Bioinformatic profiling identifies a platinum-resistant-related risk signature for ovarian cancer.

Ce WuLinxiu HeQian WeiQian LiLongyang JiangLan ZhaoChunyan WangJianping LiMin-Jie Wei
Published in: Cancer medicine (2019)
Most high-grade serous ovarian cancer (HGSOC) patients develop resistance to platinum-based chemotherapy and recur. Many biomarkers related to the survival and prognosis of drug-resistant patients have been delved by mining databases; however, the prediction effect of single-gene biomarker is not specific and sensitive enough. The present study aimed to develop a novel prognostic gene signature of platinum-based resistance for patients with HGSOC. The gene expression profiles were obtained from Gene Expression Omnibus and The Cancer Genome Atlas database. A total of 269 differentially expressed genes (DEGs) associated with platinum resistance were identified (P < .05, fold change >1.5). Functional analysis revealed that these DEGs were mainly involved in apoptosis process, PI3K-Akt pathway. Furthermore, we established a set of seven-gene signature that was significantly associated with overall survival (OS) in the test series. Compared with the low-risk score group, patients with a high-risk score suffered poorer OS (P < .001). The area under the curve (AUC) was found to be 0.710, which means the risk score had a certain accuracy on predicting OS in HGSOC (AUC > 0.7). Surprisingly, the risk score was identified as an independent prognostic indicator for HGSOC (P < .001). Subgroup analyses suggested that the risk score had a greater prognostic value for patients with grade 3-4, stage III-IV, venous invasion and objective response. In conclusion, we developed a seven-gene signature relating to platinum resistance, which can predict survival for HGSOC and provide novel insights into understanding of platinum resistance mechanisms and identification of HGSOC patients with poor prognosis.