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基于癌症基因组图谱鉴定微小RNA作为乳腺癌的诊断生物标志物

Identification of MicroRNAs as Diagnostic Biomarkers for Breast Cancer Based on the Cancer Genome Atlas.

作者信息

Kim Jungho

机构信息

Department of Biomedical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea.

出版信息

Diagnostics (Basel). 2021 Jan 11;11(1):107. doi: 10.3390/diagnostics11010107.

DOI:10.3390/diagnostics11010107
PMID:33440868
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7827427/
Abstract

Breast cancer is the most common cancer among women worldwide. MicroRNAs (miRNAs or miRs) play an important role in tumorigenesis, and thus, they have been identified as potential targets for translational research with diagnostic, prognostic, and therapeutic markers. This study aimed to identify differentially expressed (DE) miRNAs in breast cancer using the Cancer Genome Atlas. The miRNA profiles of 755 breast cancer tissues and 86 adjacent non-cancerous breast tissues were analyzed using Multi Experiment Viewer; miRNA-mRNA network analyses and constructed KEGG pathways with the predicted target genes were performed. The clinical relevance of miRNAs was investigated using area under the receiver operating characteristic curve (AUC) analysis, sensitivity, and specificity. The analysis identified 28 DE miRNAs in breast cancer tissues, including nine upregulated and 19 downregulated miRNAs, compared to non-cancerous breast tissues ( < 0.001). The AUC for each DE miRNA, miR-10b, miR-21, miR-96, miR-99a, miR-100, miR-125b-1, miR-125b-2, miR-139, miR-141, miR-145, miR-182, miR-183, miR-195, miR-200a, miR-337, miR-429, and let-7c, exceeded 0.9, indicating excellent diagnostic performance in breast cancer. Moreover, 1381 potential target genes were predicted using the prediction database tool, miRNet. These genes are related to PD-L1 expression and PD-1 checkpoint in cancer, MAPK signaling, apoptosis, and TNF pathways; hence, they regulate the development, progression, and immune escape of cancer. Thus, these 28 miRNAs can serve as prospective biomarkers for the diagnosis of breast cancer. Taken together, these results provide insight into the pathogenic mechanisms and potential therapies for breast cancer.

摘要

乳腺癌是全球女性中最常见的癌症。微小RNA(miRNA或miR)在肿瘤发生过程中发挥着重要作用,因此,它们已被确定为转化研究中具有诊断、预后和治疗标志物作用的潜在靶点。本研究旨在利用癌症基因组图谱识别乳腺癌中差异表达(DE)的miRNA。使用多重实验查看器分析了755个乳腺癌组织和86个相邻非癌性乳腺组织的miRNA谱;进行了miRNA-mRNA网络分析,并使用预测的靶基因构建了KEGG通路。使用受试者工作特征曲线(AUC)分析、敏感性和特异性研究了miRNA的临床相关性。分析确定了乳腺癌组织中有28个DE miRNA,与非癌性乳腺组织相比,其中9个上调,19个下调(<0.001)。每个DE miRNA(miR-10b、miR-21、miR-96、miR-99a、miR-100、miR-125b-1、miR-125b-2、miR-139、miR-141、miR-145、miR-182、miR-183、miR-195、miR-200a、miR-337、miR-429和let-7c)的AUC超过0.9,表明在乳腺癌中具有出色的诊断性能。此外,使用预测数据库工具miRNet预测了1381个潜在靶基因。这些基因与癌症中的PD-L1表达和PD-1检查点、MAPK信号传导、细胞凋亡和TNF途径相关;因此,它们调节癌症的发生、发展和免疫逃逸。因此,这28个miRNA可作为乳腺癌诊断的前瞻性生物标志物。综上所述,这些结果为乳腺癌的致病机制和潜在治疗方法提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/d79e319c303a/diagnostics-11-00107-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/ddcd52ff166e/diagnostics-11-00107-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/a770dea7154c/diagnostics-11-00107-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/dd5c3021d933/diagnostics-11-00107-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/612c0d30884b/diagnostics-11-00107-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/7665ca0b727a/diagnostics-11-00107-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/d79e319c303a/diagnostics-11-00107-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/ddcd52ff166e/diagnostics-11-00107-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/92fee82eac5f/diagnostics-11-00107-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/a770dea7154c/diagnostics-11-00107-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/dd5c3021d933/diagnostics-11-00107-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/612c0d30884b/diagnostics-11-00107-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/7665ca0b727a/diagnostics-11-00107-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d6/7827427/d79e319c303a/diagnostics-11-00107-g007.jpg

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