自噬相关蛋白LC3Ⅱ与结直肠癌血管生成和转移的相关性研究

Correlation between autophagy-associated protein LC3Ⅱ and vascular formation and metastasis of colorectal cancer

目的:探讨自噬相关蛋白LC3Ⅱ与结直肠癌血管生成和转移的相关性。方法:采用免疫组化方法检测结直肠癌(90例)、结直肠腺瘤(20例)、癌旁组织(20例)及转移灶(60例)中LC3Ⅱ、VEGF及CD 34的表达,分析在结直肠癌发生发展及临床病理学特征中LC3Ⅱ和VEGF的表达水平及微血管密度(MVD)分布情况,采用Spearman法分析结直肠癌中LC3Ⅱ表达与VEGF及MVD的相关性。结果:结直肠癌中LC3Ⅱ及VEGF的表达及MVD较癌旁组织及腺瘤组织明显增加(P=0.000、0.000、P=0.000),但癌旁组织及腺瘤组织的均相近(P均>0.05)。LC3Ⅱ及VEGF的表达和MVD与结直肠癌组织学分化、伴淋巴结转移、癌结节、伴肝转移、临床分期相关(LC3Ⅱ:P=0.015、0.018、0.008、0.034、0.008;VEGF:P=0.034、0.043、0.006、0.009、0.002;MVD:P=0.039、0.002、0.026、0.034、0.004),与患者年龄、性别、肿瘤大小和浸润深度无关(P均>0.05)。LC3Ⅱ、VEGF的表达及MVD在淋巴结转移灶、癌结节及肝转移灶中均相近(P均>0.05),但与原发灶不同义(分别为LC3Ⅱ:P=0.037、0.036、0.037;VEGF:P=0.041、0.011、0.041;MVD:P=0.020、0.039、0.020)。相关性分析发现结直肠癌中LC3Ⅱ的表达与VEGF的表达及MVD呈正相关关系(分别为r=0.520,P=0.000;r=0.656,P=0.000)。结论:抑制自噬可能是改善经抗血管治疗结直肠癌患者预后的一种辅助方法。

Objective To investigate the relationship between autophagy-associated protein LC3Ⅱand angiogenesis and metastasis of colorectal cancer.Methods The expression of LC3Ⅱ,vascular endothelial growth factor(VEGF)and CD34 in colorectal cancer(n=90),colorectal adenocarcinoma(n=20),cancer-adjacent tissues(n=20)and metastatic lesions(n=60)was detected by immunohistochemistry,to analyze the expression level of LC3Ⅱand vascular growth factor and the distribution of microvascular density(MVD)in colorectal cancer development and clinical pathological features,and to analyze the correlation between LC3Ⅱexpression and vascular growth factor and MVD in colorectal cancer with Spearman method.Results The expression of LC3Ⅱand VEGF and the MVD count in colorectal cancer were significantly enhanced compared with adjacent tissues and adenoma tissues(P=0.000,0.000,0.000),there is no difference in the expression and count of adjacent tissues and adenoma tissues(all P>0.05).The LC3Ⅱand VEGF expression and MVD count were associated with histological differentiation,lymph node metastasis and cancer nodules,with liver metastasis and clinical stage of colorectal cancer(LC3Ⅱ:P=0.015,0.018,0.008,0.034,0.008;VEGF:P=0.034,0.043,0.006,0.009,0.002;MVD:P=0.039,0.002,0.026,0.034,0.004),there is no difference of the patient's age,gender,tumor size and depth of invasion(all P>0.05).The LC3Ⅱ,VEGF expression and MVD count did not differ in lymph node metastases,cancer nodules and liver metastases,but the difference was statistically significant compared with the primary lesions(LC3Ⅱ:P=0.037,0.036,0.037;VEGF:P=0.041,0.011,0.041;MVD:P=0.020,0.039,0.020).The correlation analysis found that the expression of LC3Ⅱwas positively correlated with the expression of vascular growth factor and the MVD count(r=0.520,P=0.000;r=0.656,P=0.000).Conclusion Inhibition of autophagy may be an auxiliary method to improve the prognosis of patients with colorectal cancer treated with anti-vascular therapy.