Authors: Camila Sinimbú Forte , Amanda Ferreira Vidal , Pablo Diego do Carmo Pinto , Gilderlanio Santana de Araújo

Abstract

Background: The cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is linked to gastrointestinal inflammation and has been implicated in early-onset malignancies. However, its role in gastric cancer remains poorly understood.

Aims: To investigate the CFTR interactome and assess its potential functional involvement across different subtypes of gastric cancer.

Methods: We conducted a system-level in silico analysis using data from the Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD). CFTR expression and co-expression profiles were examined across molecular and histological subtypes of gastric cancer, including signet-ring cell carcinoma (Lauren’s classification). Differential gene expression (DGE) and co-expression analyses were integrated with protein-protein interaction networks, pathway enrichment, and gene ontology (GO) analysis to delineate CFTR’s functional associations.

Results: CFTR did not exhibit significant differential expression across gastric cancer subtypes. However, co-expression analysis identified CFTR as a key hub gene with a distinct interaction network, especially prominent in the signet-ring cell carcinoma subtype. Enrichment analyses revealed that CFTR's interactome is involved in regulatory pathways related to cellular homeostasis, ion transport, and immune modulation, suggesting a noncanonical yet critical role in tumor biology.

Conclusion: While CFTR expression remains stable across gastric cancer subtypes, its interactome reveals significant regulatory roles, particularly in signet-ring cell carcinoma. These findings highlight the potential contribution of CFTR to gastric cancer pathogenesis through its involvement in broader molecular networks rather than through expression changes alone.

Keywords: Gene co-expression network, CFTR, gastric cancer subtypes, signet-ring cell carcinoma