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

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: We established a novel scoring system based on pivotal ATG genes, which accurately predicts the outcomes of patients with advanced ovarian cancer after chemotherapy. IMPACT: The present ATG scoring system may provide a novel perspective and a promising tool for the development of personalized therapy in the future. ©2019 American Association for Cancer Research.