Identification of Critical Genes Associated with Intrahepatic Cholangiocarcinoma: Weighted Gene Co-expression Network Analysis

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a liver cancer originating in the bile duct and is characterized by its complex nature and poor prognosis. While immunotherapy holds promise for modulating the tumour microenvironment and impeding cancer growth, its role in ICC remains largely unexplored. This study aims to identify critical immune-related genes that may influence the progression of ICC. We employed an in silico approach to analyze gene expression data from human ICC samples, sourced from the Gene Expression Omnibus database. We performed differential gene expression analysis in conjunction with weighted gene co-expression network analysis (WGCNA) to investigate the relationships between differentially expressed genes (DEGs) and 22 immune cell types, which were estimated using the CIBERSORT algorithm. Hub gene identification and pathway enrichment analysis were performed to pinpoint potential regulatory genes and their associated molecular pathways. Nine hub genes, namely AGXT, MBL2, SERPINC1, RHOA, TTR, SLC2A2, PLG, C8A, and SOX9, were found to be positively associated with CD4 naïve T cells, with pathways linked to cancer progression and poor prognosis. This study leverages an in silico systems network biology approach to uncover critical genes associated with ICC. Such findings may aid in the development of multimodal and multiagent immunotherapeutic approaches for disease treatment.

Received: 1 August 2024 | Revised: 13 December 2024 | Accepted: 17 February 2025

Conflicts of Interest

The authors declare that they have no conflicts of interest to this work.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Author Contribution Statement

Tammanna R. Sahrawat: Conceptualization, Methodology, Validation, Investigation, Resources, Data curation, Writing – original draft, Writing – review & editing, Supervision, Project administration. Aayushi Notra: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Resources, Data curation, Writing – original draft, Writing – review & editing, Visualization, Project administration.