羧基张力蛋白在结直肠癌组织中的表达及其临床意义

Expression and clinical significance of C-terminal tensin like protein in colorectal cancer

  • 摘要: 目的:探讨结直肠癌患者中羧基张力(CTEN)蛋白的表达及其与结直肠癌患者临床病理因素和预后的关系。
    方法:采用回顾性病例对照研究方法。收集2010年1月至2012年12月江苏大学附属医院收治153例结直肠癌患者的临床病理资料。采用免疫组织化学染色检测结直肠癌及其癌旁组织中CTEN蛋白的表达。观察指标:(1)免疫组织化学染色检测结直肠癌组织和癌旁组织中CTEN蛋白表达情况。(2)结直肠癌组织中CTEN蛋白表达与结直肠癌患者临床病理因素的关系。(3)结直肠癌组织中CTEN蛋白表达与患者预后的关系。术后采用电话方式进行随访,了解患者生存情况。随访时间截至2015年5月。计数资料采用双侧x2检验。采用Kaplan-Meier法绘制生存曲线,Logrank检验进行生存分析。单因素及多因素COX比例风险模型分析预后因素。
    结果:(1)CTEN蛋白在结直肠癌组织和癌旁组织细胞中主要表达于细胞质,其阳性表达率分别为92.16%(141/153)和20.26%(31/153),两者比较,差异有统计学意义(χ2=160.647,P<0.05)。35.95%(55/153)的结直肠癌组织和6.54%(10/153)的癌旁组织中CTEN蛋白高表达,两者比较,差异有统计学意义(χ2=39.561,P<0.05)。(2)肿瘤最大直径<5 cm和≥5 cm的结直肠癌组织中CTEN蛋白高表达率分别为16.30%和63.57%,在TNM分期中的Ⅰ~Ⅲ、Ⅳ期中分别为31.15%和54.84%,在无和有神经和(或)脉管侵犯中分别为26.23%和42.39%,上述指标比较,差异均有统计学意义(χ2=38.670,6.026,4.161,P<0.05)。(3)153例结直肠癌患者中,109例术后接受化疗和(或)放疗和(或)生物靶向治疗。55例CTEN蛋白高表达患者中,接受术后化疗和(或)放疗和(或)生物靶向治疗 41例;98例CTEN蛋白低表达者中为68例,两者比较,差异无统计学意义(χ2=0.457,P>0.05)。153例患者均获得随访,随访时间为4.8~62.3个月,中位随访时间为27.5个月。CTEN蛋白高表达患者的3年无瘤生存率(Ⅰ~Ⅲ期)和总体生存率(Ⅰ~Ⅳ期)分别为52.23%和39.71%,CTEN蛋白低表达患者分别为76.89%和74.12%,两者上述指标比较,差异均有统计学意义(χ2=15.727,15.131,P<0.05)。Ⅳ期结直肠癌患者均未达到R0切除,未纳入无瘤生存率统计。单因素分析结果显示:肿瘤最大直径、组织学分级、TNM分期、神经和(或)脉管侵犯及CTEN蛋白表达水平与结直肠癌患者预后显著相关(HR=4.39,2.08,5.73,3.56,2.03,95%可信区间:2.49~7.74,2.21~3.55,3.29~9.98,1.82~6.95,1.18~3.48, P<0.05)。多因素分析结果显示:肿瘤最大直径≥5 cm、TNM分期为Ⅳ期及CTEN蛋白高表达水平是结直肠癌患者预后不良的独立危险因素(HR=2.24,3.57,2.03,95%可信区间:1.13~4.20,1.94~6.59,1.03~3.98,P<0.05)。
    结论:CTEN蛋白在结肠癌组织中较癌旁组织表达上调,在肿瘤最大直径≥5 cm,TNM分期为Ⅳ期及有神经和(或)脉管侵犯的结直肠癌组织中表达率明显增高,CTEN蛋白高表达是独立的预后预测因素。

