, the risk score predicted the response of HG3cSOC to platinum-based regimen after surgery, and this finding was further validated in newly collected China-cohort (N=102). Gene Set Enrichment Analysis (GSEA) and tumor infiltration analysis revealed that risk score reflected the immune infiltration and cell-cell interaction status, and the migration function of candidate genes were also verified.
Conclusions: The optimized seven genes-based model is a valuable and robust model in predicting the survival of HG3cSOC, and served as a valuable marker for the response to platinum-based chemotherapy.
Keywords: High grade FIGO IIIc serous ovarian carcinoma, prognosis, model, transcriptome, chemotherapy, microenvironment.
Liu G, Chen L, Ren H, Liu F, Dong C, Wu A, Liu Z, Zheng Y, Cheng X, Liu L. Seven Genes Based Novel Signature Predicts Clinical Outcome and Platinum Sensitivity of High Grade IIIc Serous Ovarian Carcinoma. Int J Biol Sci 2018; 14(14):2012-2022. doi:10.7150/ijbs.28249. Available from http://www.ijbs.com/v14p2012.htm