微卫星不稳定性
癌症
结直肠癌
肺癌
危险系数
肿瘤科
免疫疗法
ARID1A型
比例危险模型
内科学
癌症研究
医学
生物
突变
基因
置信区间
遗传学
微卫星
等位基因
作者
Jung Yoon Choi,Kyong Hwa Park,Yeul Hong Kim,K. Jason,Ho Joong Sung,Yu-Wei Chen,Zhishan Chen,Chao Li,Wanqing Wen,Qingrun Zhang,Xiao‐Ou Shu,Zheng Wang,Jung Sun Kim,Xingyi Guo
标识
DOI:10.1158/1055-9965.epi-23-1466
摘要
Microsatellite instability (MSI) and tumor mutational burden (TMB) are predictive biomarkers for pan-cancer immunotherapy. The interrelationship between MSI-high (MSI-H) and TMB-high (TMB-H) in human cancers and their predictive value for immunotherapy in lung cancer remain unclear.We analyzed somatic mutation data from the Genomics Evidence Neoplasia Information Exchange (n = 46,320) to determine the relationship between MSI-H and TMB-H in human cancers using adjusted multivariate regression models. Patient survival was examined using the Cox proportional hazards model. The association between MSI and genetic mutations was assessed.Patients (31-89 %) with MSI-H had TMB-low phenotypes across 22 cancer types. Colorectal and stomach cancers showed the strongest association between TMB and MSI. TMB-H patients with lung cancer who received immunotherapy exhibited significantly higher overall survival (hazard ratio of 0.61, 95% confidence interval: 0.44-0.86) and progression-free survival (0.65, 0.47-0.91) compared to the TMB-low group; no significant benefit was observed in the MSI-H group. Patients with TMB and MSI phenotypes showed further improvement in overall and progression-free survival. We identified several mutated genes associated with MSI-H phenotypes, including known mismatch repair genes and novel mutated genes, such as ARID1A and ARID1B.Our results demonstrate that TMB-H and/or a combination of MSI-H can serve as biomarkers for immunotherapies in lung cancer.These findings suggest that distinct or combined biomarkers should be considered for immunotherapy in human cancers because notable discrepancies exist between MSI-H and TMB-H across different cancer types.
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