COL4A1 Promotes Gastric Cancer Progression by Regulating Tumor Invasion, Tumor Microenvironment and Drug Sensitivity.

[BACKGROUND] Collagen type IV alpha 1 chain (COL4A1), which has been proven to be a potential biomarker in Gastric Cancer (GC), but its role in tumors and the tumor microenvironment (TME) needs further explanation.

[METHODS] We analysed the relationship between COL4A1 and clinical characteristics based on The Cancer Genome Atlas (TCGA) database and verified by tissue microarrays as well as GC cell lines using immunohistochemistry, Q-PCR, western blot, cell proliferation assays, colony formation assays, cell invasion and migration assays. The immune infiltration and drug sensitivity information between high and low COL4A1 expression were analysed by R package and pRRophetic package. Finally, we established a nomogram based on COL4A1 expression using the bootstrap method.

[RESULTS] COL4A1 was overexpressed in gastric carcinoma compared with normal gastric tissue, indicating a poor prognosis of GC patients in the TCGA database which were also validated by GC tissue microarrays. GO, KEGG and hallmark enrichment analyses indicated that COL4A1 was mainly associated with the extracellular matrix than malignant proliferation. By siRNA transfection, we found that COL4A1 knockdown inhibited cell colony formation, invasion and migration but did not affect cell proliferation, similar to previous results. Immune infiltration and drug sensitivity analysis showed that COL4A1 was negatively correlated with antitumor immunity and positively correlated with multidrug resistance. By developing a nomogram model based on 8 risk factors, including COL4A1, patients with better clinical outcomes could be accurately distinguished.

[CONCLUSION] This study established COL4A1 as a prognostic marker and a potential therapeutic target in gastric cancer. Our findings demonstrate that COL4A1 enhances tumor progression and multidrug resistance while inhibiting antitumor immunity. These results underscore the significance of COL4A1 in gastric cancer and suggest its potential for developing targeted therapies.