中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (3): 243-250.doi: 10.19401/j.cnki.1007-3639.2022.03.007

• 论著 • 上一篇    下一篇

错配修复蛋白联合血清肿瘤标志物与Ki-67增殖指数对结直肠癌预后的临床价值

陈玺1, 曾晓颖2, 陈佳艳1, 刘菲1, 唐曦1()   

  1. 1.复旦大学附属华东医院肿瘤科,上海 200040
    2.上海市静安区统战部,上海 200041
  • 收稿日期:2022-01-03 修回日期:2022-02-08 出版日期:2022-03-30 发布日期:2022-04-02
  • 通信作者: 唐曦 E-mail:olivia9tang@126.com

The clinical value of mismatch repair protein combined with serum tumor markers and Ki-67 proliferation index in the prognostic evaluation of colorectal cancer

CHEN Xi1, ZENG Xiaoying2, CHEN Jiayan1, LIU Fei1, TANG Xi1()   

  1. 1. Department of Oncology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
    2. Shanghai Jing'an District United Front Work Department, Shanghai 200041, China
  • Received:2022-01-03 Revised:2022-02-08 Published:2022-03-30 Online:2022-04-02
  • Contact: TANG Xi E-mail:olivia9tang@126.com

摘要:

背景与目的:结直肠癌是消化系统常见的恶性肿瘤之一,近年来中国结直肠癌发病率显著升高。各项临床与病理学指标对于结直肠癌的诊断、临床分期及预后的判断提供了帮助。探讨错配修复蛋白表达联合血清肿瘤标志物与Ki-67增殖指数在结直肠癌中的相关性及对预后判断的临床价值。方法:收集复旦大学附属华东医院2014年7月—2018年6月收治的234例结直肠癌手术患者,分析其术前血清标本中肿瘤标志物癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原(carbohydrate antigen,CA)19-9、CA72-4、CA12-5水平及手术标本组织中的Ki-67增殖指数与错配修复蛋白的表达率,与结直肠癌临床病理学特征和预后的关系。结果:在234例结直肠癌患者术后标本中发生错配修复蛋白缺失表达(deficient mismatch repair,dMMR)的共29例(12.4%),错配修复蛋白正常表达(proficient mismatch repair,pMMR)的有205例(87.6%)。在临床病理学指标的相关性分析中dMMR组与pMMR组在肿瘤原发部位、分化类型、分期、T分期、淋巴结转移方面的差异有统计学意义(P<0.05)。在相关性分析中dMMR组与pMMR组在Ki-67增殖指数、术前CEA、CA72-4的水平差异有统计学意义(P<0.05)。在单因素预后分析中,淋巴结转移组,分期较晚组生存率低,差异有统计学意义(P<0.001)。在错配修复蛋白组中dMMR组的生存率为100%,pMMR组的生存率为83%,差异有统计学意义(P<0.05)。术前肿瘤标志物组在预后分析中CEA、CA72-4对生存率的影响差异有统计学意义(P<0.05)。通过对在单因素分析中影响结直肠癌患者预后的5组变量进行多因素COX回归分析发现,分期与术前CA72-4水平与预后显著相关(P<0.05)。提示分期和术前CA72-4水平是影响患者预后的危险因素。结论:dMMR更多见于原发右半结肠的结肠癌,在低分化腺癌及黏液腺癌类型较差的肿瘤多见,对结直肠癌患者的预后评估具有一定的意义。

关键词: 错配修复蛋白, 血清肿瘤标志物, Ki-67增殖指数, 结直肠癌, 预后

Abstract:

Background and purpose: Colorectal cancer is one of the most common malignant tumors of digestive system. The incidence of colorectal cancer has increased significantly in China in recent years. Various clinical and pathological indicators are helpful for the diagnosis, clinical staging and prognostic evaluation of colorectal cancer. This study aimed to observe the correlation between the expression of mismatch repair protein and serum tumor markers and Ki-67 proliferation index in colorectal cancer, and to analyze the prognostic value of mismatch repair protein, serum tumor markers and Ki-67 proliferation index. Methods: Data of 234 patients with colorectal cancer were collected after surgery in Huadong Hospital Affiliated to Fudan University from July 2014 to June 2018, and the preoperative serum levels of tumor markers (CEA, CA19-9, CA72-4, CA12-5), Ki-67 proliferation index and mismatch repair protein expression rate in surgical specimens were analyzed, in order to find the relationship between these clinicopathological features and prognosis of colorectal cancer. Results: Among 234 postoperative specimens of colorectal cancer patients, a total of 29 cases (12.4%) had defective expression of mismatch repair protein (dMMR), and 205 cases (87.6%) had normal expression of mismatch repair protein (pMMR). In the correlation analysis of clinicopathological features, there were statistically significant differences in tumor primary site, differentiation type, stage, T stage and lymph node metastasis between dMMR group and pMMR group (P<0.05). In the correlation analysis of the observed indicators, the differences in Ki-67 proliferation index, preoperative CEA and CA72-4 levels between dMMR group and pMMR group were statistically significant (P<0.05). Among the univariate prognostic analyses, the overall survival rate was significantly lower in the lymph node metastasis group and the advanced stage group (P<0.001). There was significant difference in overall survival rate between dMMR group (100%) and pMMR group (83%) (P<0.05). In the prognostic analysis of the preoperative tumor markers, CEA and CA72-4 levels had prognostic value in survival analysis (P<0.05). Multivariate COX regression analysis of 5 variables showed no significant correlation between expression of mismatch repair protein and lymph node metastasis in prognostic analysis, while significant correlation between staging and preoperative CA72-4 level was found in prognostic analysis (P<0.05). It was suggested that staging and preoperative CA72-4 level were the most important risk factors affecting the prognosis of colorectal cancer patients. Conclusion: dMMR was more common in right-sided colon cancer and in poorly differentiated adenocarcinoma and mucinous adenocarcinoma with poor type. T stage was late, while general pathological stage was early. Lymph node metastasis was rare. In dMMR group, Ki-67 proliferation index was mostly below the mean level (<70% expression), most patients had normal preoperative CEA level and elevated preoperative CA72-4 level. The dMMR group had a higher survival rate compared with the pMMR group, and later stage and increased preoperative CA72-4 level were risk factors affecting prognosis of patients. The expression deficiency of mismatch repair protein has certain prognostic value in patients with colorectal cancer.

Key words: Mismatch repair protein, Serum tumor marker, Ki-67 proliferation index, Colorectal cancer, Prognosis

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