The correlation of intratumoral fibrosis with the prognosis of clear cell renal cell carcinoma / 中华泌尿外科杂志

ABSTRACT

Objective:To investigate the correlation of intratumoral fibrosis with the prognosis of clear cell renal cell carcinoma (ccRCC).Methods:The correlation of the transcriptional expression of the primary collagen with the prognosis in ccRCC was evaluated using the Cancer Genome Atlas (TCGA) database, including 530 ccRCC patients with complete information. Of them, 344 cases were male, 186 cases were female. The age of 264 cases was ≤ 60 years, and the age of 266 cases was > 60 years. The pathology grade of 241 patients was G 1-2 grade, and the pathology of 281 cases were G 3-4 grade, 8 cases were undetermined grade. There were 322 cases with AJCC stage Ⅰ-Ⅱ and 205 cases with AJCC stage Ⅲ-Ⅳ, and 3 cases with undetermined stage. There were 420 cases in M 0 and 78 cases in M 1, and 32 cases without distant metastases information. Furthermore, the paraffin sections of 158 non-cystic ccRCC patients confirmed by pathology from November 2005 to November 2017 were further used to evaluate the level of collagen of ccRCC and the status of the pseudocapsule by the Masson staining, Sirius red staining and multicolor immunofluorescence staining of collagen Ⅰ and collagen Ⅲ. Of them, 112 cases were male, 46 cases were female. There were 100 cases with age ≤ 60 years, and 58 cases with age > 60 years. The pathology grade of 111 cases were G 1-2, and the pathology grade of 47 cases were G 3-4. There were 144 cases with AJCC stage Ⅰ-Ⅱ, 14 cases with AJCC stage Ⅲ-Ⅳ. Kaplan-Meier survival curve were used to analyze the relationship between tumor collagen parameters and the overall survival prognosis of patients with ccRCC. Results:The transcriptome results of the TCGA database indicated that the expression level of COL1A1 in ccRCC tissues was significantly higher than that in adjacent normal tissues ( P<0.001). The high expression of collagen suggested a worse overall survival prognosis ( HR=1.165, P=0.002). In addition, the high ratio of COL1A1/COL3A1 indicated a worse overall survival prognosis ( HR=1.901, P<0.001) compared with the low ratio. We further confirmed that the abundance of collagen in tumor was significantly increased compared with the normal adjacent tissues by the Masson staining [41.0 (14.0-75.0) vs.15.0 (3.0-57.0), P<0.001] and the Sirius red staining [42.5 (10.0-90.0) vs.10.0 (2.5-60.0), P<0.001] on 30 ccRCC tissues and adjacent normal tissues. Based on the Masson staining, we found that high collagen abundance in tumor tissue was associated with more G 3-4 grade of tumor compared with low collagen abundance (38.5% vs.21.3%, OR=2.316, 95% CI 1.146-4.681, P=0.023). Kaplan-Meier survival curve showed that higher collagen abundance was associated with a worse overall survival prognosis in ccRCC ( HR=2.630, P=0.007). However, incomplete fibrous pseudocapsule was associated with a worse overall survival prognosis ( HR=11.140, P<0.001). Conclusions:In ccRCC, intratumoral collagen fiber level was overexpressed. High intratumoral collagen level and incomplete fibrous pseudocapsule may indicate a poor overall survival prognosis.