Weighted Gene Correlation Network Analysis of Ovarian Cancer Driven by CXCL13- CXCR5 Interactions

Abstract

Abstract Ovarian Cancer (OvCa) is a disease that affects postmenopausal women, with high-grade serous ovarian carcinoma being the most common and lethal type. Many patients are asymptomatic in the early stages of OvCa, thus going undetected, leading to higher patient mortality rates. Identifying biomarkers involved in ovarian cancer progression could enhance current therapeutic outcomes. Our laboratory was the first to show that CXCL13- CXCR5 signaling mediates prostate, breast and lung cancer cell growth, migration, invasion, and survival. We provided evidence that these chemokines are highly elevated in OvCa cell lines and clinical samples. These previous findings provided the rationale to support the hypothesis CXCL13-CXCR5 signaling promotes OvCa progression, metastasis and survival. In this study, we analyzed transcriptome data to determine possible molecular mechanisms and CXCL13-CXCR5 signaling pathways controlling OvCa progression. Weighted Gene Network Co-expression (WGCNA) analysis and Ingenuity Pathway Analysis were used to identify gene coexpression networks correlated with aggressive OvCa clinical phenotypes. CXCR5 was found to be co-expressed with several genes such as RB1, PIK3C3, GNAI1, LTB TNFRSF11B which are known to facilitate OvCa progression and tertiary lymphoid structure formation. Upon further analysis, we found that these gene expressions closely correlated with age at diagnosis and patient relapse. Our study suggests an important role of CXCL13-CXCR5 signaling and reveals an important set of co-expressed epigengenes involved in OvCa relapse.