肿瘤突变负荷与微卫星不稳定性在不同癌种中的分布模式研究  

Tumor Mutational Burden and Microsatellite Instabilityy Distribution in Different Cancer Types

作　　者：温阳 罗昕怡 陈豪 宋佳佳 周娟[1] 宋兴勃[1] Wen Yang;Luo Xinyi;Chen Hao;Song Jiajia;Zhou Juan;Song Xingbo(Department of Laboratory Medicine,West China Hospital,Sichuan University,Chengdu 610041,Sichuan,China)

机构地区：[1]四川大学华西医院实验医学科,成都610041

出　　处：《肿瘤预防与治疗》2025年第1期27-32,共6页Journal of Cancer Control And Treatment

基　　金：四川省自然科学基金(编号:2023NSFSC-0716)。

摘　　要：目的:肿瘤突变负荷(tumor mutational burden,TMB)与微卫星不稳定性(microsatellite instability,MSI)是免疫治疗的新兴肿瘤标志物。本研究旨在描绘不同类型肿瘤的TMB和MSI分布模式,为临床免疫治疗提供数据支撑。方法:纳入559例不同类型的肿瘤患者,收集肿瘤患者性别、年龄、肿瘤诊断、肿瘤TNM分期及病理分型等临床信息。利用Gene+Seq-2000测序仪对肿瘤组织进行1021个肿瘤相关基因的靶向测序,计算每个患者的TMB值并判读MSI状态。结果:研究结果显示,男性患者的TMB值显著高于女性患者(3.84 vs 2.88,P<0.001)。年龄>60岁患者TMB值高于年龄≤60岁患者(3.84 vs 2.88,P<0.001)。不同部位和TNM分期的肿瘤TMB值分布差异具有统计学意义(P<0.001)。相较于其他部位肿瘤,消化道肿瘤患者高TMB(tumor mutational burden-high,TMB-H)(35.07%)和微卫星高度不稳定(microsatellite instability-high,MSI-H)(9.70%)的占比均较高,其中结直肠癌最高(TMB-H占45.16%,MSI-H占12.90%)。肺鳞癌患者TMB-H比例显著高于腺癌(76.19%vs 11.28%,P<0.001)。此外,所有MSI-H患者均显示为TMB-H,且结直肠癌患者中同时存在TMB-H和MSI-H的比例最高。结论:男性患者的TMB值较高。消化道肿瘤患者的TMB-H和MSI-H比例高,肺鳞癌患者TMB-H比例高,是肿瘤免疫治疗中值得关注的指标。Objective:Tumor mutational burden(TMB)and microsatellite instability(MSI)are emerging tumor biomarkers for immunotherapy.This study aims to delineate the distribution of TMB and MSI across different tumor types,providing data supporting clinical immunotherapy.Methods:This study included 559 patients with various tumor types,and collected clinical information such as sex,age,diagnosis,TNM stage and pathological classification.Targeted sequencing of 1,021 tumor-related genes was performed using the Gene+Seq-2000 sequencer to calculate TMB values for patients and assess their MSI status.Results:The results of the study showed that male patients had significantly higher TMB values than female patients(3.84 us 2.88,P<0.001).Patients older than 60 years had higher TMB values than those younger or equal to 60 years(3.84 us 2.88,P<0.001).The differences in the distribution of TMB values by site and TNM stage were statistically significant(P<0.001).The proportions of high TMB(TMB-H)(35.07%)and high MSI(MSI-H)(9.70%)were significantly higher in gastrointestinal tumor patients than in patients with other tumor types,with the highest in colorectal cancer patients(45.16%for TMB-H,12.90%for MSI-H).The proportion of TMB-H was significantly higher in patients with lung squamous cell carcinoma than those with lung adenocarcinoma(76.19%us 11.28%,P<0.001).In addition,all MSI-H patients showed TMB-H,and colorectal cancer patients showed the highest proportions of both TMB-H and MSI-H.Conclusion:TMB values were higher in male patients.The high proportions of TMB-H and MSI-H in patients with digestive tract tumors and the high proportion of TMB-H in patients with lung squamous cell carcinoma are indicators of interest in tumor immunotherapy.

关 键 词：肿瘤突变负荷 微卫星稳定 恶性肿瘤 免疫治疗 分布情况 

分 类 号：R730.231[医药卫生—肿瘤]