Kim Mi Kyeong, Jung Sang Bong, Kim Jong-Sik, Roh Mee Sook, Lee Ji Hyun, Lee Eun Hee, Lee Hyoun Wook
Department of Clinical Laboratory Science, Gimhae College, Gimhae, South Korea.
Virchows Arch. 2014 Oct;465(4):463-71. doi: 10.1007/s00428-014-1640-4. Epub 2014 Aug 16.
MicroRNAs (miRNAs) are short non-coding RNAs that exert a critical influence on tumorigenesis through post-transcriptional modification and are considered to be potential biomarkers for the diagnosis or prognosis of various cancers. Although several miRNAs have been proposed as relevant biomarkers for non-small cell lung cancer (NSCLC), detailed working mechanisms and validated prognostic significance of these miRNAs remain controversial. In this study, we evaluated expression levels of miRNA-126 (miR-126) and miR-200c in 72 NSCLCs and 30 benign lung tissues by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and analyzed the correlation of miRNA expression with a variety of clinicopathological factors and patient survival. Compared with the benign control group, miR-126 expression was significantly downregulated in NSCLCs (p < 0.001), while miR-200c expression was significantly upregulated in NSCLCs (p < 0.001). The expression of miR-126 was significantly higher in NSCLCs with a tumor size of ≤3 cm than in those with a tumor size of >3 cm (p = 0.026). There were no other significant associations between miRNA expression and clinicopathological features. In univariate survival analysis for all NSCLC patients, high miR-200c expression (p = 0.037), large tumor size (p = 0.026), and lymphovascular invasion (p = 0.012) were significantly correlated with worse overall survival. High miR-126 expression was significantly associated with favorable prognosis only in patients with adenocarcinoma (p = 0.033). In multivariate analysis, miR-200c and tumor size remained as independent prognostic factors. Our results suggest that miR-126 might play tumor-suppressive and miR-200c an oncogenic role, and these miR's are potential prognostic biomarkers for NSCLC.
微小RNA(miRNA)是短链非编码RNA,通过转录后修饰对肿瘤发生产生关键影响,被认为是各种癌症诊断或预后的潜在生物标志物。尽管已有几种miRNA被提出作为非小细胞肺癌(NSCLC)的相关生物标志物,但这些miRNA的详细作用机制和已验证的预后意义仍存在争议。在本研究中,我们通过定量逆转录聚合酶链反应(qRT-PCR)评估了72例NSCLC和30例良性肺组织中miRNA-126(miR-126)和miR-200c的表达水平,并分析了miRNA表达与多种临床病理因素及患者生存的相关性。与良性对照组相比,NSCLC中miR-126表达显著下调(p < 0.001),而miR-200c表达在NSCLC中显著上调(p < 0.001)。肿瘤大小≤3 cm的NSCLC中miR-126表达显著高于肿瘤大小>3 cm的NSCLC(p = 0.026)。miRNA表达与临床病理特征之间无其他显著关联。在所有NSCLC患者的单因素生存分析中,高miR-200c表达(p = 0.037)、肿瘤体积大(p = 0.026)和淋巴管浸润(p = 0.012)与总体生存较差显著相关。仅在腺癌患者中,高miR-126表达与良好预后显著相关(p = 0.033)。在多因素分析中,miR-200c和肿瘤大小仍然是独立的预后因素。我们的结果表明,miR-126可能发挥肿瘤抑制作用,而miR-200c发挥致癌作用,并且这些miRNA是NSCLC潜在的预后生物标志物。