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鉴定与 DNA 修复相关的五个基因特征,以预测食管癌患者的预后。

Identification of DNA-Repair-Related Five-Gene Signature to Predict Prognosis in Patients with Esophageal Cancer.

机构信息

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.

Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.

出版信息

Pathol Oncol Res. 2021 Mar 30;27:596899. doi: 10.3389/pore.2021.596899. eCollection 2021.

Abstract

Esophageal cancer (ESCA) is a leading cause of cancer-related mortality, with poor prognosis worldwide. DNA damage repair is one of the hallmarks of cancer. Loss of genomic integrity owing to inactivation of DNA repair genes can increase the risk of cancer progression and lead to poor prognosis. We aimed to identify a novel gene signature related to DNA repair to predict the prognosis of ESCA patients. Based on gene expression profiles of ESCA patients from The Cancer Genome Atlas and gene set enrichment analysis, 102 genes related to DNA repair were identified as candidates. After stepwise Cox regression analysis, we established a five-gene prognostic model comprising DGCR8, POM121, TAF9, UPF3B, and BCAP31. Kaplan-Meier survival analysis confirmed a strong correlation between the prognostic model and survival. Moreover, we verified the clinical value of the prognostic signature under the influence of different clinical parameters. We found that small-molecule drugs (trametinib, selumetinib, and refametinib) could help to improve patient survival. In summary, our study provides a novel and promising prognostic signature based on DNA-repair-related genes to predict survival of patients with ESCA. Systematic data mining provides a theoretical basis for further exploring the molecular pathogenesis of ESCA and identifying therapeutic targets.

摘要

食管癌(ESCA)是全球癌症相关死亡率的主要原因,预后较差。DNA 损伤修复是癌症的标志之一。由于 DNA 修复基因失活导致基因组完整性丧失,会增加癌症进展的风险,并导致预后不良。我们旨在确定与 DNA 修复相关的新型基因特征,以预测 ESCA 患者的预后。基于来自癌症基因组图谱的 ESCA 患者的基因表达谱和基因集富集分析,确定了 102 个与 DNA 修复相关的候选基因。经过逐步 Cox 回归分析,我们建立了一个由 DGCR8、POM121、TAF9、UPF3B 和 BCAP31 组成的五基因预后模型。Kaplan-Meier 生存分析证实了该预后模型与生存之间的强相关性。此外,我们还验证了该预后特征在不同临床参数影响下的临床价值。我们发现小分子药物(曲美替尼、塞尔美替尼和来法替尼)可以帮助改善患者的生存。总之,我们的研究提供了一个基于 DNA 修复相关基因的新型且有前途的预后特征,可用于预测 ESCA 患者的生存情况。系统的数据挖掘为进一步探索 ESCA 的分子发病机制和确定治疗靶点提供了理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f0f/8262199/4caffe0f8d3f/pore-27-596899-g001.jpg

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