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基于加权基因共表达网络分析的新型乳腺癌干性指数相关长链非编码RNA特征的开发与验证

Development and Validation of a Novel Stemness-Index-Related Long Noncoding RNA Signature for Breast Cancer Based on Weighted Gene Co-Expression Network Analysis.

作者信息

Qian Da, Qian Cheng, Ye Buyun, Xu Ming, Wu Danping, Li Jialu, Li Dong, Yu Bin, Tao Yijing

机构信息

Department of Burn and Plastic Surgery-Hand Surgery, Changshu Hospital Affiliated to Soochow University, Changshu, China.

School of Computer Science and Engineering, Changshu Institute of Technology, Changshu, China.

出版信息

Front Genet. 2022 Feb 22;13:760514. doi: 10.3389/fgene.2022.760514. eCollection 2022.

Abstract

Breast cancer (BC) is a major leading cause of woman deaths worldwide. Increasing evidence has revealed that stemness features are related to the prognosis and progression of tumors. Nevertheless, the roles of stemness-index-related long noncoding RNAs (lncRNAs) in BC remain unclear. Differentially expressed stemness-index-related lncRNAs between BC and normal samples in The Cancer Genome Atlas database were screened based on weighted gene co-expression network analysis and differential analysis. Univariate Cox and least absolute shrinkage and selection operator regression analyses were performed to identify prognostic lncRNAs and construct a stemness-index-related lncRNA signature. Time-dependent receiver operating characteristic curves were plotted to evaluate the predictive capability of the stemness-index-related lncRNA signature. Moreover, correlation analysis and functional enrichment analyses were conducted to investigate the stemness-index-related lncRNA signature-related biological function. Finally, a quantitative real-time polymerase chain reaction was used to detect the expression levels of lncRNAs. A total of 73 differentially expressed stemness-index-related lncRNAs were identified. Next, FAM83H-AS1, HID1-AS1, HOXB-AS1, RP11-1070N10.3, RP11-1100L3.8, and RP11-696F12.1 were used to construct a stemness-index-related lncRNA signature, and receiver operating characteristic curves indicated that stemness-index-related lncRNA signature could predict the prognosis of BC well. Moreover, functional enrichment analysis suggested that differentially expressed genes between the high-risk group and low-risk group were mainly involved in immune-related biological processes and pathways. Furthermore, functional enrichment analysis of lncRNA-related protein-coding genes revealed that FAM83H-AS1, HID1-AS1, HOXB-AS1, RP11-1070N10.3, RP11-1100L3.8, and RP11-696F12.1 were associated with neuroactive ligand-receptor interaction, AMPK signaling pathway, PPAR signaling pathway, and cGMP-PKG signaling pathway. Finally, quantitative real-time polymerase chain reaction revealed that FAM83H-AS1, HID1-AS1, RP11-1100L3.8, and RP11-696F12.1 might be used as the potential diagnostic biomarkers of BC. The stemness-index-related lncRNA signature based on FAM83H-AS1, HID1-AS1, HOXB-AS1, RP11-1070N10.3, RP11-1100L3.8, and RP11-696F12.1 could be used as an independent predictor for the survival of BC, and FAM83H-AS1, HID1-AS1, RP11-1100L3.8, and RP11-696F12.1 might be used as the diagnostic markers of BC.

摘要

乳腺癌(BC)是全球女性死亡的主要原因之一。越来越多的证据表明,干性特征与肿瘤的预后和进展有关。然而,与干性指数相关的长链非编码RNA(lncRNAs)在乳腺癌中的作用仍不清楚。基于加权基因共表达网络分析和差异分析,在癌症基因组图谱数据库中筛选了乳腺癌与正常样本之间差异表达的与干性指数相关的lncRNAs。进行单因素Cox分析以及最小绝对收缩和选择算子回归分析,以鉴定预后lncRNAs并构建与干性指数相关的lncRNA特征。绘制时间依赖性受试者工作特征曲线,以评估与干性指数相关的lncRNA特征的预测能力。此外,进行相关性分析和功能富集分析,以研究与干性指数相关的lncRNA特征相关的生物学功能。最后,使用定量实时聚合酶链反应检测lncRNAs的表达水平。共鉴定出73个差异表达的与干性指数相关的lncRNAs。接下来,使用FAM83H-AS1、HID1-AS1、HOXB-AS1、RP11-1070N10.3、RP11-1100L3.8和RP11-696F12.1构建与干性指数相关的lncRNA特征,受试者工作特征曲线表明,与干性指数相关的lncRNA特征可以很好地预测乳腺癌的预后。此外,功能富集分析表明,高危组和低危组之间的差异表达基因主要参与免疫相关的生物学过程和通路。此外,对lncRNA相关蛋白质编码基因的功能富集分析表明,FAM83H-AS1、HID1-AS1、HOXB-AS1、RP11-1070N10.3、RP11-1100L3.8和RP11-696F12.1与神经活性配体-受体相互作用、AMPK信号通路、PPAR信号通路和cGMP-PKG信号通路有关。最后,定量实时聚合酶链反应表明,FAM83H-AS1、HID1-AS1、RP11-1100L3.8和RP11-696F12.1可能用作乳腺癌的潜在诊断生物标志物。基于FAM83H-AS1、HID1-AS1、HOXB-AS1、RP11-1070N10.3、RP11-1100L3.8和RP11-696F12.1的与干性指数相关的lncRNA特征可作为乳腺癌生存的独立预测指标,FAM83H-AS1、HID1-AS1、RP11-1100L3.8和RP11-696F12.1可能用作乳腺癌的诊断标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01a0/8902307/9062bf63d4bd/fgene-13-760514-g001.jpg

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