Abstract
One-third of clear cell renal cell carcinoma (ccRCC) patients present with metastasis at the time of diagnosis. The prognosis of these patients is poor. To identify potential prognostic biomarkers and therapeutic targets for ccRCC, we re-evaluated published long non-coding RNA (lncRNA) expression profiling data from the Gene Expression Omnibus and ArrayExpress database. We found that five lncRNAs were differentially expressed in ccRCC and adjacent tissues. These lncRNAs were assessed in an independent cohort of 71 paired patient samples using real-time PCR. Differences in expression of three of the lncRNAs (ENSG00000177133, TCL6, and ENSG00000244020) were validated in this analysis. Kaplan-Meier analysis indicated that low expression of ENSG00000177133 and TCL6 was associated with a poor prognosis. Univariate and multivariate regression analyses demonstrated that TCL6 but not ENSG00000177133 expression was an independent predictor of ccRCC aggressiveness and had hazard ratios predictive of clinical outcome. TCL6 expression was negatively correlated with pTNM stage. Overexpression of TCL6 in 786-O and Caki-1 ccRCC cells decreased proliferation and increased apoptosis compared to controls. Our results indicate that lncRNA expression is altered in ccRCC and that decreased TCL6 expression may be an independent adverse prognostic factor in ccRCC patients.
Highlights
Renal cell carcinoma (RCC) is the third most common genitourinary cancer and accounts for approximately 3% of all cancers [1, 2]
We identified a series of differentially expressed long non-coding RNA (lncRNA) in clear cell RCC (ccRCC), which were validated in clinical samples by real-time PCR (RT-PCR)
We examined the expression of these lncRNAs in the E-TABM-282 dataset and confirmed differential expression of five lncRNAs: ENSG00000247225, ENSG00000241732, ENSG00000177133, ENSG00000244020, and TCL6
Summary
Renal cell carcinoma (RCC) is the third most common genitourinary cancer and accounts for approximately 3% of all cancers [1, 2]. 70% of all renal tumors are clear cell RCC (ccRCC) [3]. The identification of sensitive and specific ccRCC biomarkers and the development of new therapeutic approaches is essential. Microarrays and high-throughput RNA sequencing tools have facilitated the identification of long non-coding. RNAs (lncRNAs) that modulate gene expression [4]. Previous studies have indicated that lncRNAs play critical roles in malignant tumors including colorectal and ovarian cancer [5, 6]. The functions of lncRNAs in ccRCC development and metastasis have not been elucidated [7]
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