结直肠癌SMAD4基因突变的临床意义  

Clinical Significance of SMAD4 Gene Mutation in Colorectal Cancer

作　　者：张海明 王伟杰[2] 张娜[3] 王文静 马世虎 苏进达 赵少辉 谢小亮[2] ZHANG Haiming;WANG Weijie;ZHANG Na;WANG Wenjing;MA Shihu;SU Jinda;ZHAO Shaohui;XIE Xiaoliang(Ningxia Medical University,Yinchuan 750004,China;Department of Colorectal Surgery,General Hospital of Ningxia Medical University,The First Clinical Medical College of Ningxia Medical University,Yinchuan 750004,China;Department of Obstetrics and Gynecology,Ningxia Hui Autonomous Region People’s Hospital,The Third Clinical Medical College of Ningxia Medical University,Yinchuan 750002,China)

机构地区：[1]宁夏医科大学,银川750004 [2]宁夏医科大学总医院结直肠外科,宁夏医科大学第一临床医学院,银川750004 [3]宁夏回族自治区人民医院妇产科,宁夏医科大学第三临床医学院,银川750002

出　　处：《宁夏医科大学学报》2025年第1期31-39,共9页Journal of Ningxia Medical University

基　　金：宁夏回族自治区重点研发计划项目(2023BEGO3038);宁夏自然科学基金项目(2024AAC03686)。

摘　　要：目的 探讨SMAD4基因突变与结直肠癌关键基因突变、临床病理特征的关系以及SMAD4蛋白在结直肠癌组织及癌旁组织表达的差异,分析其与结直肠癌发生和发展的关系及临床意义。方法 运用二代基因测序技术(NGS)检测310例结直肠癌组织中包括SMAD4基因在内的多种基因的突变情况。采用免疫组织化学技术分别检测SMAD4突变组和野生组的癌组织及癌旁组织的SMAD4蛋白表达水平。分别使用CD34、D2-40、S100标记结直肠癌组织的血管、淋巴管及神经组织,显微镜下观察肿瘤细胞浸润周围血管、淋巴管及神经情况。结果 310例结直肠癌组织中,50例结直肠癌发生SMAD4突变,突变率为16.1%,突变位点主要位于MH2结构域。SMAD4基因突变与患者的分化程度、淋巴结转移、远处转移、TNM分期、血管内皮生长因子(VEGF)表达水平相关(P均<0.05),与患者的年龄、性别、肿瘤大小、肿瘤位置、浸润深度、表皮生长因子(EGFR)表达及错配修复(MMR)等均无关(P均>0.05);SMAD4突变与KRAS、BRAF突变相关(P均<0.01),而与TP53、APC、PIK3CA、FBXW7、PTEN等基因突变不相关(P均>0.05)。SMAD4蛋白在突变组的表达低于野生组,且在癌组织的表达两组均低于癌旁组织(P均<0.05);在SMAD4突变组中,癌组织的SMAD4蛋白表达与患者的分化程度、淋巴结转移、TNM分期、血管浸润及淋巴管浸润均相关(P均<0.05);在SMAD4野生组中,癌组织的SMAD4蛋白表达与患者的年龄、性别、肿瘤大小、肿瘤位置、分化程度、浸润深度、淋巴结转移、远处转移、TNM分期、血管浸润、淋巴管浸润及神经浸润均不相关(P均>0.05)。结论 SMAD4基因突变伴随着SMAD4蛋白表达下降,促进肿瘤发生血管、淋巴管浸润,SMAD4基因可能成为结直肠癌精准治疗潜在的新靶点。Objective To explore the relationship between SMAD4 gene mutations and key gene mutations in colorectal cancer,clinical and pathological characteristics,as well as the differential expression of SMAD4 protein between colorectal cancer tissues and adjacent tissues and to analyze its relationship with the occurrence and development of colorectal cancer and its clinical significance.Methods The second-generation gene sequencing technology(NGS)was used to detect gene mutations,including the SMAD4 gene,in 310 cases of colorectal cancer tissues.Immunohistochemistry(IHC)was used to detect the expression levels of SMAD4 protein in cancer tissues and adjacent tissues of the SMAD4 mutation group and wild group,respectively.CD34,D2-40,S100 were respectively used to label the blood vessels,lymphatic vessels,and nerve tissues of colorectal cancer tissues,and the infiltration of tumor cells into surrounding blood vessels,lymphatic vessels,and nerves was observed under a microscope. Results Among 310 cases of colorectal cancer,50 cases had SMAD4 mutations,with a mutation rate of 16.1%. The mutation sites were mainly located in the MH_(2) domain. The SMAD4 gene mutation was closely related to the degree of differentiation,lymph node metastasis,distant metastasis,TNM staging,and vascular endothelial growth factor(VEGF) expression of patients,and the differences were statistically significant(P all<0.05). There was no significant correlation(P all>0.05)with the patient's age,gender,tumor size,tumor location,infiltration depth,epidermal growth factor receptor(EGFR) expression,and mismatch repair (MMR) status. The SMAD4 mutation was positively correlated with KRAS and BRAF mutations,and the differences were statistically significant(P all<0.01),while it was not correlated with gene mutations such as TP53,APC,PIK3CA,FBXW7,PTEN,and the differences were not statistically significant(P all>0.05). The expression of SMAD4 protein in the mutant group was significantly lower than that in the wild group,and the expression of both groups in c

关 键 词：结直肠癌 SMAD4基因 二代基因测序 血管浸润 淋巴管浸润 

分 类 号：R73[医药卫生—肿瘤]