open access: JCI - Prognostically relevant gene signatures of high-grade serous ovarian carcinoma

 Blogger's Note: technical

JCI - Prognostically relevant gene signatures of high-grade serous ovarian carcinoma
  
Introduction

High-grade serous ovarian carcinoma (HGS-OvCa) accounts for 60%–80% of the approximately 26,000 women diagnosed with epithelial ovarian carcinoma in the US annually (1, 2). Known risk determinants for the development of ovarian carcinoma include BRCA1/BRCA2 mutations, family history, nulliparity, oral contraceptive use, tubal ligation, pregnancy, and lactation (1, 3). A common treatment regimen consists of tumor debulking, followed by administration of platinum and taxane-based chemotherapy (4). The advanced stage at which most patients present, combined with the high rate of relapse, results in a 5-year survival rate less than 40% (5, 6). Identification of nonresponders and patients with primary platinum resistance (recurrence less than 6 months after last chemotherapy cycle) is an important step toward achieving greater life expectancy for serous ovarian carcinoma patients (7). Gene expression profiles have been established that are associated with overall survival (8, 9), debulking status (10), and response to platinum therapy (11–15). Despite those encouraging developments, no biomarkers for prediction of response to therapy are yet in clinical use.
Gene expression–based outcome predictors have had the greatest impact in breast cancer, where gene signature–based assays of recurrence, chemotherapy efficacy, and metastasis were developed with the potential to guide therapy decisions (16–18). Predictors of prognosis have been developed for other cancers, but have not necessarily led to changes in clinical practice. In addition to predicting survival, the potential of prognostic classifiers lies in the ability to recognize categories of patients that are more likely to respond to particular therapies. For example, the Mesenchymal expression subtype of glioblastoma is being investigated in relation to response to angiogenesis inhibitors such as bevacizumab (19)......