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鉴定与人类 mRNA 结合的 SARS-CoV-2 蛋白作为一种新型标志物,预测肝细胞癌的总生存期。

Identification of SARS-CoV-2 Proteins Binding Human mRNAs As a Novel Signature Predicting Overall Survival in Hepatocellular Carcinoma.

机构信息

Department of Gastroenterology, Traditional Chinese Medicine Hospital of Taihe Country, Taihe, China.

出版信息

DNA Cell Biol. 2021 Feb;40(2):359-372. doi: 10.1089/dna.2020.6278. Epub 2020 Dec 4.

Abstract

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus causing coronavirus disease 2019 (COVID-19), has been confirmed in cancers through binding specific mRNAs to invade human cells. Therefore, the aim of this study described here was to develop and validate novel SARS-CoV-2 proteins binding human mRNAs () signature to predict overall survival (OS) in hepatocellular carcinoma (HCC). Using multivariate Cox regression analysis, a set of SPBRs was identified to establish a multigene signature in the Cancer Genome Atlas repositories cohort. Furthermore, a nomogram was established based on the signature and clinical risk factors to improve risk stratification for individual patients. External validation was performed in the International Cancer Genome Consortium (ICGC) cohort. A six-SPBR signature was built to classify patients into two risk groups using a risk score with different OS in two cohorts (all  < 0.0001). Multivariate regression analysis demonstrated the signature was an independent predictor of HCC. Moreover, the signature presented an excellent diagnostic power in differentiating HCC and normal tissues. Gene set enrichment analysis demonstrated that high-risk group was closely enriched in cell cycle, DNA replication, microRNAs in cancer, and cytokine-cytokine receptor interaction. The novel signature demonstrated great clinical value in predicting the OS for patients with HCC, and will provide a good reference between cancer research and SARS-CoV-2 and help individualized treatment in HCC.

摘要

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2),即导致 2019 年冠状病毒病(COVID-19)的病毒,已通过结合特定的 mRNA 入侵人类细胞而在癌症中得到证实。因此,本研究旨在开发和验证新型 SARS-CoV-2 蛋白与人类 mRNA 的结合物()特征,以预测肝细胞癌(HCC)的总体生存率(OS)。使用多变量 Cox 回归分析,从癌症基因组图谱(TCGA)数据库队列中确定了一组 SPBR,以建立多基因特征。此外,基于特征和临床危险因素建立了列线图,以改善个体患者的风险分层。在国际癌症基因组联合会(ICGC)队列中进行了外部验证。使用风险评分将具有不同 OS 的两个队列中的患者分为两个风险组(均<0.0001)构建了一个六基因 SPBR 特征。多变量回归分析表明该特征是 HCC 的独立预测因子。此外,该特征在区分 HCC 和正常组织方面具有出色的诊断能力。基因集富集分析表明,高危组与细胞周期、DNA 复制、癌症中的 microRNAs 和细胞因子-细胞因子受体相互作用密切相关。该新型特征在预测 HCC 患者的 OS 方面具有重要的临床价值,将为癌症研究与 SARS-CoV-2 之间提供良好的参考,并有助于 HCC 的个体化治疗。

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