VGLL3 expression is associated with macrophage infiltration and predicts poor prognosis in epithelial ovarian cancer

Abstract

Background High-grade serous ovarian carcinoma (HGSOC) is the most common histologic type of epithelial ovarian cancer (EOC). Due to its poor survival outcomes, it is essential to identify novel biomarkers and therapeutic targets. The hippo pathway is crucial in various cancers, including gynaecological cancers. Herein, we examined the clinicopathological significance of the key genes of the hippo pathway in HGSOC. Method The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data were curated to analyse the mRNA expression as well as the clinic-pathological association and correlation with immune cell infiltration in HGSOC. The protein levels of significant genes in the HGSOC tissue were analysed using Tissue Microarray (TMA)-based immunohistochemistry. An overall survival analysis was conducted using the log-rank test method and cox regression analysis. Finally, DEGs pathway analysis was performed to identify find the signalling pathways associated with VGLL3. Result VGLL3 mRNA expression was significantly correlated with both advanced tumour stage and poor overall survival (OS) (p = 0.046 and p = 0.003, respectively). The result of IHC analysis also supported the association of high VGLL3 protein with poor OS in HGSOC. Further, VGLL3 expression was significantly associated with tumour infiltrating macrophages. VGLL3 expression and macrophages infiltration were both found to be independent prognostic factors (p = 0.003 and p = 0.024, respectively) for HGSOC. VGLL3 was associated with 3,981 gene expressions (p < 2.04e−4), and with four known and three novel cancer-related signalling pathways, thus implying that VGLL3 is involved in the deregulation of many genes and pathways. Conclusion Our study revealed that VGLL3 may play a distinct role in clinical outcomes and immune cell infiltration in patients with HGSOC and that it may be a potential prognostic marker of EOC.