Downregulation of ENSG00000241684 is associated with poor prognosis in advanced clear cell renal cell carcinoma
Renal cell carcinoma(RCC) is the third most common genitourinary cancer and accounts for about 2% of all cancers. However, it is difficult to differentiate precisely advanced and localized ccRCC without tumor biopsy and histopathological classification. In order to identify potential novel biomarkers of advanced clear cell renal carcinoma (ccRCC), we re-evaluated published long non-coding RNA (lncRNA) expression profiling data.
The lncRNA expression profiles in ccRCC microarray dataset GSE47352 were analyzed including the expression of 2448 lncRNA transcripts in localized (stage I and II, n=5) and advanced (stage III and IV, n=4) ccRCC tissues. An independent cohort of 61 clinical samples including 21 advanced and 40 localized ccRCC patients was used to confirm the most statistically significant lncRNAs by real time PCR. Next, the relationships between the selected lncRNAs and ccRCC patients’ clinicopathological features were investigated. The effects of LncRNAs on the invasion and proliferation of renal carcinoma cells were also investigated.
The PCR results in a cohort of 21 advanced ccRCC and 40 localized ccRCC tissues were used for confirmation of eight selected lncRNAs(ENSG00000241684, ENSG00000235501, ENSG00000231721, ENSG00000214145, NEAT1, ENSG00000244020, PSORS1C3, H19) which were statistically most significant in GSE47352. The PCR results showed that the expression of three LncRNA (ENSG00000241684, ENSG00000231721 and NEAT1) were significantly downregulated in advanced ccRCC. Kaplan–Meier analysis revealed that reduced expression of LncRNA ENSG00000241684 and NEAT1 were significantly associated with poor overall survival. The univariate and multivariate Cox regression indicated LncRNA ENSG00000241684 had significant hazard ratios for predicting clinical outcome. LncRNA ENSG00000241684 expression was negatively correlated with pTNM stage. Overexpression of ENSG00000241684 significantly impaired cell proliferation and reduced the invasion ability in 786-O and ACHN cells.
lncRNAs are involved in renal carcinogenesis and decreased lncRNA ENSG00000241684 expression may be an independent adverse prognostic factor in advanced ccRCC patients.
Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 81602222 and 81572621). All these study sponsors have no roles in the study design, in the collection, analysis, and interpretation of data.