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miR-19b 和 miR-146a 血清水平作为非小细胞肺癌的预后生物标志物。

Serum levels of miR-19b and miR-146a as prognostic biomarkers for non-small cell lung cancer.

机构信息

Department of Thoracic Surgery, the First Affiliated Hospital of Xiamen University.

出版信息

Tohoku J Exp Med. 2014 Feb;232(2):85-95. doi: 10.1620/tjem.232.85.

Abstract

MicroRNA (miRNA) is a type of small non-coding RNA molecule that has important roles in cancer initiation, promotion and progression by negatively regulating gene expression. In this study, we explored the role of miRNAs in the prognosis of patients with non-small cell lung cancer (NSCLC). The miRNA expression profiles were determined in 5 pairs of NSCLC and paracancerous tissues (3 adenocarcinomas and 2 squamous cell carcinomas). Aberrantly expressed miRNAs were validated by quantitative real-time PCR (qRT-PCR) in 61 pairs of NSCLC and paracancerous tissues. Differentially expressed miRNAs were further analyzed in sera from 94 healthy subjects and 94 advanced NSCLC patients receiving platinum-based chemotherapy. Three miRNAs (miR-19b, miR-146a, and miR-223) were significantly dysregulated in NSCLC tissues (P < 0.05). High miR-19b and low miR-146a expression in NSCLC tissues were associated with higher TNM stage, lymph node metastasis and poorer survival (P < 0.05). The serum levels of miR-19b in NSCLC patients were significantly higher (P < 0.001), whereas serum levels of miR-146a were significantly lower (P < 0.001), compared with those in controls. Serum levels of miR-19b and miR-146a were associated with overall survival of NSCLC patients (P < 0.05). Patients with low serum level of miR-19b and high serum level of miR-146a achieved a higher overall response rate and longer survival time (P < 0.05). These data suggest that miR-19b and miR-146a are potential biomarkers for the prediction of survival and response to chemotherapy in NSCLC.

摘要

微小 RNA(miRNA)是一种小的非编码 RNA 分子,通过负向调节基因表达,在癌症的起始、促进和进展中发挥重要作用。在本研究中,我们探讨了 miRNA 在非小细胞肺癌(NSCLC)患者预后中的作用。在 5 对 NSCLC 和癌旁组织(3 例腺癌和 2 例鳞状细胞癌)中确定了 miRNA 表达谱。通过定量实时 PCR(qRT-PCR)在 61 对 NSCLC 和癌旁组织中验证了异常表达的 miRNA。进一步在 94 例健康对照者和 94 例接受铂类化疗的晚期 NSCLC 患者的血清中分析差异表达的 miRNA。3 个 miRNA(miR-19b、miR-146a 和 miR-223)在 NSCLC 组织中明显失调(P<0.05)。NSCLC 组织中 miR-19b 高表达和 miR-146a 低表达与较高的 TNM 分期、淋巴结转移和较差的生存相关(P<0.05)。与对照组相比,NSCLC 患者血清中 miR-19b 水平显著升高(P<0.001),而 miR-146a 水平显著降低(P<0.001)。miR-19b 和 miR-146a 的血清水平与 NSCLC 患者的总生存期相关(P<0.05)。血清中 miR-19b 水平低、miR-146a 水平高的患者总反应率更高,生存时间更长(P<0.05)。这些数据表明,miR-19b 和 miR-146a 是预测 NSCLC 患者生存和化疗反应的潜在生物标志物。

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