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循环血清 miR-1249-3p、miR-3195 和 miR-3692-3p 在非小细胞肺癌中的差异表达。

Differential expression of circulating serum miR-1249-3p, miR-3195, and miR-3692-3p in non-small cell lung cancer.

机构信息

Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, 110029, India.

Department of Pulmonary Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India.

出版信息

Hum Cell. 2020 Jul;33(3):839-849. doi: 10.1007/s13577-020-00351-9. Epub 2020 Mar 25.

Abstract

Global deregulation in miRNA expression is a hallmark of cancer cell. An estimated 2300 mature miRNAs are encoded by human genome; role of many of which in carcinogenesis and as cancer biomarkers remains unexplored. In this study, we investigated the utility of miR-3692-3p, miR-3195, and miR-1249-3p as biomarkers in non-small cell lung cancer (NSCLC). For this prospective study, 115 subjects, including 75 NSCLC patients and 40 controls, were recruited. The expression of miR-3692-3p, miR-3195, and miR-1249-3p was checked using qRT-PCR. The miRNA expression was correlated with survival outcome and therapeutic response. There were no significant differences in the mean age of NSCLC patients and controls (56.2 and 55.3 years, respectively; p = 0.3242). Majority of NSCLC patients (67%) were smokers. We observed a significant upregulation of miR-3692-3p expression (p < 0.0001), while the expression of miR-3195 (p = 0.0017) and miR-1249-3p was significantly downregulated (p < 0.0001) in the serum of NSCLC patients as compared to controls. The expression of miR-1249-3p was significantly upregulated in lung adenocarcinoma versus lung squamous cell carcinoma (p = 0.0178). Interestingly, patients who responded to chemotherapy had higher expression of miR-1249-3p than non-responders (p = 0.0107). Moreover, patients with higher expression of miR-3195 had significantly longer overall survival (p = 0.0298). In multivariate analysis, miR-3195 emerged as independent prognostic factor for overall survival. We conclude that the miR-3195 may have prognostic significance, while miR-1249-3p may predict therapeutic response in NSCLC. Further studies are warranted to elucidate the role of these miRNAs in lung carcinogenesis and their utility as candidate cancer biomarkers.

摘要

全球 miRNA 表达的失调是非小细胞肺癌(NSCLC)的一个标志性特征。人类基因组中约有 2300 个成熟的 miRNA,其中许多在致癌作用和作为癌症生物标志物方面的作用仍未得到探索。在这项研究中,我们研究了 miR-3692-3p、miR-3195 和 miR-1249-3p 作为 NSCLC 生物标志物的效用。在这项前瞻性研究中,共招募了 115 名受试者,包括 75 名 NSCLC 患者和 40 名对照者。使用 qRT-PCR 检查 miR-3692-3p、miR-3195 和 miR-1249-3p 的表达。miRNA 表达与生存结果和治疗反应相关。NSCLC 患者和对照组的平均年龄(分别为 56.2 和 55.3 岁)没有显著差异(p=0.3242)。大多数 NSCLC 患者(67%)是吸烟者。我们观察到 miR-3692-3p 的表达显著上调(p<0.0001),而 miR-3195(p=0.0017)和 miR-1249-3p 的表达显著下调(p<0.0001)在 NSCLC 患者的血清中与对照组相比。miR-1249-3p 在肺腺癌与肺鳞癌中的表达显著上调(p=0.0178)。有趣的是,对化疗有反应的患者的 miR-1249-3p 表达高于无反应者(p=0.0107)。此外,miR-3195 表达较高的患者总生存时间明显延长(p=0.0298)。多变量分析显示,miR-3195 是总生存的独立预后因素。我们得出结论,miR-3195 可能具有预后意义,而 miR-1249-3p 可能预测 NSCLC 的治疗反应。需要进一步的研究来阐明这些 miRNA 在肺癌发生中的作用及其作为候选癌症生物标志物的应用。

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