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下一代测序揭示乳腺癌患者外泌体中差异表达的 microRNAs。

Differentially expressed microRNAs in exosomes of patients with breast cancer revealed by next‑generation sequencing.

机构信息

Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat‑sen University, Meizhou, Guangdong 514031, P.R. China.

Center for Cancer Prevention and Treatment, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat‑sen University, Meizhou, Guangdong 514031, P.R. China.

出版信息

Oncol Rep. 2020 Jan;43(1):240-250. doi: 10.3892/or.2019.7401. Epub 2019 Nov 6.

Abstract

MicroRNAs (miRNAs/miRs) in exosomes play crucial roles in the onset, progression and metastasis of cancer by regulating the stability of target mRNAs or by inhibiting translation. In the present study, differentially expressed miRNAs were identified in exosomes of 27 breast cancer patients and 3 healthy controls using RNA sequencing. The differentially expressed microRNAs were selected by bioinformatic analysis. Subjects were followed up for 2 years and exosomal miRNA profiles were compared between patients with and without recurrence of breast cancer. A total of 30 complementary DNA libraries were constructed and sequenced and 1,835 miRNAs were detected. There were no significant differences in the expression of miRNAs between the basal‑like, human epidermal growth factor receptor‑2+, luminal A, luminal B and healthy control (HC) groups. A total of 54 differentially expressed miRNAs were identified in triple‑negative breast cancer (TNBC) patients vs. HCs, including 20 upregulated and 34 downregulated miRNAs. The results of the reverse transcription‑quantitative PCR were consistent with this. Receiver operating characteristic curve analyses indicated that miR‑150‑5p [area under the curve (AUC)=0.705, upregulated], miR‑576‑3p (AUC=0.691, upregulated), miR‑4665‑5p (AUC=0.681, upregulated) were able to distinguish breast cancer patients with recurrence from those without recurrence. In conclusion, the present results indicated differences in miRNA expression profiles between patients with TNBC and healthy controls. Certain exosomal miRNAs were indicated to have promising predictive value as biomarkers for distinguishing breast cancer with recurrence from non‑recurrence, which may be utilized for preventive strategies.

摘要

外泌体中的 microRNAs(miRNAs/miRs)通过调节靶 mRNA 的稳定性或抑制翻译,在癌症的发生、进展和转移中发挥关键作用。本研究采用 RNA 测序技术,鉴定了 27 例乳腺癌患者和 3 例健康对照者外泌体中的差异表达 miRNAs。通过生物信息学分析选择差异表达的 microRNAs。对患者进行了 2 年的随访,并比较了乳腺癌复发患者和未复发患者的外泌体 miRNA 谱。构建并测序了 30 个 cDNA 文库,共检测到 1835 个 miRNAs。在基底样、人表皮生长因子受体 2+、管腔 A、管腔 B 和健康对照组之间,miRNAs 的表达没有显著差异。在三阴性乳腺癌(TNBC)患者与健康对照者中,共鉴定出 54 个差异表达的 miRNAs,包括 20 个上调和 34 个下调的 miRNAs。逆转录定量 PCR 的结果与这一结果一致。受试者工作特征曲线分析表明,miR-150-5p(AUC=0.705,上调)、miR-576-3p(AUC=0.691,上调)、miR-4665-5p(AUC=0.681,上调)能够区分有复发和无复发的乳腺癌患者。综上所述,本研究结果表明 TNBC 患者和健康对照者之间的 miRNA 表达谱存在差异。某些外泌体 miRNAs 具有作为区分有复发和无复发乳腺癌的生物标志物的潜在预测价值,可能用于预防策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88ad/6908931/b2d73f98a2aa/or-43-01-0240-g00.jpg

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