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食管腺癌患者中突变与肿瘤突变负荷、预后及抗肿瘤免疫的关联

Association of Mutation With Tumor Mutation Burden, Prognosis, and Antitumor Immunity in Patients With Esophageal Adenocarcinoma.

作者信息

Liu Zaoqu, Liu Long, Jiao Dechao, Guo Chunguang, Wang Libo, Li Zhaonan, Sun Zhenqiang, Zhao Yanan, Han Xinwei

机构信息

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Interventional Institute of Zhengzhou University, Zhengzhou, China.

出版信息

Front Genet. 2021 May 17;12:669694. doi: 10.3389/fgene.2021.669694. eCollection 2021.

Abstract

: Esophageal adenocarcinoma (EAC) remains a leading cause of cancer-related deaths worldwide and demonstrates a predominant rising incidence in Western countries. Recently, immunotherapy has dramatically changed the landscape of treatment for many advanced cancers, with the benefit in EAC thus far been limited to a small fraction of patients. : Using somatic mutation data of The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium, we delineated the somatic mutation landscape of EAC patients from US and England. Based on the expression data of TCGA cohort, multiple bioinformatics algorithms were utilized to perform function annotation, immune cell infiltration analysis, and immunotherapy response assessment. : We found that was a common frequently mutated gene in both cohorts, and patients with mutation suggested higher tumor mutation burden (TMB), better prognosis, and superior expression of immune checkpoints. Moreover, mutation upregulated the signaling pathways implicated in immune response and enhanced antitumor immunity in EAC. Multiple bioinformatics algorithms for assessing immunotherapy response demonstrated that patients with mutation might benefit more from immunotherapy. In order to provide additional reference for antitumor therapy of different status, we identified nine latent antitumor drugs associated with status in EAC. : This study reveals a novel gene whose mutation could be served as a potential biomarker for prognosis, TMB, and immunotherapy of EAC patients.

摘要

食管腺癌(EAC)仍然是全球癌症相关死亡的主要原因,并且在西方国家呈现出显著上升的发病率。最近,免疫疗法极大地改变了许多晚期癌症的治疗格局,然而迄今为止,其在EAC中的益处仅限于一小部分患者。

利用癌症基因组图谱(TCGA)和国际癌症基因组联盟的体细胞突变数据,我们描绘了来自美国和英国的EAC患者的体细胞突变图谱。基于TCGA队列的表达数据,运用多种生物信息学算法进行功能注释、免疫细胞浸润分析和免疫治疗反应评估。

我们发现, 是两个队列中常见的频繁突变基因,携带 突变的患者显示出更高的肿瘤突变负荷(TMB)、更好的预后以及免疫检查点的高表达。此外, 突变上调了与免疫反应相关的信号通路,并增强了EAC中的抗肿瘤免疫力。多种评估免疫治疗反应的生物信息学算法表明,携带 突变的患者可能从免疫治疗中获益更多。为了为不同 状态的抗肿瘤治疗提供额外参考,我们在EAC中鉴定了九种与 状态相关的潜在抗肿瘤药物。

这项研究揭示了一个新基因,其突变可作为EAC患者预后、TMB和免疫治疗的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7e1/8166246/c6476f2979e5/fgene-12-669694-g001.jpg

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