长链非编码 RNA ENSG00000241684 的下调与晚期透明细胞肾细胞癌的不良预后相关。

Downregulation of long non-coding RNA ENSG00000241684 is associated with poor prognosis in advanced clear cell renal cell carcinoma.

机构信息

Department of Urology, Fudan University Shanghai Cancer Center, 200025, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, 200025, Shanghai, China.

Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 200025, Shanghai, China.

出版信息

Eur J Surg Oncol. 2018 Jun;44(6):840-846. doi: 10.1016/j.ejso.2018.01.013. Epub 2018 Jan 13.

DOI:10.1016/j.ejso.2018.01.013

PMID:29433989

Abstract

OBJECTIVE

In order to identify potential novel biomarkers of advanced clear cell renal cell carcinoma (ccRCC), we re-evaluated published long non-coding RNA (lncRNA) expression profiling data.

MATERIALS AND METHODS

The lncRNA expression profiles in ccRCC microarray dataset GSE47352 were analyzed and 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.

RESULTS

The PCR results in a cohort of 21 advanced ccRCC and 40 localized ccRCC tissues were used for confirmation of the selected lncRNAs which were statistically most significant. 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.

CONCLUSION

lncRNAs are involved in renal carcinogenesis and decreased lncRNA ENSG00000241684 expression may be an independent adverse prognostic factor in advanced ccRCC patients.

摘要

目的

为了鉴定晚期透明细胞肾细胞癌（ccRCC）的潜在新型生物标志物，我们重新评估了已发表的长非编码 RNA（lncRNA）表达谱数据。

材料与方法

分析 ccRCC 微阵列数据集 GSE47352 中的 lncRNA 表达谱，并使用包含 21 例晚期和 40 例局限性 ccRCC 患者的独立队列通过实时 PCR 来验证最具有统计学意义的 lncRNA。然后，研究了所选 lncRNA 与 ccRCC 患者临床病理特征之间的关系。还研究了 LncRNA 对肾癌细胞侵袭和增殖的影响。

结果

对 21 例晚期 ccRCC 和 40 例局限性 ccRCC 组织的队列进行 PCR 验证，用于确认具有统计学意义的最显著的 lncRNA。PCR 结果表明，三种 LncRNA（ENSG00000241684、ENSG00000231721 和 NEAT1）在晚期 ccRCC 中表达明显下调。Kaplan-Meier 分析显示，LncRNA ENSG00000241684 和 NEAT1 表达降低与总生存期不良显著相关。单变量和多变量 Cox 回归表明，LncRNA ENSG00000241684 对预测临床结局具有显著的危险比。LncRNA ENSG00000241684 的表达与 pTNM 分期呈负相关。ENSG00000241684 的过表达显著抑制了 786-O 和 ACHN 细胞的增殖，并降低了其侵袭能力。