结肠直肠癌中APRIL表达与临床病理及预后的关系

The relationship of A Proliferation-Inducing Ligand expression with the clinical pathology and prognosis in colorectal carcinoma

目的 探讨增殖诱导配体（APRIL）在结肠直肠癌（CRC）组织中的表达,其与临床病理及预后的相关性.方法 收集南通大学附属医院病理科120例CRC病例及其相关的临床资料,将组织标本制作成组织芯片,采用鼠抗人APRIL单克隆抗体,经免疫组织化学Envision法检测组织芯片中APRIL蛋白表达情况,结合临床病理参数和随访资料进行统计学分析.结果 免疫组化结果提示CRC肿瘤组织中APRIL蛋白表达阳性率为83.33％ （100/120）,癌旁正常肠黏膜组织表达阳性率为12.5％ （15/120）,两者差异有统计学意义（P〈0.001）.APRIL在CRC中的表达与TNM分期（χ^2=10.222,P=0.006）及肿瘤浸润深度（χ^2=5.987,P=0.014）有关.Kaplan-Meier生存曲线显示APRIL高表达组比低表达组5年生存率低.单因素生存分析显示APRIL表达程度（P 〈0.001）、肿瘤分化程度（P=0.033）、TNM分期（P〈0.001）、肿瘤浸润深度（P=0.011）、淋巴结转移（P 〈0.001）及术前血CEA水平（P=0.003）与术后生存时间相关.多因素COX比例风险回归模型分析进一步显示APRIL表达程度（P=0.001）、肿瘤分化程度（P=0.005）、TNM分期（P=0.001）及术前血癌胚抗原（CEA）水平（P=0.039）为其独立的预后因素.结论 APRIL在CRC肿瘤组织中表达与TNM分期及肿瘤浸润深度密切相关,其高表达提示患者预后不良,是CRC患者独立的预后因子之一,可能成为结直肠癌患者潜在的治疗靶点.

Objective To investigate the protein expression of A Proliferation-Inducing Ligand （APRIL） in colorectal cancer （CRC） tissue,and its correlation with clinical pathology and prognosis.Methods One hundred and twenty cases of CRC tissue and related clinical data were collected from the Department of Pathology of Affiliated Hospital of Nantong University.The specimens were made into tissue microarray.The protein expression of APRIL was detected by Envision immunohistochemistry.The relationship of the protein expression of APRIL with clinicopathological parameters and follow-up data were statistically analyzed.Results APRIL protein expression positive rate of CRC tissue and cancer adjacent normal mucosal tissue were 83.33% （100/120） and 12.5% （15/120）,with a statistical significance （P 〈 0.001）.The expression of APRIL was related to TNM staging （χ^2=10.222,P =0.006） and the depth of tumor invasion （χ^2 =5.987,P =0.014）.Kaplan-Meier survival curves showed that five years survival rate of high APRIL expression group was lower than that of low APRIL expression group.Univariate survival analysis showed that the expression of APRIL （P 〈 0.001）,the degree of tumor differentiation （P =0.033）,TNM staging （P 〈 0.001）,depth of tumor invasion （P =0.011）,lymph node metastasis （P 〈 0.001） and serum CEA （P =0.003） time were associated with postoperative survival.Multivariate COX proportional hazard regression model analysis further revealed the expression of APRIL （P =0.001）,the degree of tumor differentiation （P =0.005）,TNM staging （P =0.001） and serum CEA （P =0.039） were the independent risk factors for prognosis.Conclusion The expression of APRIL in CRC tumor tissue is closely related to TNM stage and depth of tumor invasion.The high expression of APRIL prompts bad prognosis.APRIL is one of the independent prognostic factors in patients with CRC,and could be a potential target for the therapy of CRC.