三阴性乳腺癌中差异表达 miRNA 的芯片分析:印度西部研究

IF 2 Q3 ONCOLOGY
Hemangini Vora , Nikita Bhatt , Dharvi Shah , Prabhudas Patel , Sonia Parikh , Priti Trivedi , Shashank Pandya
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引用次数: 0

摘要

背景三阴性乳腺癌(TNBC)是一种遗传学和形态学异质性癌症,具有侵袭性生物学行为和对治疗的特殊反应。它占所有乳腺癌的 15-20%,有两种亚型:基底样癌和非基底样癌。微RNA可调控基因表达,在TNBC中发挥着作用,有可能成为致癌基因或肿瘤抑制因子。结果 在 TNBC 中,共鉴定出 2410 个差异表达的 miRNA,其中 98% 的 miRNA 被下调,只有 2% 的 miRNA 被上调。观察到 55 个 miRNA 的上调,其靶向 16 个基因。发现的前 5 个基因是 CDNK1A、p53、TGFB1、APC 和 HRAS。在 7 种排序方法中,5 种排序方法确定 TGFB1 为最重要的枢纽基因。然后比较了病情缓解患者和病情复发患者的上调 miRNA 表达,结果发现只有 miR-4532 在病情复发患者中出现上调。此外,miR-4532的上调还显示出无病生存率和总生存率降低的趋势。下调的miRNA靶向238个参与TNBC发病和进展的基因。前五大枢纽基因是CDH1、PTEN、MYC、STAT3和VEGFA。在 7 种排序方法中,有 5 种排序方法认为 STAT3 是最重要的枢纽基因。这项研究发现了 32 个在 TNBC 中发挥肿瘤抑制作用并下调的新型 miRNA。其中,miR-1273g-3p 和 miR-4459 在所有 TNBC 患者中均有表达。这些 miRNA 下调的患者的无病生存率和总生存率明显下降。ROC曲线分析表明,miR-4532和miR-4459能成功地区分TNBC患者和健康对照组。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Microarray analysis of differentially expressed miRNA in triple negative breast cancer: A study of western India

Background

Triple-negative breast cancer (TNBC) is a genetically and morphologically heterogeneous group with aggressive biological behaviour and specific response to therapy. It accounts for 15–20% of all breast cancers and has two subtypes: basal like and non-basal like. MicroRNAs, which regulate gene expression, play a role in TNBC, potentially acting as oncogenes or tumor suppressors.

Objective

Identification of differentially expressed miRNA of potential clinical relevance in TNBC patients.

Methods

In this study, miRNA profiling by microarray was performed in tumor tissues of 86 patients with TNBC and 12 healthy individual. Further, the clinical relevance of differentially expressed miRNA was evaluated.

Results

In TNBC, 2410 differentially expressed miRNAs were identified and of them 98% were down-regulated, while only 2% were up-regulated. Up regulation of 55 miRNA was observed which target 16 genes. Top 5 genes identified were CDNK1A, p53, TGFB1, APC and HRAS. Of 7 ranking methods, 5 ranking method identified TGFB1 as most significant hub gene. Up regulated miRNA expression then compared between patients who undergone remission and patients who developed disease relapse and only miR-4532 was found upregulated in patients with disease relapse. Further, up regulation of miR-4532 showed a trend of reduced disease-free and overall survival. The down-regulated miRNAs target 238 genes involved in TNBC pathogenesis and progression. The top five hub genes were CDH1, PTEN, MYC, STAT3, and VEGFA. Of 7 ranking methods, 5 ranking method identified STAT3 as most significant hub gene. This study identified 32 novel miRNAs playing a tumor suppressive role and found down-regulated in TNBC. Among these two novel miRNAs, miR-1273g-3p and miR-4459 were found expressed in all TNBC patients. Patients with down-regulation of these miRNAs showed significantly reduced disease-free and overall survival. The ROC curve analysis indicated that miR-4532 and miR-4459 were successful in distinguishing TNBC patients from healthy controls.

Conclusion

Our data identified that up regulation of miR-4532 and down regulation of miR-4459 might have the potential to be used as both diagnostic and prognostic biomarker in TNBC.

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来源期刊
Advances in cancer biology - metastasis
Advances in cancer biology - metastasis Cancer Research, Oncology
CiteScore
2.40
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