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用于预测肝细胞癌预后、免疫特征和药物敏感性的三个E2F靶点相关基因特征

Three E2F target-related genes signature for predicting prognosis, immune features, and drug sensitivity in hepatocellular carcinoma.

作者信息

Zhang Baozhu, Chang Boyang, Wang Lu, Xu Yuzhong

机构信息

Department of Radiation Oncology, The People's Hospital of Baoan Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China.

Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

出版信息

Front Mol Biosci. 2023 Oct 3;10:1266515. doi: 10.3389/fmolb.2023.1266515. eCollection 2023.

Abstract

Hepatocellular carcinoma (HCC) is extremely malignant and difficult to treat. The adenoviral early region 2 binding factors (E2Fs) target pathway is thought to have a major role in tumor growth. This study aimed to identify a predictive E2F target signature and facilitate individualized treatment for HCC patients. We constructed an E2F target-related gene profile using univariate COX and LASSO regression models and proved its predictive efficacy in external cohorts. Furthermore, we characterized the role of the E2F target pathway in pathway enrichment, immune cell infiltration, and drug sensitivity of HCC. Lasso Cox regression created an E2F target-related gene signature of GHR, TRIP13, and CDCA8. HCC patients with high risk were correlated with shorter survival time, immune evasion, tumor stem cell characteristics and high sensitivity to Tipifarnib and Camptothecin drugs. Hepatocellular carcinoma prognosis was predicted by an E2F target signature. This finding establishes the theoretical usefulness of the E2F target route in customized identification and treatment for future research.

摘要

肝细胞癌(HCC)极具恶性且难以治疗。腺病毒早期区域2结合因子(E2Fs)靶向通路被认为在肿瘤生长中起主要作用。本研究旨在确定一个预测性的E2F靶点特征,并为HCC患者提供个体化治疗。我们使用单变量COX和LASSO回归模型构建了一个E2F靶点相关基因谱,并在外部队列中证明了其预测效力。此外,我们还阐述了E2F靶点通路在HCC的通路富集、免疫细胞浸润和药物敏感性中的作用。Lasso Cox回归创建了一个由生长激素受体(GHR)、TRIP13和细胞分裂周期相关蛋白8(CDCA8)组成的E2F靶点相关基因特征。高危HCC患者与较短的生存时间、免疫逃逸、肿瘤干细胞特征以及对替匹法尼和喜树碱药物的高敏感性相关。通过E2F靶点特征预测肝细胞癌预后。这一发现确立了E2F靶点通路在未来研究的定制识别和治疗中的理论实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1394/10579819/25e9f5869871/fmolb-10-1266515-g001.jpg

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