High expressions of CD10, FAP and GPR77 in CAFs are associated with chemoresistance and worse prognosis in gastric cancer

Abstract

IntroductionAs neoadjuvant chemotherapy (NCT) has been successfully introduced in gastric cancer (GC), more biomarkers are needed to evaluate the efficacy. Cancer-associated fibroblasts (CAFs) is associated with chemoresistance and prognosis. Three biomarkers, CD10, fibroblast activation protein-α (FAP) and G-protein-coupled receptor 77 (GPR77), have been proved to express in CAFs. However, their predictive values for efficacy of NCT and prognosis in gastric cancer is unknown.MethodsTotally, specimens of 171 locally advanced gastric cancer patients who underwent NCT and D2 radical gastrectomy and matched preoperative biopsy specimens were retrospectively analyzed. Tumor regression grade (TRG) is reevaluated according to Mandard TRG. Expressions of CD10, FAP and GPR77 in CAFs before NCT (pre-) and after NCT (post-) were evaluated by immunohistochemistry. Survival curves on overall survival (OS) were obtained by Kaplan-Meier method, and differences were analyzed by log-rank test. Associations between categorical variables were explored by chi-square test or Fisher’s exact method. Univariable and multivariate analyses were performed by logistic regression model and Cox proportional hazard regression model.ResultsHigh expressions of post-CD10, post-FAP, post-GPR77 and pre-CD10 were related to worse TRG (all p<0.05). In multivariable analysis, post- and pre-FAP were independent predictive factors to TRG (p<0.010). Post-CD10 (p=0.032) and post-FAP (p=0.013) were related to OS in univariable analysis, but none of biomarkers were independent prognostic factors in multivariable analysis.ConclusionsExpressions of CD10, FAP and GPR77 in CAFs were related to chemoresistance and overall survival, and these biomarkers have predictive values for tumor regression and prognosis in locally advanced gastric cancer patients.

What is new in cancer-associated fibroblast biomarkers?

“…It is associated with poor prognosis of NSCLC [ 14 ], gastric cancer [ 10 ], CCRCC [ 12 ], ovarian cancer [ 13 ], and bladder high-grade UC [ 8 ], but not cervical cancer [ 15 ]. FAP + CAFs are independent predictive factors to worse tumor regression grade (TRG), that means chemoresistance in gastric cancer [ 16 ].…”

Unraveling the prognostic significance of RGS gene family in gastric cancer and the potential implication of RGS4 in regulating tumor-infiltrating fibroblast

“…Previous studies have shown that the main function of FGF2 is related to cell adhesion and angiogenesis, and patients with high FGF2 expression level have poor TNM stage and prognosis ( Li Y. et al, 2020 ). Zhao et al found that Twist1 was an independent factor affecting the pathological response to neoadjuvant chemotherapy for gastric cancer, and the expression of FAP in CAF was a significant factor for poor prognosis in patients with gastric cancer ( Tong et al, 2022 ; Zhao and Zhu, 2023 ). The expression of PDGFB has been reported to be closely related to tumor metastasis in patients with gastric cancer ( Han et al, 2020 ; Du et al, 2022 ).…”

Enhancement of PD-L1-attenuated CAR-T cell function through breast cancer-associated fibroblasts-derived IL-6 signaling via STAT3/AKT pathways

“…Targeting the CD10 + GPR77 + CAFs subset retards tumor formation and reverses chemoresistance by destroying the CSC niches [ 27 , 36 ]. CD10 + GPR77 + FAP + CAFs were associated with chemoresistance and overall survival of advanced gastric cancer patients who underwent neoadjuvant chemotherapy (NCT) [ 37 ]. FAP increasing drug resistance are various, such as promoting immunosuppression and producing chemokine [ 37 ].…”

“…CD10 + GPR77 + FAP + CAFs were associated with chemoresistance and overall survival of advanced gastric cancer patients who underwent neoadjuvant chemotherapy (NCT) [ 37 ]. FAP increasing drug resistance are various, such as promoting immunosuppression and producing chemokine [ 37 ]. CD10 and GPR77 have been proven to promote cancer formation and chemoresistance by providing a survival niche for CSCs and promoting an epithelial-mesenchymal transition [ 37 ].…”

“…FAP increasing drug resistance are various, such as promoting immunosuppression and producing chemokine [ 37 ]. CD10 and GPR77 have been proven to promote cancer formation and chemoresistance by providing a survival niche for CSCs and promoting an epithelial-mesenchymal transition [ 37 ]. In addition, CAFs affect the chemotherapy through an increased interstitial fluid pressure forming a barrier to the transcapillary transport of drugs from blood vessels to cancer cells [ 38 ].…”