CTGF, FN1, IL-6, THBS1, and WISP1 genes and PI3K-Akt signaling pathway as prognostic and therapeutic targets in gastric cancer identified by gene network modeling

Sep 21, 2026

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Gastric cancer is among the most common malignancies worldwide and remains a leading cause of cancer mortality. This study used gene network modeling to identify critical genes and pathways that could function as biomarkers or therapeutic targets in gastric cancer. Differential expression between gastric cancerous and noncancerous tissues was integrated with Gene Ontology and KEGG pathway enrichment, while hub genes were derived from protein–protein interaction networks (STRING, Cytoscape) and validated using GEPIA2 and DrugBank. CTGF, FN1, IL-6, THBS1, and WISP1 overexpression correlated with reduced overall survival, and PI3K-Akt signaling showed central involvement.

LanguageEnglish

CategoryResearch & Report

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Pages15

Reading Time38 min

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Abstract

Objective

Methods

Differential expression and enrichment analyses

Hub gene identification and validation

Results

Conclusion

Keywords

Introduction

Materials and methods

Analysis CTGF, FN1, IL‑6, THBS1, and WISP1 genes and PI3K‑Akt signaling pathway as prognostic and therapeutic targets in gastric cancer identified by gene network modeling Farzane Khoshdel1 · Negar Mottaghi‑Dastjerdi1 · FatemeYazdani1 · Shirin Salehi1 · Abozar Ghorbani2 · Hamed Montazeri1 · Mohammad Soltany‑Rezaee‑Rad3 · Babak Goodarzy4 Received: 12 December 2023 / Accepted: 7 August 2024 © The Author(s) 2024 OPEN Abstract Objective Gastric cancer (GC) is one of the most common malignancies worldwide and it is considered the fourth most common cause of cancer death. This study aimed to find critical genes/pathways in GC pathogenesis to be used as biomarkers or therapeutic targets. Methods Differentially expressed genes were explored between human gastric cancerous and noncancerous tissues, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analyses were done. Hub genes were identified based on the protein–protein interaction network constructed in the STRING database with Cytoscape software. The hub genes were selected for further investigation using GEPIA2 and DrugBank databases. Results Ten overexpressed hub genes in GC were identified in the current study, including FN1, TP53, IL-6, CXCL5, ELN, ADAMTS2, WISP1, MMP2, CTGF, and THBS1. The study demonstrated the PI3K-Akt pathway’s central involvement in GC, with pronounced alterations in essential components. Survival analysis revealed significant correlations between CTGF, FN1, IL-6, THBS1, and WISP1 overexpression and reduced overall survival times in GC patients. Conclusion A mutual interplay emerged, where PI3K-Akt signaling could upregulate certain genes, forming feedback loops and intensifying cancer phenotypes. The interconnected overexpression of genes and the PI3K-Akt pathway fosters gastric tumorigenesis, suggesting therapeutic potential. DrugBank analysis identified limited FDA-approved drugs, advocating for further exploration while targeting these hub genes could reshape GC treatment. The identified genes could be novel diagnostic/prognostic biomarkers or potential therapeutic targets for GC, but further clinical validation is required. Keywords Biological networks · Biomarker · Differentially expressed genes · Gastric cancer · Therapeutic target 1 Introduction With a poor prognosis, gastric cancer (GC) is the fourth most frequent malignancy worldwide and the fifth most common cause of cancer-related mortality [1]. There have been multiple studies investigating the connection between different risk factors and the development of GC, but the exact molecular network processes are yet to be fully understood [2] . * Negar Mottaghi-Dastjerdi, [Mottaghi.n@iums.ac.ir |](Mottaghi.n@iums.ac.ir |1Department of Pharmacognosy and)[1](Mottaghi.n@iums.ac.ir |1Department of Pharmacognosy and)[Department of Pharmacognosy and](Mottaghi.n@iums.ac.ir |1Department of Pharmacognosy and) Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran. 2Nuclear Agriculture Research School, Nuclear Science and Technology Research Institute (NSTRI), Karaj, Iran. 3Behestan Innovation Factory, Tehran, Iran. 4School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Discover Oncology (2024) 15:344 | [https://doi.org/10.1007/s12672-024-01225-4](https://doi.org/10.1007/s12672-024-01225-4) Understanding the molecular mechanisms involved in the development of GC can help in finding potential targets for early detection and classification, which may improve patient survival rates. Carcinogenesis is a complex process that entails numerous genetic and epigenetic alterations [3]. The most common typeof GC isadenocarcinoma, accounting for about 95% of cases [4]. Numerous studies have been conducted on the epigenetic and genetic changes in various types of GC, with a particular focus on changes in oncogenes, tumor suppressor genes, DNA repair genes, and cell cycle regulators [5].

FAQs

What was the objective of the study on gastric cancer?

The study aimed to identify critical genes and pathways involved in gastric cancer pathogenesis that could serve as biomarkers or therapeutic targets.

How were hub genes and key pathways identified?

Differentially expressed genes were analyzed between gastric cancerous and noncancerous tissues, followed by Gene Ontology and KEGG enrichment. Hub genes were derived from a protein–protein interaction network in STRING using Cytoscape and then selected for further validation with GEPIA2 and DrugBank.

Which genes showed prognostic relevance and what was the key signaling pathway finding?

Overexpression of CTGF, FN1, IL-6, THBS1, and WISP1 was associated with reduced overall survival. The PI3K-Akt pathway showed central involvement, with evidence supporting regulatory interplay that could intensify gastric tumorigenesis.

Sep 21, 2026

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