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微小RNA 211表达上调与结直肠癌预后不良相关:一项病例对照研究

MicroRNA 211 expression is upregulated and associated with poor prognosis in colorectal cancer: a case-control study.

作者信息

Sümbül Ahmet Taner, Göğebakan Bülent, Bayram Süleyman, Batmacı Celal Yücel, Öztuzcu Serdar

机构信息

Department of Medical Oncology, Baskent University, Adana, Turkey.

Department of Biology and Genetics, Mustafa Kemal University, Hatay, Turkey.

出版信息

Tumour Biol. 2015 Dec;36(12):9703-9. doi: 10.1007/s13277-015-3708-4. Epub 2015 Jul 8.

Abstract

Increasingly more evidence support the role of the microRNAs (miRNA) in tumorigenesis. The role of up/downregulation microRNA-211 (miR-211) during human tumorigenesis is still contentious and may exhibit tissue-specific regulatory manner, but the exhaustive mechanisms underlying its pro/anti-oncogenic effects remain to be unknown. Sixty-six patients that were diagnosed and operated with colorectal cancer (CRC) and sixty-five healthy cases that were age and sex compatible with them were included in our study. miRNA was isolated from the formalin-fixed paraffin-embedded (FFPE) tissues of all cases. The expression level of miR-211 in matched normal and tumor tissues of CRC group and healthy group was evaluated using a quantitative real-time RT-PCR (qRT-PCR). Based on the average miR-211 levels, two groups of low or high expression were formed in CRC group. Correlation of the patients' clinicopathological factors and survival was also analyzed. No statistically significant differences were found in miR-211 levels among tumorous and normal tissues of CRC patient group (P = 0.59). Also, no statistically significant correlation was determined between clinicopathological factors and miR-211 expression level in CRC group. However, miR-211 expression levels between the CRC group and the healthy group were determined to be of statistical significance (P < 0.0001). There were 33 (50 %) CRC patients that expressed low levels of miR-211 and 33 (50 %) CRC patients that expressed high levels of miR-211. A median survival between low levels of miR-211 group and high levels of miR-211 group was evaluated via Kaplan-Meier, and the difference was of statistical significance (P = 0.035). The univariate analysis of the factors that may affect survival indicated invasion depth (P = 0.063), lymphovascular invasion (P = 0.011), perineural invasion (P = 0.009), and miR-211 expression level (P = 0.041) presence to be effective. In the multivariate analysis of these factors with overall survival, only miR-211 expression level (P = 0.01) was effective on overall survival. Our results suggest for the first time that miR-211 expressed more in CRC patients than in healthy group could be a new prognostic biomarker in order to predict survival. Independent studies are needed to validate our findings in a larger series, as well as in cancer of different tissues.

摘要

越来越多的证据支持微小RNA(miRNA)在肿瘤发生中的作用。人肿瘤发生过程中上调/下调微小RNA-211(miR-211)的作用仍存在争议,可能表现出组织特异性调控方式,但其促癌/抑癌作用的详尽机制仍不清楚。我们的研究纳入了66例经诊断并接受手术的结直肠癌(CRC)患者以及65例年龄和性别与之匹配的健康对照。从所有病例的福尔马林固定石蜡包埋(FFPE)组织中分离miRNA。采用定量实时RT-PCR(qRT-PCR)评估CRC组和健康组配对的正常组织和肿瘤组织中miR-211的表达水平。根据miR-211的平均水平,CRC组分为低表达或高表达两组。还分析了患者临床病理因素与生存的相关性。CRC患者组的肿瘤组织和正常组织中miR-211水平无统计学显著差异(P = 0.59)。此外,CRC组临床病理因素与miR-211表达水平之间未确定有统计学显著相关性。然而,CRC组与健康组之间的miR-211表达水平有统计学显著差异(P < 0.0001)。有33例(50%)CRC患者miR-211表达水平低,33例(50%)CRC患者miR-211表达水平高。通过Kaplan-Meier评估miR-211低表达组和高表达组之间的中位生存期,差异有统计学意义(P = 0.035)。对可能影响生存的因素进行单因素分析表明,浸润深度(P = 0.063)、淋巴管浸润(P = 0.011)、神经周围浸润(P = 0.009)和miR-211表达水平(P = 0.041)均有影响。在对这些因素与总生存期的多因素分析中,只有miR-211表达水平(P = 0.01)对总生存期有影响。我们的结果首次表明,CRC患者中miR-211表达高于健康组,这可能是一种预测生存的新的预后生物标志物。需要独立研究在更大样本系列以及不同组织的癌症中验证我们的发现。

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