利用加权基因共表达网络分析鉴定与临床特征相关的 lncRNA 和 mRNA 生物标记物,将其作为卵巢癌个性化医疗的有用工具

IF 6 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
The EPMA journal Pub Date : 2019-07-19 eCollection Date: 2019-09-01 DOI:10.1007/s13167-019-00175-0
Na Li, Xianquan Zhan
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引用次数: 0

摘要

相关性:卵巢癌(OC)的发病机制和生物标志物在OC个性化医疗的诊断、有效治疗和预后评估方面仍不为人所知。目的:长非编码 RNA(lncRNA)通过多种机制与肿瘤发生相关。本研究旨在研究卵巢癌中癌症特异性的lncRNAs和mRNAs及其相关网络:本研究全面分析了癌症基因组图谱中OC组织中的lncRNAs和mRNAs及其相关的竞争内源性RNA(ceRNA)网络和lncRNA-RNA结合蛋白-mRNA网络,包括2562个癌症特异性lncRNAs(n = 352个OC组织)和5000个mRNAs(n = 359个OC组织)。利用加权基因共表达网络分析(WGCNA)构建共表达基因模块及其与临床特征的关系。在OC细胞中通过qRT-PCR证实了所发现的lncRNA和mRNA在统计学上的显著差异:结果:基于lncRNA的共表达模块与患者最初病理诊断时的年龄、淋巴侵袭、组织来源部位和血管侵袭显著相关,并鉴定出16个lncRNA(ACTA2-AS1、CARD8-AS1、HCP5、HHIP-AS1、HOTAIRM1、ITGB2-AS1、LINC00324、LINC00605、LINC01503、LINC01547、MIR31HG、MIR155HG、OTUD6B-AS1、PSMG3-AS1、SH3PXD2A-AS1和ZBED5-AS1)与OC患者的总生存率显著相关。基于mRNA的共表达模块与患者最初病理诊断时的年龄、淋巴侵袭、肿瘤残留病和血管侵袭显著相关,并发现了21个枢纽mRNA分子和11个mRNA(FBN3、TCF7L1、SBK1、TRO、TUBB2B、PLCG1、KIAA1549、PHC1、DNMT3A、LAMA1和C10orf82)与OC患者的总生存期密切相关。此外,还构建了五基因特征(OTUD6B-AS1、PSMG3-AS1、ZBED5-AS1、SBK1 和 PLCG1)预后模型来预测 OC 患者的风险评分。此外,starBase生物信息学还构建了OCs中的lncRNA-miRNA-mRNA和lncRNA-RNA结合蛋白-mRNA网络:这些新发现表明,OCs中的lncRNA相关网络是鉴定OCs生物标志物的有用资源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of clinical trait-related lncRNA and mRNA biomarkers with weighted gene co-expression network analysis as useful tool for personalized medicine in ovarian cancer.

Relevance: The pathogenesis and biomarkers of ovarian cancer (OC) remain not well-known in diagnosis, effective therapy, and prognostic assessment in OC personalized medicine. The novel identified lncRNA and mRNA biomarkers from gene co-expression modules associated with clinical traits provide new insight for effective treatment of ovarian cancer.

Purpose: Long non-coding RNAs (lncRNAs) are relevant to tumorigenesis via multiple mechanisms. This study aimed to investigate cancer-specific lncRNAs and mRNAs, and their related networks in OCs.

Methods: This study comprehensively analyzed lncRNAs and mRNAs with associated competing endogenous RNA (ceRNA) network and lncRNA-RNA binding protein-mRNA network in the OC tissues in the Cancer Genome Atlas, including 2562 cancer-specific lncRNAs (n = 352 OC tissues) and 5000 mRNAs (n = 359 OC tissues). The weighted gene co-expression network analysis (WGCNA) was used to construct the co-expression gene modules and their relationship with clinical traits. The statistically significant difference of identified lncRNAs and mRNAs was confirmed with qRT-PCR in OC cells.

Results: An lncRNA-based co-expression module was significantly correlated with patient age at initial pathologic diagnosis, lymphatic invasion, tissues source site, and vascular invasion, and identified 16 lncRNAs (ACTA2-AS1, CARD8-AS1, HCP5, HHIP-AS1, HOTAIRM1, ITGB2-AS1, LINC00324, LINC00605, LINC01503, LINC01547, MIR31HG, MIR155HG, OTUD6B-AS1, PSMG3-AS1, SH3PXD2A-AS1, and ZBED5-AS1) that were significantly related to overall survival in OC patients. An mRNA-based co-expression module was significantly correlated with patient age at initial pathologic diagnosis, lymphatic invasion, tumor residual disease, and vascular invasion; and identified 21 hub-mRNA molecules and 11 mRNAs (FBN3, TCF7L1, SBK1, TRO, TUBB2B, PLCG1, KIAA1549, PHC1, DNMT3A, LAMA1, and C10orf82) that were closely linked with OC patients' overall survival. Moreover, the prognostic model of five-gene signature (OTUD6B-AS1, PSMG3-AS1, ZBED5-AS1, SBK1, and PLCG1) was constructed to predict risk score in OC patients. Furthermore, starBase bioinformatics constructed the lncRNA-miRNA-mRNA and lncRNA-RNA binding protein-mRNA networks in OCs.

Conclusion: These new findings showed that lncRNA-related networks in OCs are a useful resource for identification of biomarkers in OCs.

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