Development of a Novel Autophagy-related Prognostic Signature for Serous Ovarian Cancer

Abstract

Purpose: Considerable evidence suggests that autophagy plays a crucial role in the biological processes of ovarian cancer. The aim of this study was to develop a novel autophagy-related prognostic signature for serous ovarian cancer.Methods: A univariate Cox proportional regression model was used to analyze mRNA microarray and clinical data in The Cancer Genome Atlas (TCGA) for the purpose of selecting autophagy-related prognostic genes. A multivariate Cox proportional regression model and the survival analysis were used to develop an eight-gene prognostic signature. The multivariate Cox and stratification analysis suggested that this signature was an independent prognostic factor for serous ovarian cancer patients. Bioinformatics functions were investigated by a principal components analysis and gene set enrichment analysis (GSEA). Finally, the correlation between the prognostic signature and gene mutation status was further analyzed in serous ovarian cancer, and especially with regard to the mutation status of BRCA1 and BRCA2 (BRCA1/2) genes.Results: Distinctly different autophagy-related gene expression profiles were identified in normal ovarian tissues and serous ovarian cancer tissues. We profiled an autophagy-related gene set and identified eight genes with significant prognostic values for serous ovarian cancer. Subsequently, an autophagy-related ovarian cancer risk signature was constructed, and patients at a high-risk or low-risk for poor prognosis were identified based on their signature. High-risk patients had significantly shorter overall survival (OS) and disease-free survival (DFS) times than low-risk patients. GSEA results suggested an enhanced intensity of autophagy regulation in high-risk patients when compared with low-risk patients. When studied as an independent prognostic factor for serous ovarian cancer, the significant prognostic value of this signature could be seen in the stratified cohorts. For clinical use, we developed a nomogram that included the prognostic classifier and seven clinical risk factors. Additionally, we identified the 10 most frequently mutated genes found in serous ovarian cancer patients, and analyzed them for their differences in high-risk and low-risk patients. Among 293 patients, 62 had BRCA1/2 gene mutations, and this result was significantly correlated with the autophagy-related prognostic signature.Conclusions: Our findings suggest that the eight-gene autophagy-related signature could serve as an independent prognostic indicator for cases of serous ovarian cancer.

Prognostic value of an autophagy-related gene expression signature for endometrial cancer patients

“…Several autophagy-related prognostic indicators had already been proposed. For example, An Y, et al developed an eight-gene autophagy-related signature, which could serve as an independent prognostic indicator for serous ovarian cancer [21]. Wang SS, et al identi ed three prognostic ARGs (JUN, MYC, and ITGA3) and validated a clinical autophagy-based index in predicting overall survival of bladder cancer [22].…”

Identification and Validation of an Individualized Autophagy-Clinical Prognostic Index in Gastric Cancer Patients

“…Gene signature is often applied to forcast the prognosis of a variety of tumors in the past few years [22], which is even better than TNM staging and histopathological diagnosis in some extent [23]. Gene signatures based on ATGs have been reported in a variety of cancers, such as serous ovarian cancer, breast cancer, colon cancer and glioma [24][25][26][27]. For example, Liu and colleagues recently reported a 14 autophagy related signature based on relapse free survival in patients with non-small cell lung cancer [28].…”

Identification and Validation of an Individualized Autophagy-Clinical Prognostic Index in Gastric Cancer Patients

“…Gene signature is often applied to forcast the prognosis of a variety of tumors in the past few years [22], which is even better than TNM staging and histopathological diagnosis in some extent [23]. Gene signatures based on ATGs have been reported in a variety of cancers, such as serous ovarian cancer, breast cancer, colon cancer and glioma [24][25][26][27]. There is also a lot of evidence implying the interaction between autophagy and apoptosis [31].…”