血浆中循环MiR-1185、MiR-3183和MiR-584水平作为乳腺癌早期诊断的非侵入性生物标志物

Abolfazl Khalafi-Nezhad, Ahmad Abdollahi, Mahdi Barazesh, Marzieh Amani, Setare Motazedi, Vahid Ebrahimi, Ali Zarei
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摘要

简介:MicroRNAs (miRNAs)是一种短序列的非编码RNA分子,通过负调控基因表达,在不同的生物学通路中发挥主要的转录后基因调控作用,从而导致mRNA降解或翻译阻断。这些mirna的表达失调与包括乳腺癌在内的许多人类疾病的病因学相关。乳腺癌进展的各种细胞过程,包括细胞增殖、凋亡、转移、复发和化疗耐药,都是由致癌miRNA (oncomiR)调节的。目的:本研究的目的是研究循环microrna (miR-3183, miR-1185和miR-584)作为新型乳腺癌生物标志物的表达水平和潜在的诊断/预后作用。方法:本研究以99例20 ~ 63岁女性乳腺癌患者为病例组,50例年龄匹配的健康女性为对照组。从血清样品中提取microRNA后,采用real-time PCR对miR-1185、miR-3183a和miR-584进行相对表达定量。采用ROC曲线分析探讨mirna的诊断价值。结果:与对照组相比,女性BC病例中miRNA-1185、miRNA-584和miRNA-3183显著上调(p值<0.0001)。此外,通过对BC和HC的ROC分析,发现miRNA-584的AUC为0.844(95%置信区间(CI)),可作为乳腺癌筛查和随访的诊断性生物标志物。结论:基于血液样本的MiRNAs表达谱显示其在血清和血浆中的上调,并揭示了循环MiRNAs作为癌症诊断和筛查的新型无创生物标志物的巨大潜力。
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Circulating MiR-1185¸ MiR-3183, and MiR-584 Levels in Plasma as Diagnostic Non-invasive Biomarkers for Early Detection of Breast Cancer
Introduction: MicroRNAs (miRNAs) are non-coding RNA molecules with short sequences that function as main post-transcriptional gene regulators of different biological pathways via negative regulation of gene expression, thereby leading to either mRNA degradation or translational blockade. Dysregulated expression of these miRNAs has been related etiologically to many human diseases, including breast cancer. Various cellular processes of breast cancer progression, including cell proliferation, apoptosis, metastasis, recurrence and chemodrug resistance, are modulated by oncogenic miRNA (oncomiR). Objective: The objective of this investigation was to study the expression level and potential diagnostic/prognostic roles of circulating microRNAs (miR-3183, miR-1185, and miR-584) as novel breast cancer biomarkers. Method: The current study was conducted on 99 breast cancer (BC) female patients, aged between 20-63 years old, as the case group and 50 age-matched healthy females as control (HC). After microRNA extraction from the serum samples, real-time PCR was carried out for relative expression quantification of miR-1185, miR-3183a, and miR-584. The ROC curve analysis was performed to investigate the diagnostic value of miRNAs. Result: It was demonstrated that miRNA-1185, miRNA-584, and miRNA-3183 were significantly up-regulated (p-values <0.0001) in female BC cases compared to the control group. Besides, based on the ROC analysis for BC versus HC, it was revealed that the AUC for miRNA-584 was 0.844 (95% confidence interval (CI) and could be proposed as a diagnostic biomarker for breast cancer screening and follow-up. Conclusion: MiRNAs expression profiling using blood-based samples demonstrated their upregulation in the serum and plasma and revealed the concept that circulating miRNAs have high potential as novel noninvasive biomarkers for cancer diagnosis and screening.
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期刊介绍: Current Cancer Therapy Reviews publishes frontier reviews on all the latest advances in clinical oncology, cancer therapy and pharmacology. The journal"s aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians in cancer therapy.
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