Evaluating the Potential of COL8A1 as a Therapeutic Target for Chemoresistance, Disease Progression, and a Prognostic Marker in Gastric Cancer

Abstract

This study aimed to identify key genes associated with post-chemotherapy recurrence in gastric cancer patients. Gene expression data from multiple cohorts were analysed to determine differentially expressed genes between recurrent and non-recurrent cases. A prognostic risk model incorporating COL8A1, HSPB7 and SLIT2 was developed and validated across six independent cohorts. The risk score demonstrated significant associations with disease-free and overall survival, tumour grade and molecular subtypes. Notably, the risk score showed potential as a predictor of immunotherapy response, outperforming established markers such as microsatellite instability score and Epstein-Barr virus status. Analysis of the tumour immune microenvironment revealed a correlation between risk score and M2 macrophage infiltration. A nomogram integrating the risk score with clinical factors demonstrated high accuracy in predicting patient survival. Further investigation of COL8A1 revealed its significant role in gastric cancer cell proliferation, metastasis, and chemoresistance. In vitro and in vivo experiments showed that COL8A1 knockdown inhibited cancer cell growth, invasion, and metastasis while enhancing chemosensitivity. These findings provide valuable insights into the molecular mechanisms of gastric cancer recurrence and offer potential biomarkers for prognosis and treatment response prediction. The study highlights the importance of integrating genomic data with clinical information to improve patient stratification and personalised treatment strategies in gastric cancer management.

Keywords: COL8A1; chemotherapy; gastric cancer; immunotherapy; recurrence.