摘要
目的 探讨结直肠癌(CRC)的微卫星不稳定(MSI)状态与KRAS、NRAS、BRAF基因突变、临床病理特征及预后的相关性。方法 选取2015年3月至2020年12月于汕头市中心医院和中山大学肿瘤防治中心收治的经病理确诊为CRC的861例患者作为研究对象,检测其4种错配修复(MMR)蛋白表达、MSI状态,KRAS、NRAS、NRAS基因突变情况。分析MMR蛋白表达、KRAS、NRAS和BRAF基因突变与CRC患者临床病理特征的相关性,MMR蛋白表达与KRAS、NRAS和BRAF基因突变的相关性,并采用COX回归模型探讨CRC患者2年内死亡的独立影响因素。结果 CRC中的MMR蛋白表达总缺失率为12.08%,KRAS基因突变率为42.28%,NRAS基因突变率为2.21%,BRAF基因突变率为6.50%。不同年龄、肿瘤部位、组织学类型、肿瘤最大径、分化程度、TNM分期、淋巴结转移状态、CEA水平的患者MMR蛋白表达比较,差异有统计学意义(P<0.05)。不同性别、肿瘤部位、组织学类型、分化程度、TNM分期、淋巴结转移状态、CA199水平的患者KRAS基因突变比较,差异有统计学意义(P<0.05)。不同CEA水平的患者NRAS基因突变比较,差异有统计学意义(P<0.05)。不同肿瘤部位、组织学类型、肿瘤最大径、分化程度、TNM分期、淋巴结转移状态的患者BRAF基因突变比较,差异有统计学意义(P<0.05)。MMR蛋白表达与KRAS基因突变呈负相关(r=-0.137,P<0.001)。MMR蛋白表达与NRAS基因突变不相关(r=-0.007,P=0.834)。MMR蛋白表达与BRAF基因突变呈正相关(r=0.162,P<0.001)。淋巴结转移、KRAS突变、BRAF突变、MSI-H是CRC患者2年内死亡的独立影响因素。结论 MSI状态、KRAS、NRAS、BRAF基因突变与CRC的临床病理特征具有相关性,上述指标的检测有助于CRC的生物学行为分析及预后判断。
Objective To explore the relationship between microsatellite instability(MSI)status and KRAS,NRAS,BRAF gene mutations,clinicopathologic features and prognosis in colorectal cancer(CRC).Methods A total of 861 patients diagnosed with CRC by pathology admitted to Shantou Central Hospital and Sun Yat-sen University Cancer Center from March 2015 to December 2020 were selected as the study objects to detect the expression of 4 mismatch repair(MMR)proteins,MSI status,and gene mutations of KRAS,NRAS,and NRAS.The correlation between MMR protein expression,KRAS,NRAS and BRAF gene mutations and clinicopathological features of CRC patients was analyzed,and the correlation between MMR protein expression and KRAS,NRAS and BRAF gene mutations were analyzed.The independent influencing factors of mortality in CRC patients within two years were analyzed by COX regression model.Results The total deletion rate of MMR protein expression in CRC was 12.08%,the mutation rate of KRAS gene was 42.28%,the mutation rate of NRAS gene was 2.21%,and the mutation rate of BRAF gene was 6.50%.There were significant differences in MMR protein expression among patients with different age,tumor site,histological type,tumor maximum diameter,differentiation degree,TNM stage,lymph node metastasis status and CEA level(P<0.05).There were significant differences in KRAS gene mutation among patients with different sex,tumor site,histological type,differentiation degree,TNM stage,lymph node metastasis status and CA199 level(P<0.05).The difference of NRAS gene mutation in patients with different CEA levels was statistically significant(P<0.05).There were significant differences in BRAF gene mutation among patients with different tumor sites,histological types,tumor maximum diameter,differentiation degree,TNM stage and lymph node metastasis status(P<0.05).MMR protein expression was negatively correlated with KRAS gene mutation(r=-0.137,P<0.001).There was no correlation between MMR protein expression and NRAS gene mutation(r=-0.007,P=0.834).The expression of M
作者
赵勇强
王媛媛
刘春鹏
詹晓芬
魏巍然
古家美
ZHAO Yongqiang;WANG Yuanyuan;LIU Chunpeng;ZHAN Xiaofen;WEI Weiran;GU Jiamei(Department of Pathology,Shantou Central Hospital,Shantou,Guangdong 515031,China;Department of Molecular Diagnosis,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong 510060,China)
出处
《国际检验医学杂志》
CAS
2024年第8期969-975,共7页
International Journal of Laboratory Medicine
基金
汕头市科技计划医疗卫生类别项目(汕府科[2020]5号-39)。
