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miR-183 和 miR-21 的表达作为舌癌患者进展和生存的生物标志物。

miR-183 and miR-21 expression as biomarkers of progression and survival in tongue carcinoma patients.

机构信息

Faculty of Medicine, Military Medical Academy, University of Defense, Belgrade, Serbia.

Institute for Medical Research, Military Medical Academy, Crnotravska 17, Belgrade, 11002, Serbia.

出版信息

Clin Oral Investig. 2018 Jan;22(1):401-409. doi: 10.1007/s00784-017-2126-y. Epub 2017 Jun 14.

Abstract

OBJECTIVES

Micro RNAs (miRNAs) have a major role in human cancerogenesis.The current study investigated the prognostic significance of miR-183 and miR-21 expression in tongue carcinoma patients.

MATERIAL AND METHOD

For qPCR of miR-183 and miR-21 expression, total RNA isolated from 60 fresh-frozen tissue of tongue carcinomas was converted into cDNA by TaqMan MicroRNA Reverse Transcription Kit and quantified by TaqMan MicroRNAs Expression Assays. Fold changes in the miRNAs expression, normalized to RNU6B, were determined using 2 method, and dichotomized into high and low according to cut-off values derived from ROC curve analysis.

RESULTS

miR-183 emerged as promising discriminatory biomarker of poor outcome. Tissue over-expression of miR-183, observed in 68.3% of tongue carcinomas, was associated with clinical stage (p = 0.037), tumor size (p = 0.036), and high alcohol intake (p = 0.034).The patients with miR-183 over-expression had significantly shorter overall survival (p = 0.006) and a 5.666 times higher risk of poor outcome (p = 0.005), while miR-21 over-expression carried a tendency towards poorer survival (p = 0.073). However, multivariate analysis revealed that the recurrences were independent adverse prognostic factors, while miR-183 over-expression lost its significance.

CONCLUSION

Our results suggests that over-expression of miR-183 in tumor tissue could be a potential marker of clinical stage and a poor survival of tongue carcinoma patients and may be associated with high alcohol consumption.

CLINICAL RELEVANCE

Oncogenic miRNAs, such as the investigated miR-183 and miR-21, could be novel prognostic biomarkers of tumor progression and adverse clinical outcome in oral cancer, as well as novel therapeutic targets in cancer.

摘要

目的

微小 RNA(miRNA)在人类癌症发生中起主要作用。本研究调查了 miR-183 和 miR-21 表达在舌癌患者中的预后意义。

材料和方法

为了进行 miR-183 和 miR-21 表达的 qPCR,从 60 例新鲜冷冻的舌癌组织中分离总 RNA,通过 TaqMan MicroRNA 逆转录试剂盒将其转化为 cDNA,并通过 TaqMan MicroRNAs Expression Assays 进行定量。使用 2 法确定 miRNA 表达的倍数变化,并根据 ROC 曲线分析得出的截断值将其分为高表达和低表达。

结果

miR-183 成为预后不良的有前途的鉴别生物标志物。在 68.3%的舌癌中观察到 miR-183 的组织过表达与临床分期(p=0.037)、肿瘤大小(p=0.036)和高酒精摄入(p=0.034)有关。miR-183 过表达的患者总生存时间明显缩短(p=0.006),预后不良的风险高 5.666 倍(p=0.005),而 miR-21 过表达则有较差的生存趋势(p=0.073)。然而,多变量分析显示复发是独立的不良预后因素,而 miR-183 过表达失去了其意义。

结论

我们的结果表明,肿瘤组织中 miR-183 的过表达可能是舌癌患者临床分期和生存不良的潜在标志物,并且可能与高酒精摄入有关。

临床相关性

致癌 miRNA,如研究的 miR-183 和 miR-21,可能是口腔癌肿瘤进展和不良临床结局的新型预后生物标志物,也是癌症的新型治疗靶点。

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