Development and validation of an immune-related prognostic signature for ovarian cancer based on weighted gene co-expression network analysis
Abstract Background Ovarian cancer is one of the most lethal diseases of women. The prognosis of ovarian cancer patients was closely correlated with immune cell expression and immune responses. Therefore, it is important to identify a robust prognostic signature, which not only correlates with prognoses but also with immune responses in ovarian cancer, thus, providing immune-related patient therapies. Methods Weighted gene co-expression network analysis (WGCNA) was used to identify candidate genes correlated with ovarian cancer prognoses. Univariate and multivariate cox regression analyses were used to construct the prognostic signature. The Kaplan-Meier method was used to predict survival, and the immune-related bioinformatics analysis was performed using R software. The relationship between the signature and clinical parameters was analyzed with GraphPad Prism 7 and SPSS software. Results Gene expression from The Cancer Genome Atlas dataset was used to perform the WGCNA analysis, and identified candidate prognostic-related genes in patients with ovarian cancer. According to the Cox regression analysis, the prognostic signature was constructed, which divided patients into two groups. The high-risk group showed the least favorable prognosis. Three independent cohorts from the Gene Expression Omnibus (GEO) database were used for the validation studies. According to the immune analyses, the GEO database signatures were significantly correlated with the immune statuses of ovarian cancer patients. By analyzing the combination of the prognostic signature and total mutational burden (TMB), ovarian cancer patients were divided into four groups. In these groups, memory B cell, resting memory CD4 T cell, M2 macrophage, resting mast cell and neutrophil were found significant distinctions among these groups. Conclusions This novel signature predicted the prognosis of ovarian cancer patients precisely and independently and showed significant correlations with immune responses. Therefore, this prognostic signature might could indicate targeted immunotherapies for ovarian cancer patients.