结直肠癌SOS1、K-ras共表达对预后的影响  

Co-expression of SOS1 and k-ras in prediction of prognosis of colorectal cancer

作　　者：曹建 万相斌 杜记涛 赵卫杰 陈广龙 赵智力 董志闯 孙淼淼 李智 CAO Jian;WAN Xiang-bin;DU Ji-tao;ZHAO Wei-jie;CHEN Guang-long;ZHAO Zhi-li;DONG Zhi-chuang;SUN Miao-miao;LI Zhi(Department of General Surgery,The Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450000,Henan,China)

机构地区：[1]郑州大学附属肿瘤医院普外科,河南郑州450000 [2]郑州大学附属肿瘤医院病理科,河南郑州450000

出　　处：《广东医学》2019年第1期95-100,共6页Guangdong Medical Journal

基　　金：河南省科技攻关项目(编号:182102310127)

摘　　要：目的探讨在人结直肠癌组织中K-ras蛋白和SOS1蛋白的表达情况及其临床意义。方法选取术后病理确诊为结直肠癌的患者156例及相应癌旁> 5 cm结直肠黏膜组织标本45例,免疫组织化学(immunohistochemistry,IHC) S-P法检测K-ras蛋白和SOS1蛋白的表达,分析K-ras蛋白和SOS1蛋白阳性表达与结直肠癌患者临床病理学及预后的关系。结果 K-ras蛋白在结直肠癌细胞和癌旁肠黏膜细胞胞膜及胞质中表达,在结直肠癌组织中阳性率为78. 8%(123/156),癌旁组织中阳性率为53. 3%(24/45),差异有统计学意义(χ~2=11. 570,P=0. 001)。SOS1蛋白在结直肠癌细胞胞质和癌旁肠黏膜细胞胞质中表达,在结直肠癌组织中阳性率为50. 6%(79/156),在癌旁组织中阳性率为28. 9%(13/45),差异有统计学意义(χ~2=7. 174,P=0. 007)。K-ras蛋白阳性表达与患者性别(χ~2=4. 405,P=0. 036)、淋巴结转移(χ~2=9. 471,P=0. 002)及TNM分期(χ~2=6. 177,P=0. 013)有关,与年龄、肿瘤分化程度、肿瘤部位、浸润深度均无关(P>0. 05),SOS1蛋白阳性表达与结直肠癌临床病理无关(P> 0. 05)。K-ras和SOS1蛋白共表达的结直肠癌患者较K-ras阳性SOS1阴性的4年总生存期(overall survival,OS)短,差异有统计学意义(HR=2. 381,95%CI:1. 103～5. 137,P=0. 034 3),COX多因素分析显示:调整了性别、年龄、肿瘤分化程度、手术方式、是否行术后辅助化疗、肿瘤T分期、肿瘤N分期、免疫组化分组等因素后,提示肿瘤T分期(HR=2. 118,95%CI:1. 109～4. 046,P=0. 023)、肿瘤N分期(HR=2. 487,95%CI:1. 103～5. 610,P=0. 028)及免疫组化分组(HR=2. 795,95%CI:1. 272～6. 139,P=0. 010)是结直肠癌患者预后不良的独立危险因素。结论 K-ras蛋白可能与结直肠癌病情进展有关,K-ras蛋白和SOS1蛋白共阳性表达的结直肠癌患者的预后更差。Objective To investigate the expression and clinical significance of K-ras protein and SOS1 protein in human colorectal cancer tissues.Methods Specimens of 180 colorectal cancer tissues and 45 para-carcinoma tissues were collected from Henan Cancer Hospital.The expression of the K-ras and SOS1 proteins in both colorectal cancer and para-carcinoma tissues were assessed.Based on the results of immunohistochemistry,the correlation between the expression of K-ras and SOS and clinicopathological variables as well as prognosis were analyzed.Results K-ras protein was observed in the cell membrane and cytoplasm.There was a significant difference between the expression of K-ras protein in colorectal cancer tissues and para-carcinoma tissues( P = 0.001).The positive rate of K-ras in colorectal cancer tissues was 78.8%,and 53.3% in para-carcinoma tissues.SOS1 expression was only observed in the cytoplasm.The positive rate of SOS in colorectal cancer tissues was 50.6%,but 28.9% in para-carcinoma tissues.There was also a significant difference between the expression of SOS1 protein in colorectal cancer tissues and para-carcinoma tissues( P =0.007).Significant correlation of K-ras protein overexpression was observed with lymph node metastasis( P = 0.002)and TNM stage( P = 0.013).Whereas,no significant correlation was observed with age,differentiation,tumor site or invasion.There was no significant correlation between the expression of SOS1 protein and clinicopathological variables.The4 years overall survival( OS) of patients with positive K-ras and positive SOS1 was significantly shorter than that of positive K-ras and negative SOS1( HR = 2.381,95% CI: 1.103-5.137,P = 0.034).COX multivariate analysis showed that tumor T stage( HR = 2.118,95% CI: 1.109-4.046,P = 0.023),tumor N stage( HR = 2.487,95% CI: 1.103-5.610,P = 0.028) and immunohistochemical grouping( HR = 2.795,95% CI: 1.272-6.139,P = 0.010) were indepent risk factors of poor prognosis of patients with colorectal cancer.Conclusion K-ras protein may be involved in the pr

关 键 词：结直肠癌 K-ras蛋白 SOS1蛋白 预后 

分 类 号：R735.3[医药卫生—肿瘤]