Assessment of tumor-associated fibroblast as a biomarker for predicting recurrence of non-muscle invasive bladder cancer

Abstract:

Objective To investigate the clinical significance of tumor-associated fibroblast as a biomarker in predicting postoperative recurrence of non-muscle invasive bladder cancer（NMIBC）.Methods Transcriptomic data were downloaded from the Gene Expression Omnibus database along with corresponding clinical information to analyze the differences in ACTA2 expression in primary and recurrent bladder cancer samples. Immunohistochemistry（IHC） was used to determine α-smooth muscle actin（α-SMA） expression in 56 bladder cancer samples. Recurrence-free survival（RFS） curves and time-dependent receiver operating characteristic（tdROC） curves were plotted. Univariate and multivariate Cox proportional hazard regression models were used to analyze the feasibility of α-SMA as a predictor of postoperative recurrence of bladder cancer.Results The expression of ACTA2 was significantly higher in the recurrence group than in the primary group in the GSE13507，GSE120739，and GSE128959 datasets（P<0.05）. IHC results showed that α-SMA protein was localized in the tumor stoma，and the percentage of positive/strongly positive α-SMA was 56.52% in the recurrence group and 16.13% in the primary group，with a significant difference between the two groups（P<0.001）. There was no significant correlation between α-SMA protein expression and age，gender，pathological stage，grade，tumor number，and size. Postoperative RFS was significantly shorter in patients with high α-SMA expression than in those with low α-SMA expression [hazard ratio（HR）=2.76，95% confidence interval（CI）=1.21~6.30，P=0.016]. Multivariate Cox analysis showed that α-SMA protein expression level was an independent risk factor for postoperative RFS in patients（HR=2.47，95%CI=1.02~5.97，P=0.045）. tdROC curves suggested that α-SMA was a better predictor of recurrence than other clinical factors.Conclusion α-SMA protein expression level in the tumor stroma is closely related to the recurrence of bladder cancer and can be used as a clinical marker to predict postoperative recurrence of NMIBC.