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鉴定失调的血清 miR-508-3p 和 miR-885-5p 作为透明细胞肾细胞癌的潜在诊断生物标志物。

Identification of dysregulated serum miR-508-3p and miR-885-5p as potential diagnostic biomarkers of clear cell renal carcinoma.

机构信息

Department of Urology, Zhoupu Hospital Affiliated with Shanghai University of Medicine and Health Sciences, Shanghai 200000, P.R. China.

Department of Urology, Shanghai Putuo District Liqun Hospital, Shanghai 200000, P.R. China.

出版信息

Mol Med Rep. 2019 Dec;20(6):5075-5083. doi: 10.3892/mmr.2019.10762. Epub 2019 Oct 22.

Abstract

Clear cell renal cell carcinoma (ccRCC), the most common subtype, accounts for approximately 80% of all RCC cases. ccRCC patients typically present with an advanced stage at the time of diagnosis resulting in a poor patient prognosis. The present study aimed to identify novel potential microRNAs (miRNAs or miRs) in peripheral blood as biomarkers for the detection of ccRCC. Candidate miRNAs were selected through integrated analysis of the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database, and from clinical samples. The expression levels of miRNAs were quantified using reverse transcription‑quantitative PCR. Receiver operating characteristic (ROC) curve analysis was used to explore the diagnostic values of the miRNAs. Bioinformatic analysis of candidate miRNAs was conducted by using the STRING database. After an integrated analysis of the GEO and TCGA databases, four miRNAs were found to be consistently dysregulated in ccRCC tissues. Then, their expression levels in serum and diagnostic utilities were further explored. We discovered that serum miR‑508‑3p and miR‑885‑5p were significantly dysregulated in ccRCC patients with marked diagnostic values. The area under the ROC curve (AUC) of serum miR‑508‑3p and miR‑885‑5p was 0.80 (95% CI, 0.73‑0.87) and 0.87 (95% CI, 0.79‑0.95), respectively. Functional enrichment analysis revealed that both miR‑508‑3p and miR‑885‑5p were closely associated with cellular metabolic processes. In conclusion, serum miR‑508‑3p and miR‑885‑5p are novel potential biomarkers for the diagnosis of ccRCC.

摘要

透明细胞肾细胞癌(ccRCC)是最常见的亚型,约占所有 RCC 病例的 80%。ccRCC 患者在诊断时通常处于晚期,导致患者预后较差。本研究旨在鉴定外周血中新型潜在 microRNAs(miRNAs 或 miRs)作为 ccRCC 检测的生物标志物。通过综合分析基因表达综合数据库(GEO)、癌症基因组图谱(TCGA)数据库和临床样本,选择候选 miRNAs。使用逆转录-定量 PCR 定量检测 miRNA 的表达水平。采用受试者工作特征(ROC)曲线分析探讨 miRNA 的诊断价值。通过 STRING 数据库对候选 miRNA 进行生物信息学分析。在对 GEO 和 TCGA 数据库进行综合分析后,发现 4 个 miRNA 在 ccRCC 组织中持续失调。然后,进一步探讨了它们在血清中的表达水平及其诊断效用。我们发现,miR-508-3p 和 miR-885-5p 在 ccRCC 患者血清中显著失调,具有显著的诊断价值。血清 miR-508-3p 和 miR-885-5p 的 ROC 曲线下面积(AUC)分别为 0.80(95%CI,0.73-0.87)和 0.87(95%CI,0.79-0.95)。功能富集分析表明,miR-508-3p 和 miR-885-5p 均与细胞代谢过程密切相关。总之,血清 miR-508-3p 和 miR-885-5p 是诊断 ccRCC 的新型潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37f/6854552/d377812fab16/MMR-20-06-5075-g00.jpg

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