Abstract
BACKGROUND: This study sought to examine the expression levels and clinical relevance of fibroblast activation protein alpha (FAP), caveolin-1 (CAV1), and carboxypeptidase X member 2 (CPXM2) in gastric cancer (GC) and adjacent tissues. METHODS: Multiplex immunofluorescence (mIF) was performed on tissue microarrays to evaluate the expression of FAP, CAV1, CPXM2, and cytokeratin (CK) in GC specimens. Correlations among these markers and their associations with clinicopathological features and survival outcomes were analyzed. RESULTS: This investigation discovered that CAV1 was predominantly expressed in stromal cells, whereas CPXM2 was expressed in both epithelial and stromal cells. The number and proportion of FAP(+) and CAV1(+) cells were significantly higher in GC tissues than in adjacent tissues, whereas CPXM2(+) cells were significantly reduced, and there was no significant difference in CK(+) cells. We employed CK to differentiate epithelial cells from stromal cells and found that there was no notable difference in the counts and proportion of CPXM2(+) cells between epithelial and stromal cells in GC tissues. Further research revealed that, in comparison with adjacent tissues, the number and proportion of CPXM2(+) cells in epithelial cells of GC tissues were significantly reduced. FAP was utilized as a marker for cancer associated fibroblasts (CAFs) in subsequent analyses. Additional investigations demonstrated that the counts and proportion of CAV1(+) cells in CAFs were notably increased in GC tissues, while there was no significant difference in CPXM2(+) cells. A strong positive correlation was observed between CAV1(+) and CPXM2(+) cells in GC tissues. Correlation analysis of clinicopathological parameters indicated that the proportion of FAP(+) cells correlated with AJCC stage and tumor invasion depth; CPXM2(+) cells correlated with tumor location; Epithelial CPXM2(+) cells were associated with the patient's age. CAFs with CAV1(+) and CPXM2(-)CAV1(+) cells were linked to the AJCC stage, invasion depth, and tumor location. Higher proportions of FAP(+), FAP(+)CAV1(+), and FAP(+)CPXM2(-)CAV1(+) cells were associated with poorer overall survival (OS). CONCLUSIONS: These findings suggest that CAV1 and CPXM2 are differentially expressed in GC and associated with patient prognosis, highlighting them as potential candidates for further functional investigation in the context of GC progression.