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系统性鉴定与 11 种癌症类型铂类化疗反应相关的失调 lncRNAs。

Systematic identification of dysregulated lncRNAs associated with platinum-based chemotherapy response across 11 cancer types.

机构信息

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

出版信息

Genomics. 2020 Mar;112(2):1214-1222. doi: 10.1016/j.ygeno.2019.07.007. Epub 2019 Jul 11.

Abstract

Aberrant expression of long non-coding RNAs (lncRNAs) leads to the development of chemoresistance by regulating a series of biological processes, which is one of the major obstacles in the cancer treatment. This study aimed to identify some key lncRNAs that are associated with platinum-based chemoresistance in multiple cancers. Regulating the expression levels of these lncRNAs can enhance the sensitivity of patients to chemotherapy drugs and improve the therapeutic effect of cancer. By systematically analyzing 648 samples regarding platinum drug response from the Cancer Genome Atlas (TCGA), we have identified 32 dysregulated lncRNAs across 11 cancer types that could affect platinum-based chemotherapy response, of which 78.125% (25/32) were significantly down-regulated in drug-resistant samples. Drug response prediction model that had been constructed based on the expression pattern of these dysregulated lncRNAs could accurately predict the chemotherapy response of tumor patients, and the area under the curve (AUC) was between 0.8034 and 0.9984. In particular, all of these dysregulated lncRNAs that we identified were cancer-specific. They were significantly associated with the survival of tumor patients and could serve as cancer-specific biomarkers for prognosis. In conclusion, this study will contribute to improving the drug resistance of tumor patients during chemotherapy, and it is of real significance for selecting effective chemotherapy drugs and achieving precision medicine.

摘要

长链非编码 RNA(lncRNA)的异常表达通过调节一系列生物过程导致化疗耐药的发生,这是癌症治疗中的主要障碍之一。本研究旨在鉴定与多种癌症中基于铂的化疗耐药相关的一些关键 lncRNA。调节这些 lncRNA 的表达水平可以提高患者对化疗药物的敏感性,并改善癌症的治疗效果。通过系统分析癌症基因组图谱(TCGA)中 648 个关于铂类药物反应的样本,我们在 11 种癌症类型中鉴定出了 32 个失调的 lncRNA,它们可能影响基于铂的化疗反应,其中 78.125%(25/32)在耐药样本中显著下调。基于这些失调 lncRNA 的表达模式构建的药物反应预测模型可以准确预测肿瘤患者的化疗反应,曲线下面积(AUC)在 0.8034 到 0.9984 之间。特别是,我们鉴定的所有这些失调的 lncRNA 都是癌症特异性的。它们与肿瘤患者的生存显著相关,可作为预后的癌症特异性生物标志物。总之,本研究将有助于提高肿瘤患者在化疗过程中的耐药性,对于选择有效的化疗药物和实现精准医学具有重要意义。

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