Abstract 1354: Identification of <i>GREM-1</i> and <i>GAS6</i> as specific biomarkers for cancer-associated fibroblasts derived from patients with non-small cell lung cancer

Abstract Background/Aims: Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor stroma. They are primarily associated with tumor maintenance and promotion via diverse mechanisms in cancer. Using RNA sequencing, we conducted an analysis aimed at distinguishing distinct markers indicative of CAFs compared to normal fibroblasts (NFs) within the context of non-small cell lung cancer (NSCLC) across diverse conditions. Methods: We conducted RNA sequencing analysis on 22 CAFs and 11 NFs from patients with NSCLC. CAFs and NFs were isolated and cultured from tumor tissues (primary tumor or metastatic lymph nodes) and from the most distant non-tumor tissues of the resected lungs, respectively, in NSCLC patients. We performed bulk-RNA sequencing analysis using total RNA from cultured cell pellets of CAFs or NFs. Differential expression, gene set enrichment and CAF subpopulation prediction analyses were performed. Results: 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. Conclusions: In NSCLC, GREM1 and GAS6 can be valuable diagnostic and therapeutic targets for CAFs from primary tumors and metastatic sites; they warrant further study. Citation Format: Bo-Guen Kim, Kyunghee Park, Mina Hwang, Hyewon Lee, Kyung-Mi Park, Junsu Choe, Sun Hye Shin, Byeong-Ho Jeong, Kyungjong Lee, Jung Hee Lee, Yeong Jeong Jeon, Jong Ho Cho, Hong Kwan Kim, Woong-Yang Park, Sang-Won Um. Identification of GREM-1 and GAS6 as specific biomarkers for cancer-associated fibroblasts derived from patients with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1354.