A Novel Scoring System for Pivotal Autophagy-Related Genes Predicts Outcomes after Chemotherapy in Advanced Ovarian Cancer Patients.

Abstract

In the clinical practice of ovarian cancer, the application of autophagy, an important regulator of carcinogenesis and chemoresistance, is still limited. This study aimed to establish a scoring system based on expression profiles of pivotal autophagy-related (ATG) genes in patients with stage III/IV ovarian cancer who received chemotherapy. Data of ovarian serous cystadenocarcinoma in The Cancer Genome Atlas (TCGA-OV) were used as training dataset. Two validation datasets comprised patients in a Chinese local database and a dataset from the Gene Expression Omnibus (GEO). ATG genes significantly (P < 0.1) associated with overall survival (OS) were selected and aggregated into an ATG scoring scale, of which the abilities to predict OS and recurrence-free survival (RFS) were examined. Forty-three ATG genes were selected to develop the ATG score. In TCGA-OV, patients with lower ATG scores had better OS [HR = 0.41; 95% confidence interval (CI), 0.26-0.65; P < 0.001] and RFS [HR = 0.47; 95% CI, 0.27-0.82; P = 0.007]. After complete or partial remission to primary therapy, the rate of recurrence was 47.2% in the low-score group and 68.3% in the high-score group (odds ratio = 0.42; 95% CI, 0.18-0.92; P = 0.03). Such findings were verified in the two validation datasets. We established a novel scoring system based on pivotal ATG genes, which accurately predicts the outcomes of patients with advanced ovarian cancer after chemotherapy. The present ATG scoring system may provide a novel perspective and a promising tool for the development of personalized therapy in the future.