Abstract: Objective To analyze the typical biomarker of cancer-related fibroblasts-fibroblast activation protein-α(FAP) expression in tumor tissue and perinephric adipose tissue and its clinical value in risk stratification of clear cell renal cell carcinoma(ccRCC).Methods A retrospective cross-sectional study was conducted on ccRCC patients who underwent nephrectomy in Dongfeng General Hospital of Sinopharm Affiliated to Hubei Medical College from June 2018 to September 2022.The expression of FAP in ccRCC renal tumor tissue(n=114),non-neoplastic renal cortex tissue(n=68) and perirenal adipose tissue(n=60) was detected by immunohistochemical staining,and immunohistochemical images were quantitatively analyzed.The benign adipose tissue around the kidneys from 19 patients with benign kidney disease were collected as a control group, and also detect FAP expression. Receiver operating characteristic (ROC) curves was used to analyze the ability of FAP expression in perirenal adipose tissue to diagnose ccRCC and predict distant metastasis.Results Compared with matched non-neoplastic renal tissues,the expression of FAP in ccRCC was not up-regulated.The receiver operating characteristic(ROC) curve analysis showed that the percentage of FAP positive staining in ccRCC tissue had good tumor clinical stage,tumor size and distant metastasis potential(P＜0.001),and the area under the curve(AUC) were 0.90(95%CI:0.81-0.98),0.79(95%CI:0.66-0.92) and 0.86(95%CI:0.74-0.99),respectively.The percentage of FAP positive staining in perinephric adipose tissue of ccRCC can predict distant metastasis,and the AUC is 0.91(95%CI:0.84～0.97).The staining intensity of FAP expression in perinephric adipose tissue of ccrcc(191.77±3.14 vs.188.90±2.89,P＜0.001) was slightly higher than that of benign renal disease,and the staining intensity of FAP in perinephric adipose tissue had a certain distinguishing value for benign and malignant renal tumors,with AUC of 0.68(95%CI:0.60～0.77).Conclusion FAP in tumor and perinephric adipose tissue is expected to be one of the effective indicators of ccrcc risk stratification.

Key words: clear cell renal cell carcinoma, fibroblast activation protein- α, tumor aggressiveness, perinephric adipose tissue