Cancer-Associated Fibroblasts Genes and Transforming Growth Factor Beta Pathway in Gastric Cancer for Novel Therapeutic Strategy

Background-Objective: Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment of gastric cancer (GC). Understanding the molecular characteristics of CAFs-associated genes (CAFGs) is essential for elucidating their role in tumor progression and prognosis. This review aims to summarize the current knowledge on CAFGs, highlighting their expression patterns, prognostic significance, and potential functional mechanisms. Methods: A comprehensive review of existing literature was conducted, focusing on molecular features of CAFGs in GC. Single-cell RNA sequencing (scRNA-seq) analyses were examined to assess the expression patterns of CAFGs in broad-sense CAFs, which include both CAFs and pericytes. Additionally, clinicopathological studies validating the prognostic significance of CAFGs were reviewed. Results: ScRNA-seq analyses revealed that CAFGs are not necessarily restricted to CAFs alone but may also reflect the activation status of surrounding cells. Several CAFGs, including SPARC, THBS2, COL1A1, COL3A1, INHBA, PDGFC, and SDC2, have been validated for their prognostic relevance in GC. However, compared with other cancers, the functional mechanisms of these genes in GC remain poorly understood. While CAFGs exhibit synchronized expression with TGFB1 in colorectal cancer (CRC), such patterns have yet to be confirmed in GC due to the limitations of available microdissected data. Conclusions: A comprehensive understanding of CAFGs and their interaction with the TGFB pathway, including LTBP family genes, may be critical for developing novel therapeutic strategies for GC. Further research is needed to elucidate their functional mechanisms and therapeutic potential.