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构建和分析胰腺癌铁死亡相关基因预后特征。

The construction and analysis of a ferroptosis-related gene prognostic signature for pancreatic cancer.

机构信息

Department of Gastroenterology, Fudan University Jinshan Hospital, Shanghai, China.

Department of Pancreatic Surgery, Fudan University Huashan Hospital, Shanghai, China.

出版信息

Aging (Albany NY). 2021 Apr 4;13(7):10396-10414. doi: 10.18632/aging.202801.

Abstract

Ferroptosis is a regulated cell death nexus linking metabolism, redox biology and diseases including cancer. The aim of the present study was to identify a ferroptosis-related gene prognostic signature for pancreatic cancer (PCa) by systematic analysis of transcriptional profiles from Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Altogether 14 ferroptosis-relevant genes with potential prognostic values were identified, based on which a risk score formula was constructed. According to the risk scores, we classified the patients into a high- and a low-risk score group. It was verified in Gene Expression Omnibus (GEO) and ICGC (International Cancer Genome Consortium) datasets. The Kaplan-Meier survival curves demonstrated that patients with lower risk scores had significantly favorable overall survival (OS) (P < 0.0001). The area under the receiver operating curve (ROC) for 12, 18 and 24 months was about 0.8 in all patients. The result of immune status analysis revealed that the signature significantly associated with the immune infiltration and immune checkpoint blockade (ICB) proteins. In addition, we used quantitative real time PCR (q-rtPCR) and Human Protein Atlas (HPA) to validate the expression of the key genes. Collectively, the signature is valuable for survival prediction of PCa patients. As the signature also has relevance with the immune characteristics, it may help improve the efficacy of personalized immunotherapy.

摘要

铁死亡是一种代谢、氧化还原生物学与癌症等疾病相关的调控性细胞死亡枢纽。本研究的目的是通过对癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)转录谱的系统分析,鉴定胰腺癌(PCa)的铁死亡相关基因预后特征。基于具有潜在预后价值的 14 个铁死亡相关基因,构建了风险评分公式。根据风险评分,我们将患者分为高风险评分组和低风险评分组。在基因表达综合数据库(GEO)和国际癌症基因组联盟(ICGC)数据集得到了验证。Kaplan-Meier 生存曲线表明,风险评分较低的患者总生存期(OS)显著延长(P<0.0001)。在所有患者中,12、18 和 24 个月的受试者工作特征曲线(ROC)下面积约为 0.8。免疫状态分析的结果表明,该特征与免疫浸润和免疫检查点阻断(ICB)蛋白显著相关。此外,我们使用实时荧光定量 PCR(q-rtPCR)和人类蛋白质图谱(HPA)验证了关键基因的表达。综上所述,该特征可用于预测 PCa 患者的生存情况。由于该特征与免疫特征相关,它可能有助于提高个性化免疫治疗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/670e/8064155/477a9042ec50/aging-13-202801-g001.jpg

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