Identification of Hub Genes in High-Grade Serous Ovarian Cancer Using Weighted Gene Co-Expression Network Analysis

Abstract

Background: High-grade serous ovarian cancer (HGSOC) is the most malignant gynecologic tumor. This study reveals biomarkers related to HGSOC incidence and progression using the bioinformatics method. Material/Methods: Five gene expression profiles were downloaded from GEO. Differentially-expressed genes (DEGs) in HGSOC and normal ovarian tissue samples were screened using limma and the function of DEGs was annotated by KEGG and GO analysis using clusterProfiler. A co-expression network utilizing the WGCNA package was established to define several hub genes from the key module. Furthermore, survival analysis was performed, followed by expression validation with datasets from TCGA and GTEx. Finally, we used single-gene GSEA to detect the function of prognostic hub genes. Results: Out of the 1874 DEGs detected from 114 HGSOC versus 49 normal tissue samples, 956 were upregulated and 919 were downregulated. The functional annotation indicated that upregulated DEGs were mostly enriched in cell cycle, whereas the downregulated DEGs were enriched in the MAPK or Ras signaling pathway. Two modules significantly associated with HGSOC were excavated through WGCNA. After survival analysis and expression validation of hub genes, we found that 2 upregulated genes (MAD2L1 and PKD2) and 3 downregulated genes (DOCK5, FANCD2 and TBRG1) were positively correlated with HGSOC prognosis. GSEA for single-hub genes revealed that MAD2L1 and PKD2 were associated with proliferation, while DOCK5, FANCD2, and TBRG1 were associated with immune response. Conclusions: We found that FANCD2, PKD2, TBRG1, and DOCK5 had prognostic value and could be used as potential biomarkers for HGSOC treatment.

An Overview of Candidate Therapeutic Target Genes in Ovarian Cancer

“…A higher somatic mutation burden has been recently reported in OC for the POLE gene, encoding for an enzyme involved in the DNA repair and replication; the impact of POLE mutations also seems to be more prominent in sporadic OC than in familiar one [ 115 ]. Upregulation of the RPA3 gene has been associated with HGSOC proliferation [ 116 ].…”

PRSS1 Upregulation Predicts Platinum Resistance in Ovarian Cancer Patients

“…Among all negatively correlated co-expression genes, ANHAK (6th) (Chatterjee et al, 2006 ) (Sheets et al, 2016 ) and DOCK5 (7th) exhibited correlations with ovarian cancer ( Supplementary Table 3 ; Figure 4D ). Wu et al pointed out that DOCK5 is down-regulated in ovarian cancer tissues and related to immune response (Wu et al, 2020 ).…”

Synergistic AHR Binding Pathway with EMT Effects on Serous Ovarian Tumors Recognized by Multidisciplinary Integrated Analysis

“…In our experiments, we also identified 13 highly relevant DEGs. Many related studies have examined how these DEGs affected the formation of serous ovarian tumors, such as tyrosine kinase related DEGs ( PTK2B , KIT , and SRC ) [ 74 , 75 , 76 ], crucial factors known to be related to tumorigenesis ( AKT1 , MTOR , MAPK3 ) [ 64 , 77 , 78 , 79 , 80 ], DEGs related to cellular metabolism and immunity ( EDN1 , IL1B , INS , APP , LEP ) [ 29 , 56 , 60 , 81 , 82 , 83 , 84 , 85 , 86 ], and agents for signal transmission and channels of cell membranes ( CDK5 and ATP1B1 ) [ 59 , 87 , 88 ]. Among these DEGs, we found that SRC has consistently poor effects on the survival of serous ovarian carcinoma patients with a poor prognosis of PFS and OS.…”