微卫星不稳定性结直肠癌14239例患者的分子特征

Molecular characteristics of 14239 patients with microsatellite instability colorectal cancer

目的对四川地区结直肠癌患者进行基因测序,以分析其微卫星不稳定(MSI)的分子特征。方法采用第二代测序技术(NGS)方法对2017年至2022年四川省成都市第三人民医院14239例结直肠癌患者的进行检测,包含单核苷酸位点变异(SNV)、插入和缺失(InDel)、拷贝数变异(CNV)、基因融合(fusion)、MSI、肿瘤突变负荷(TMB)、EB病毒(EBV)等。比较高度微卫星不稳定(MSI-H)患者(MSI-H组,n=1018)和微卫星稳定(MSS)患者(MSS组,n=13221)的临床及分子特征。结果MSI在结直肠癌中的发生率为7.15%,且MSI检出率在诊断年龄、肿瘤位置、样本类型等方面均存在差异。MSI-H组TMB显著高于MSS组(92.8突变/Mb vs 12.7突变/Mb,P<0.05)。结直肠癌患者EBV阳性率为0.43%(27例),而MSI-H未检测到有EBV阳性的患者。ERBB 2、PIK3CA和BRAF等在MSI-H组中的频率都明显更高,但APC(51.26%vs 70.76%,χ^(2)=168.823,P<0.01)、TP53(27.76%vs 69.54%,χ^(2)=739.882,P<0.01)、NRAS(1.86%vs 3.98%,χ^(2)=11.445,P<0.01)在MSS组中的阳性率更高。此外,携带一个DNA错配修复基因(MMR)变异的患者在MSI-H型中占比更高(P<0.05)。结论四川地区结直肠癌MSI-H型与MSS型具有不同的分子特征,且在TMB及EBV感染也有所差异。

Objective To analyze their molecular characteristics of microsatellite instability(MSI)by sequencing colorectal cancer patients in Sichuan region.Methods Next generation sequencing(NGS)was used to test 14239 colon cancer patients from 2017 to 2022 in the Third People s Hospital of Chengdu for single nucleotide variation(SNV),insertion-deletion(InDel),copy number variation(CNV),fusion,MSI,tumor mutational burden(TMB),and Epstein-Barr virus(EBV).The clinical and molecular characteristics of highly microsatellite unstable(MSI-H)patients(MSI-H group,n=1018)and microsatellite stable(MSS)patients(MSS group,n=13221)were compared.Results The incidence rate of MSI in colorectal cancer was 7.15%,and detection rate of MSI varied in terms of age at diagnosis,tumour location and sample type.TMB was significantly higher in patients with MSI-H than in patients with microsatellite stable(MSS)(92.8 mutations/Mb vs 12.7 mutations/Mb,P<0.05).EBV positivity in patients with colorectal cancer was 0.43%,but no patient with positive EBV was found in MSI-H.ERBB2,PIK3CA and BRAF all had significantly higher mutation frequencies in the MSI-H group,however,the positive rates of APC(51.26%vs 70.76%,χ^(2)=168.823,P<0.01),TP53(27.76%vs 69.54%,χ^(2)=739.882,P<0.01)and NRAS(1.86%vs 3.98%,χ^(2)=11.445,P<0.01)were higher in the MSS group.Furthermore,MSI-H patients had a higher proportion of carrying a mismatch repair(MMR)gene variant(P<0.05).Conclusion MSI-H and MSS types of colorectal cancer in Sichuan have different molecular characteristics and differ in TMB and EBV infections.