结直肠癌SOS1、K-ras共表达对预后的影响

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(χ2=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(χ2=7.174, P=0.007).K-ras蛋白阳性表达与患者性别(χ2=4.405, P=0.036)、淋巴结转移(χ2=9.471, P=0.002)及TNM分期(χ2=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 progression of colorectal cancer and patients, and both positive K-ras protein and SOS1 suggested a worse prognosis.