     

    Abstract: Objective:To investigate the expression of Cterminal tensinlike (CTEN) protein and its correlations with clinicopathological characteristics and prognosis in patients with colorectal cancer.
    Methods: The retrospective casecontrol study was adopted. The clinical data of 153 patients with colorectal cancer who were admitted to the Affiliated Hospital of Jiangsu University between January 2010 and December 2012 were collected. The expression of CTEN protein were detected by immunohistochemistry. Observed indices included: (1) expression of CTEN protein was detected by immunohistochemistry. (2) Relationships between the expressions of CTEN protein and clinicopathological characteristics of patients. (3) Relationships between the expressions of CTEN protein and prognosis of patients. The followup of telephone interview was performed to detect survival of patients untill May 2015. Count data were analyzed using twosided chisquare test. Survival curve was drawn using the KaplanMeier method, and survival analyses was done using the Logrank test. Univariate and multivariate analyses of prognosis were done using COX regression model.
    Results: (1) Expressions of CTEN protein in cancer tissues and adjacent tissues were located at the cytoplasms. The positive expression rate of CTEN protein was 92.16%(141/153) and 20.26%(31/153) in cancer tissues and adjacent tissues, respectively, with a statistically significant difference (χ2=160.647, P<0.05). High expression of CTEN protein was 35.95% (55/153) and 6.54% (10/153) in cancer tissues and adjacent tissues, respectively, with a significant difference (χ2=39.561, P<0.05). (2) The high expression rate of CTEN protein was 16.30% and 63.57% in tumor with maximum diameter<5 cm and ≥5 cm, 31.15% and 54.84% in the Ⅰ-Ⅲ and Ⅳ stages of TNM stage, 42.39% and 26.23% in tumor with and without perineural and/or vascular invasion, respectively, showing significant differences (χ2=38.670, 6.026, 4.161, P<0.05). (3) Of 153 patients with colorectal cancer, 109 received chemotherapy, radiotherapy and/or biological targeted therapy after surgery. There were 41 of 55 patients with high expression of CTEN protein and 68 of 98 patients with low expression of CTEN protein receiving chemotherapy, radiotherapy and/or biological targeted therapy after surgery, respectively, showing no significant difference (χ2=0.457, P>0.05). All the 153 patients were followed up for 4.8-62.3 months with a median time of 27.5 months. The 3year tumorfree survival (Ⅰ-Ⅲ stages) and overall survival (Ⅰ-Ⅳ stages) rates were 52.23% and 39.71% of patients with high expression of CTEN protein, 76.89% and 74.12% in patients with low expression of CTEN protein, respectively, showing significant differences (χ2=15.727, 15.131, P<0.05). Patients with colorectal cancer of Ⅳ stages didn′t achieve R0 resection and were not involved in tumorfree survival. Results of univariate analysis showed that tumor maximum diameter, histologic grade, TNM stage, tumor with perineural and/or vascular invasion and expression of CTEN protein were associated with the prognosis of patients [HR=4.39, 2.08, 5.73, 3.56, 2.03, 95% confidence interval (CI): 2.49-7.74, 2.21-3.55, 3.29-9.98, 1.82-6.95, 1.18-3.48, P<0.05]. Results of multivariate analysis showed that maximum diameter≥ 5 cm, Ⅳ stage of TNM stage and high expression CTEN protein were independent risk factors affecting the poor prognosis of patients with colorectal cancer (HR=2.24, 3.57, 2.03, 95 %CI: 1.13-4.20, 1.94-6.59, 1.03-3.98, P<0.05).
    Conclusions:The expression of CTEN protein is upregelated in colorectal cancer compared with adjacent normal tissues. There is increased expression of CTEN protein in colorectal cancer tissues with maximum diameter of tumor ≥5 cm, high TNM stage and perineural and/or vascular invasion. High expression of CTEN protein is also an independent predicting factor of prognosis.

     

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