A Metastasis-Related lncRNA Signature Correlates With the Prognosis in Clear Cell Renal Cell Carcinoma

• Main Authors: Qian Dou, Shun Gao, Hua Gan, Zhao Kang, Han Zhang, Yichun Yang, Hang Tong
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-06-01
• Series: Frontiers in Oncology
• Subjects: clear cell renal cell carcinoma; metastasis; lncRNA; prognostic signature; EMT
• Online Access: https://www.frontiersin.org/articles/10.3389/fonc.2021.692535/full

To explore the role of metastasis-related long noncoding RNA (lncRNA) signature for predicting the prognosis of clear cell renal cell carcinoma (ccRCC) patients. Firstly, metastasis-associated genes were identified to establish a metastasis-related lncRNA signature by statistical analysis. Secondly, the ccRCC patients were grouped into high-risk or low-risk group according to the established signature, and the different pathways between the 2 groups were identified by gene set enrichment analysis (GSEA). Finally, investigations involving PCR, transwell migration and invasion assay were carried out to further confirm our findings. The metastasis-related lncRNA signature was successfully constructed according to 7-metastasis-related genes (ADAM12, CD44, IL6, TFPI2, TGF-β1, THBS2, TIMP3). The diagnostic efficacy and the clinically predictive capacity of the signature were evaluated. Most of the values of the area under the time‐dependent receiver‐operating characteristic (ROC) were greater than 0.70. The nomogram constructed by integrating clinical data and risk scores confirmed that the risk score calculated from our signature was a good prognosis predictor. GSEA analysis showed that some tumor-related pathways were enriched in the high-risk group, while metabolism-related pathways were enriched in the low-risk group. In carcinoma tissues, the SSR3-6, WISP1-2 were highly expressed, but the expression of UBAC2-6 was low there. Knocking down SSR3-6 decreased the ability of migration and invasion in ccRCC cells. In conclusion, we successfully constructed a metastasis-related lncRNA signature, which could accurately predict the survival and prognosis of ccRCC patients.