Identification and validation of basement membrane‐associated gene AGRN as prognostic and immune‐associated biomarkers in colorectal cancer patients

Abstract

AbstractColorectal cancer (COCA) has a poor prognosis, with growing evidence implicating basement membranes (BMs) in cancer progression. Our goal was to investigate the role and predictive significance of BMs in COCA patients. We obtained BMs‐related genes from cutting‐edge research and used TCGA and GTEx databases for mRNA expression and patient information. Cox regression and LASSO regression were used for prognostic gene selection and risk model construction. We compared prognosis using Kaplan–Meier analysis and examined drug sensitivity differences. The CMAP dataset identified potential small molecule drugs. In vitro tests involved suppressing a crucial gene to observe its impact on tumour metastasis. We developed a 12 BMs‐based approach, finding it to be an independent prognostic factor. Functional analysis showed BMs concentrated in cancer‐associated pathways, correlating with immune cell infiltration and immune checkpoint activation. High‐risk individuals exhibited increased drug sensitivity. AGRN levels were linked to decreased progression‐free survival (p < 0.001). AGRN knockdown suppressed tumour growth and metastasis. Our study offers new perspectives on BMs in COCA, concluding that AGRN is a dependable biomarker for patient survival and prognosis.