Overexpression of COL5A1 promotes tumor progression and metastasis and correlates with poor survival of patients with clear cell renal cell carcinoma
Received 20 September 2018
Accepted for publication 13 January 2019
Published 7 February 2019 Volume 2019:11 Pages 1263—1274
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 3
Editor who approved publication: Professor Nakshatri
Gang Feng,1,2 Hui-Min Ma,1 Hou-Bao Huang,3 Ya-Wei Li,3 Peng Zhang,1 Jian-Jun Huang,1 Long Cheng,1,2 Guo-Rong Li4
1Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China; 2Anhui Province Key Laboratory of Active Biological Macro-molecules Research, Wannan Medical College, Wuhu 241002, Anhui, China; 3Department of Urology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China; 4Department of Urology, North Hospital, CHU of Saint-Etienne, Saint-Etienne 42055, France
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.
Keywords: clear cell renal cell carcinoma, COL5A1, biomarkers, prognosis
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