Identification of GREM-1 and GAS6 as specific biomarkers for cancer-associated fibroblasts derived from patients with non-small cell lung cancer

Cancer-associated fibroblasts (CAFs) play a pivotal role in the tumor microenvironment. We conducted an analysis using RNA sequencing to identify specific markers for CAFs compared to normal fibroblasts (NFs) in non-small cell carcinoma (NSCLC) under various condition. We analyzed 22 CAF samples and 11 NF samples. The 22 CAF samples consisted of 12 adenocarcinomas and 10 squamous cell carcinomas (SqCC), with 16 samples from the lungs and 6 samples from the lymph nodes. Notably, COL11A1, GREM1, CD36, and GAS6 showed higher expression in CAFs than in NFs, whereas TNC and CXCL2 were more highly expressed in NFs. CD36 levels were elevated in CAFs from lymph nodes (LN-CAFs) compared with those from lung specimens (Lung-CAFs) and NFs. COL11A1 levels in Lung-CAFs surpassed those in LN-CAFs and NFs. Both GREM1 and GAS6 showed strong expression in Lung-CAFs and LN-CAFs relative to NFs. CAFs exhibited features of the myofibroblast CAF subpopulation, whereas NFs displayed traits of the antigen-presenting CAF subtype. In NSCLC, GREM1 and GAS6 can be valuable diagnostic and therapeutic targets for CAFs from primary tumors and metastatic sites; they warrant further study.