POSTN is exclusively activated in cancer-associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer.

Drug resistance significantly impairs the prognosis of patients with gastric cancer (GC). As a key player in the acquisition of drug resistance, understanding the detailed evolution of the GC tumor microenvironment (TME) is crucial for improving therapeutic effectiveness. The clinical significance of markers related to cancer-associated fibroblast (CAF) proliferation and extracellular matrix remodeling were analyzed using public databases and immunohistochemistry staining on an in-house cohort of patients with GC. Combining this with single-cell RNA sequencing data revealed the expression patterns of all candidate markers, highlighting POSTN due to its pronounced upregulation in CAFs and its strong correlation with poor prognosis in patients with GC. Mechanistically, POSTN is directly regulated by the YAP1/TEAD1 co-transcription factor and is demonstrated to play significant roles in fibroblast proliferation and migration processes. The present study underscores POSTN as a promising marker for predicting GC prognosis and a powerful regulator that can augment the tumorigenic phenotypes of CAFs, providing a potential target to mitigate CAF-originated drug resistance.