Overexpression of COL5A1 promotes tumor progression and metastasis and correlates with poor survival of patients with clear cell renal cell carcinoma

Background and aims: COL5A1 has been identified to be involved in metastasis of clear cell renal cell carcinoma (ccRCC) by bioinformatic analysis. This study aimed to investigate COL5A1 expression and its clinical significance in ccRCC. The function of COL5A1 in ccRCC was further investigated.

Methods: COL5A1 expression was examined in 256 ccRCC tissues and paired adjacent normal renal tissues by immunohistochemistry and real-time quantitative PCR. The clinical significance of COL5A1 expression was evaluated. Downregulation of COL5A1 was achieved using siRNA. The effects of COL5A1 silencing on cell proliferation, apoptosis, migration, invasion in vitro, and tumor growth in vivo were investigated.

Results: COL5A1 expression was upregulated in the majority of the ccRCC tissues at both protein and mRNA levels. COL5A1 expression was significantly correlated with tumor diameter, tumor stage, tumor grade, distant metastasis, recurrence, necrosis, and sarcomatoid (all P<0.05). COL5A1 expression was also significantly associated with overall survival of ccRCC patients (HR 1.876; P=0.027) and recurrence-free survival of localized ccRCC patients (HR 4.751; P<0.001). The accuracy of TNM, University of California Los Angeles Integrated Staging System, and Mayo clinic stage, size, grade, and necrosis prognostic models was improved when COL5A1 expression was added.

Conclusion: COL5A1 knockdown significantly inhibited cell proliferation, induced cell apoptosis, inhibited cell migration and invasion in vitro, and inhibited tumor growth in vivo. Therefore, COL5A1 may be a novel prognostic biomarker and a promising therapeutic target for ccRCC.