Identification and validation of the clinical roles of the VHL-related LncRNAs in clear cell renal cell carcinoma

Yang, Wuping; Zhou, Jingcheng; Zhang, Kenan; Li, Lei; Xu, Yawei; Ma, Kaifang; Xie, Haibiao; Cai, Lin; Gong, Yanqing; Gong, Kan

doi:10.7150/jca.55113

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J Cancer 2021; 12(9):2702-2714. doi:10.7150/jca.55113 This issue Cite

Research Paper

Identification and validation of the clinical roles of the VHL-related LncRNAs in clear cell renal cell carcinoma

Wuping Yang^1,2,3,4, Jingcheng Zhou^1,2,3,4, Kenan Zhang^1,2,3,4, Lei Li^1,2,3,4, Yawei Xu^1,2,3,4, Kaifang Ma^1,2,3,4, Haibiao Xie^1,2,3,4, Lin Cai^1,2,3,4, Yanqing Gong^1,2,3,4✉, Kan Gong^1,2,3,4✉

1. Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.
2. Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.
3. Institute of Urology, Peking University, Beijing 100034, P.R. China.
4. National Urological Cancer Center, Beijing 100034, P.R. China.

Citation:

Yang W, Zhou J, Zhang K, Li L, Xu Y, Ma K, Xie H, Cai L, Gong Y, Gong K. Identification and validation of the clinical roles of the VHL-related LncRNAs in clear cell renal cell carcinoma. J Cancer 2021; 12(9):2702-2714. doi:10.7150/jca.55113. https://www.jcancer.org/v12p2702.htm

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Abstract

Accumulating evidence suggests that lncRNAs (long non-coding RNAs) function as oncogenes or tumor suppressor genes in ccRCC (clear cell renal cell carcinoma). Although VHL (Von Hippel-Lindau) gene inactivation is by far the most common carcinogenic driving event in ccRCC, the roles of VHL-related lncRNAs in ccRCC remain unknown. In this study, using RNA-seq and clinical data in TCGA-KIRC (the Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma), we identified VHL-related lncRNAs through WGCNA (Weighted Gene Co-expression Network Analysis), correlation analysis and catRAPID algorithm, and explored their clinical characteristics in ccRCC. Results showed that 10 lncRNAs (AC112220.2, AL391121.1, USP46-AS1, AL450326.1, MID1IP1-AS1, SUCLG2-AS1, RAP2C-AS1, FGD5-AS1, AC018647.2 and AC015922.2) were identified as VHL-related lncRNAs, and they were down-regulated in ccRCC tissues. Survival analysis results indicated that high expression groups of AC112220.2, AL391121.1, USP46-AS1, AL450326.1, SUCLG2-AS1, RAP2C-AS1, FGD5-AS1, AC018647.2 and AC015922.2 had significantly longer OS (Overall Survival) than their respective low expression groups. Meanwhile high AC112220.2, USP46-AS1, AL450326.1, SUCLG2-AS1, FGD5-AS1, AC018647.2 and AC015922.2 expression groups had remarkably longer DFS (Disease Free Survival) than their respective low expression groups. Besides, FGD5-AS1 and AL391121.1 expression were decreased in VHL mutant tissues compared with VHL non-mutant tissues. Moreover, high expression group of FGD5-AS1 had significantly longer OS and DFS than their respective low expression groups in VHL mutant ccRCC. In addition, we found that DNA hypermethylation may also play an important role in decreased FGD5-AS1 expression. Furthermore, we validated the expression of FGD5-AS1 in VHL mutant and non-mutant ccRCC tissues and cell lines. In conclusion, our results demonstrated that lncRNA FGD5-AS1 was significantly associated with VHL and can serve as a novel biomarker of ccRCC.

Keywords: VHL, lncRNAs, ccRCC, FGD5-AS1, survival

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APA

Yang, W., Zhou, J., Zhang, K., Li, L., Xu, Y., Ma, K., Xie, H., Cai, L., Gong, Y., Gong, K. (2021). Identification and validation of the clinical roles of the VHL-related LncRNAs in clear cell renal cell carcinoma. Journal of Cancer, 12(9), 2702-2714. https://doi.org/10.7150/jca.55113.

ACS

Yang, W.; Zhou, J.; Zhang, K.; Li, L.; Xu, Y.; Ma, K.; Xie, H.; Cai, L.; Gong, Y.; Gong, K. Identification and validation of the clinical roles of the VHL-related LncRNAs in clear cell renal cell carcinoma. J. Cancer 2021, 12 (9), 2702-2714. DOI: 10.7150/jca.55113.

NLM

CSE

Yang W, Zhou J, Zhang K, Li L, Xu Y, Ma K, Xie H, Cai L, Gong Y, Gong K. 2021. Identification and validation of the clinical roles of the VHL-related LncRNAs in clear cell renal cell carcinoma. J Cancer. 12(9):2702-2714.

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