Identification of cancer-associated fibrolast subtypes and distinctive role of MFAP5 in CT-detected extramural venous invasion in gastric cancer

作者：Bo Gao, Xinyi Gou, Caizhen Feng, Yinli Zhang, Huining Gu, Fan Chai, Yi Wang, Yingjiang Ye, Nan Hong, Guo‐Hua Hu, Boshi Sun, Jin Cheng, Hao Yang · 发表于：Translational Oncology · 年份：2024 · DOI：10.1016/j.tranon.2024.102188 · 被引用次数：7 · 研究领域：Gastric Cancer Management and Outcomes、Cancer-related gene regulation、Cancer-related molecular mechanisms research

• Radiogenomics and single-cell sequencing analyses revealed that the degree of CAFs infiltration was directly proportional to the EMVI score in GC patients. • MFAP5+CAFs subtypes were negatively correlated with GC patient prognosis and were enriched in tumor lactylation modification and EMT pathways. • Molecular biology experiments and cells co-culture in vitro revealed MFAP5+ CAFs promote EMT of GC cell line via lactylation modification. • We successfully established an orthotopic GC nude mouse model with EMVI imaging characteristics. • CAFs of up-regulated MFAP5 can promote the formation of EMVI imaging in the animal model. Extramural venous invasion (EMVI) detected by computed tomography has been identified as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). Cancer-associated fibroblasts (CAFs) are critical for remodeling the tumor microenvironment in GCs. Here, we report that MFAP5+ CAFs promote the formation of EMVI imaging in GC. We detected gene expression in pathological samples from 13 advanced GC patients with EMVI. Radiogenomics results showed the degree of CAFs infiltration was directly proportional to the EMVI score and EMT pathway in GC patients. Single-cell sequencing data analysis results showed that MFAP5+CAFs subtypes in GC were negatively correlated with patient prognosis and were enriched in tumor lactylation modification and EMT pathways. Immunohistochemistry results showed that the expression of MFAP5, L-l...