Development and validation of an immune gene-set based Prognostic signature in ovarian cancer

BACKGROUND: Ovarian cancer (OV) is the most lethal gynecological cancer in women. We aim to develop a generalized, individualized immune prognostic signature that can stratify and predict overall survival for ovarian cancer. METHODS: The gene expression profiles of ovarian cancer tumor tissue samples were collected from 17 public cohorts, including 2777 cases totally. Single sample gene set enrichment (ssGSEA) analysis was used for the immune genes from ImmPort database to develop an immune-based prognostic score for OV (IPSOV). The signature was trained and validated in six independent datasets (n = 519, 409, 606, 634, 415, 194). FINDINGS: The IPSOV significantly stratified patients into low- and high-immune risk groups in the training set and in the 5 validation sets (HR range: 1.71 [95%CI: 1.32–2.19; P = 4.04 × 10(−5)] to 2.86 [95%CI: 1.72–4.74; P = 4.89 × 10(−5)]). Further, we compared IPSOV with nine reported ovarian cancer prognostic signatures as well as the clinical characteristics including stage, grade and debulking status. The IPSOV achieved the highest mean C-index (0.625) compared with the other signatures (0.516 to 0.602) and clinical characteristics (0.555 to 0.583). Further, we integrated IPSOV with stage, grade and debulking, which showed improved prognostic accuracy than clinical characteristics only. INTERPRETATION: The proposed clinical-immune signature is a promising biomarker for estimating overall survival in ovarian cancer. Prospective studies are needed to further validate its analytical accuracy and test the clinical utility. FUND: This work was supported by National Key Research and Development Program of China, National Natural Science Foundation of China and Natural Science Foundation of the Jiangsu Higher Education Institutions of China.