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通过数据挖掘在21种不同肿瘤类型的205个抗氧化基因中鉴定预后和预测生物标志物及可成药靶点。

Identification of Prognostic and Predictive Biomarkers and Druggable Targets among 205 Antioxidant Genes in 21 Different Tumor Types via Data-Mining.

作者信息

Özenver Nadire, Efferth Thomas

机构信息

Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.

Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey.

出版信息

Pharmaceutics. 2023 Jan 28;15(2):427. doi: 10.3390/pharmaceutics15020427.

Abstract

(1) Background: Oxidative stress is crucial in carcinogenesis and the response of tumors to treatment. Antioxidant genes are important determinants of resistance to chemotherapy and radiotherapy. We hypothesized that genes involved in the oxidative stress response may be valuable as prognostic biomarkers for the survival of cancer patients and as druggable targets. (2) Methods: We mined the KM Plotter and TCGA Timer2.0 Cistrome databases and investigated 205 antioxidant genes in 21 different tumor types within the context of this investigation. (3) Results: Of 4347 calculations with Kaplan-Meier statistics, 84 revealed statistically significant correlations between high gene expression and worse overall survival ( < 0.05; false discovery rate ≤ 5%). The tumor types for which antioxidant gene expression was most frequently correlated with worse overall survival were renal clear cell carcinoma, renal papillary cell carcinoma, and hepatocellular carcinoma. Seventeen genes were clearly overexpressed in tumors compared to their corresponding normal tissues ( < 0.001), possibly qualifying them as druggable targets (i.e., , , , , , , , , PRDX1, , , , , , , , and ). (4) Conclusions: We concluded that a sub-set of antioxidant genes might serve as prognostic biomarkers for overall survival and as druggable targets. Renal and liver tumors may be the most suitable entities for this approach.

摘要

(1) 背景:氧化应激在肿瘤发生及肿瘤对治疗的反应中起关键作用。抗氧化基因是化疗和放疗耐药性的重要决定因素。我们推测参与氧化应激反应的基因可能作为癌症患者生存的预后生物标志物以及可成药靶点具有重要价值。(2) 方法:我们挖掘了KM Plotter和TCGA Timer2.0顺式作用元件数据库,并在此研究背景下调查了21种不同肿瘤类型中的205个抗氧化基因。(3) 结果:在4347次Kaplan-Meier统计计算中,84次显示高基因表达与较差的总生存期之间存在统计学显著相关性(P<0.05;错误发现率≤5%)。抗氧化基因表达最常与较差总生存期相关的肿瘤类型是肾透明细胞癌、肾乳头状细胞癌和肝细胞癌。与相应正常组织相比,17个基因在肿瘤中明显过表达(P<0.001),这可能使它们有资格成为可成药靶点(即,,,,,,,,PRDX1,,,,,,,,和)。(4) 结论:我们得出结论,一部分抗氧化基因可能作为总生存期的预后生物标志物以及可成药靶点。肾脏和肝脏肿瘤可能是这种方法最适合的实体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ca7/9959161/e62563f32cce/pharmaceutics-15-00427-g001.jpg

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