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胃癌肿瘤突变负荷阈值变化分析

Analysis of Threshold Change of Tumor Mutation Burden in Gastric Cancer.

作者信息

He Xinwei, Yu Ming, Wang Xuezhong, Chen Jixian, Li Xianglin

机构信息

Department of General Surgery, Ruian People's Hospital, Wenzhou 325200, China.

Department of General Surgery, Ruian Hospital of Traditional Chinese Medicine, Wenzhou 325200, China.

出版信息

J Oncol. 2021 Jul 22;2021:3374939. doi: 10.1155/2021/3374939. eCollection 2021.

Abstract

BACKGROUND

The purpose of this study was to investigate the change of tumor mutation burden (TMB) in gastric cancer (GC) and its relationship with prognosis.

METHODS

A total of 262 patients with GC from January 2018 to December 2019 were included in this study. All patients were in the advanced stage and were treated with surgical removal of D2 lymph nodes and dissection. Clinical data and gene expression profile data of the GC dataset in The Cancer Genome Atlas were collected. Patients were randomly divided into a high-level group and a low-level group according to the TMB of 8 mutations/Mb. TMB of GC was calculated based on cell mutation data. Cox regression model was used to evaluate the relationship between TMB and prognosis of GC patients.

RESULTS

The total mutation rate of 262GC patients was 92.85%. The top 5 mutant genes were TP53, RB1, ARID1A, KMT2B, and RET. The expression level of TMB in GC patients was statistically significant with age, drinking history, and differentiation type. 94 of the 262 patients died, and 168 survived during the follow-up period. Patients with a high level of TMB had a worse prognosis than those with low level of TMB. The results of univariate and multivariate logistic analysis showed that the overall survival rate of GC patients was statistically significant with age, drinking history, clinical stage, differentiation type, and TMB.

CONCLUSION

GC patients are often accompanied by changes in TMB, and its expression level is closely related to the degree of pathological differentiation, which is an independent factor affecting the prognosis of GC patients. High TMB value can evaluate the prognosis and provide a reference for the formulation of clinical treatment plans for GC patients.

摘要

背景

本研究旨在探讨胃癌(GC)中肿瘤突变负荷(TMB)的变化及其与预后的关系。

方法

本研究纳入了2018年1月至2019年12月期间的262例GC患者。所有患者均处于晚期,接受了D2淋巴结清扫术。收集了癌症基因组图谱中GC数据集的临床数据和基因表达谱数据。根据8个突变/Mb的TMB将患者随机分为高水平组和低水平组。基于细胞突变数据计算GC的TMB。采用Cox回归模型评估TMB与GC患者预后的关系。

结果

262例GC患者的总突变率为92.85%。前5个突变基因是TP53、RB1、ARID1A、KMT2B和RET。GC患者的TMB表达水平在年龄、饮酒史和分化类型方面具有统计学意义。262例患者中有94例死亡,随访期间168例存活。TMB水平高的患者比TMB水平低的患者预后更差。单因素和多因素逻辑分析结果显示,GC患者的总生存率在年龄、饮酒史、临床分期、分化类型和TMB方面具有统计学意义。

结论

GC患者常伴有TMB变化,其表达水平与病理分化程度密切相关,是影响GC患者预后的独立因素。高TMB值可评估预后,为GC患者临床治疗方案的制定提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6218/8321718/d47bf0c41672/JO2021-3374939.001.jpg

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