J Cancer 2019; 10(5):1237-1251. doi:10.7150/jca.28662 This issue

Research Paper

Overexpression of FZD1 is Associated with a Good Prognosis and Resistance of Sunitinib in Clear Cell Renal Cell Carcinoma

Qiang Peng1,2*, Lu Wang1,2*, Danfeng Zhao1,2*, Yulin Lv1, Hongzhi Wang1, Guang Chen1, Jiaqi Wang1,2, Wanhai Xu1,2✉

1. Department of Urology, the Fourth Hospital of Harbin Medical University, Harbin Medical University, Harbin, P. R. China.
2. Heilongjiang Key Laboratory of Scientific Research in Urology, Harbin, P. R. China.
*These authors contributed equally to this work.

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Peng Q, Wang L, Zhao D, Lv Y, Wang H, Chen G, Wang J, Xu W. Overexpression of FZD1 is Associated with a Good Prognosis and Resistance of Sunitinib in Clear Cell Renal Cell Carcinoma. J Cancer 2019; 10(5):1237-1251. doi:10.7150/jca.28662. Available from https://www.jcancer.org/v10p1237.htm

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Frizzled class receptor 1 (FZD1), a receptor for Wnt signaling pathway. Overexpression of FZD1 has been detected in many cancer tissues and cells resulting in tumor development and drug resistance. However, its expression status and prognostic merit in renal cancer still remains unclear. We screened the FZD1 mRNA in clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) from TCGA database and Oncomine database. We then detected FZD1 mRNA expression in sunitinib-resistant cells and the corresponding parental cells by qRT-PCR. FZD1 level was significantly upregulated in renal cancer tissues, renal cancer cell lines and their corresponding sunitinib-resistant cells. FZD1 level was also associated with the clinicopathological characteristics of ccRCC patients that could discriminate metastasis, pathological stage, recurrence and prognosis in ccRCC patients. The Kaplan-Meier survival curve and the log-rank test revealed FZD1 was higher in lower clinical stage and grade that correlated with better overall survival (OS) and disease-free survival (DFS) in total and subgroups of ccRCC patients. Both univariate and multivariate cox regression analysis indicated that high FZD1 level was an independent predictor of good prognosis for OS (HR 0.569, P=0.001) and DFS (HR 0.559, P=0.036) in ccRCC patients. Using cBioportal program, less than 1% mutation in the patients with renal cancer was observed, the alterations in FZD1 were correlated with better OS (P=0.0404) in ccRCC patients. Finally, the result of KEGG pathway analysis predicted seven potential pathways that FZD1 and its related genes got involved in ccRCC, including Hippo signaling pathway. This indicated potential therapeutic targets of ccRCC. In conclusion, our results suggested that expression status of FZD1 had a diagnostic value and prognostic value in ccRCC patients, it also may serve as a potential drug target to relieve sunitinib resistance in renal cancer patients.

Keywords: FZD1, clear cell renal cell carcinoma, drug-resistance, papillary renal cell carcinoma, prognosis