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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

27卷

期数:

2021年05期

页码:

502-510,553

栏目:

临床医学

出版日期:

2021-09-10

文章信息/Info

Title:

The significance of tumor-associated macrophages and Helicobacter pylori infection in the prognosis of patients with stage Ⅲ gastric adenocarcinoma at various sites

文章编号:

1006-8147(2021)05-0502-10

作者:

王月洁¹; 魏枫¹; 任秀宝¹; 2

（天津医科大学肿瘤医院1.生物技术研究室；2.生物治疗科，国家肿瘤临床医学研究中心，天津市“肿瘤防治”重点实验室，天津市恶性肿瘤临床医学研究中心，天津市肿瘤免疫与生物治疗重点实验室，天津 ³000⁶0）

Author(s):

WANG Yue-jie¹; WEI Feng¹; REN Xiu-bao¹; 2

（1.Department of Immunology；2.Department of Biotherapy，Tianjin Medical University，Cancer Institute and Hospital，National Clinical Research Center for Cancer， Key Laboratory of Cancer Prevention and Therapy， Tianjin′s Clinical Research Center for Cancer， K

关键词:

幽门螺杆菌; 胃肿瘤; 腺癌; 抗原; CD68; 抗原; CD163; 抗原; CD66b

Keywords:

Helicobacter pylori; stomach neoplasms; adenocarcinoma; antigens; CD68;  antigens; CD163; antigens; CD66b

分类号:

R735.2

DOI:

-

文献标志码:

A

摘要:

目的：分析肿瘤相关巨噬细胞(TAMs)标志物(抗原CD68和CD163)表达和幽门螺杆菌(Hp)感染对不同部位Ⅲ期胃腺癌患者预后的影响。方法：收集2012年1月—2014年12月天津医科大学肿瘤医院胃部肿瘤科300例确诊为Ⅲ期胃腺癌患者的病例资料（根据发生部位的不同，分为胃底贲门癌组、胃体癌组和胃窦癌组，各100例）。比较3组患者一般资料；免疫组化染色法检测患者的肿瘤组织中有无Hp感染、CD68+TAMs以及CD163+TAMs的分布情况；根据CD68+TAMs的浸润情况将胃腺癌分为Ⅰ型（癌巢边缘浸润数量多于癌巢）和Ⅱ型（癌巢浸润数量多于癌巢边缘），利用Kaplan-Meier法分析Ⅰ型和Ⅱ型胃腺癌患者预后的关系。然后分析Ⅰ型和Ⅱ型胃腺癌患者的Hp阳性表达率以及两组临床病理特征的关系；分析部位、年龄、饮酒、中性粒细胞、分型和Hp感染之间的相关性；利用Kaplan-Meier法分析Ⅰ型和Ⅱ型不同部位胃腺癌患者Hp与预后的关系。结果：胃底贲门癌组患者肿瘤显著大于胃窦癌组和胃体癌组（t=5.972，P<0.05）；胃窦癌组患者饮酒人数多于胃体癌组（χ2=6.742，P<0.05）；CD68+和CD163+TAMs在胃窦癌癌巢的相对表达水平高于癌巢浸润边缘；在胃底贲门癌癌巢浸润边缘的相对表达高于癌巢；在胃体癌癌巢浸润边缘的相对表达高于癌巢，差异均有统计学意义（H=136.06、124.99、142.17、91.16，均P<0.01）；CD68+和CD163+TAMs在癌巢浸润边缘多者预后不良（χ2=6.289、4.153、5.979，均P<0.05）；Ⅱ型胃腺癌患者累计生存率和无病生存率较Ⅰ型高（χ2=4.950、5.601，均P<0.05）；肿瘤大小与年龄、发生部位有关系（r=-0.162、-0.115，均P<0.05）；分型与发生部位、中性粒细胞显著相关（r=0.745、0.231，均P<0.01）；Hp与发生部位、分型有关（r=0.141、0.110，均P<0.05）；发生在胃体和胃窦部、肿瘤<4 cm、无淋巴结转移、中性粒细胞水平高的Ⅱ型胃腺癌患者Hp阳性表达率高，且预后较好（χ2=20.168、2.365、19.247、18.972，均P<0.05）。结论:TAMs标志物（抗原CD68和CD163）在癌巢浸润数量多对不同部位的Ⅲ期胃腺癌均是有利因素，另外，Hp阳性也是预测胃体癌和胃窦癌的良好指标。

Abstract:

Objective: To analyze the effects of tumor-associated macrophages（TAMs） markers(antigens CD68 and CD163) expression and Helicobacter pylori（Hp） infection on the prognosis of patients with stage Ⅲ gastric adenocarcinoma at different locations. Methods:From January 2012 to December 2014，300 cases of patients diagnosed with stage Ⅲ gastric adenocarcinoma in the Department of Gastric Oncology， Tianjin Medical University Cancer Hospital were collected（they were divided into gastric fundus and cardia cancer group， gastric body cancer group and gastric antrum cancer group，100 cases in each group）．The general information of the three groups of patients were compared；immunohistochemical staining was used to detect the presence or absence of Hp infection， CD68+ TAMs and the distribution of CD163+TAMs in the tumor tissues of the patients; according to the infiltration of CD68+TAMs， gastric adenocarcinoma was classified into typeⅠ（the number of infiltrates at the edge of cancer nests more than that of cancer nests） and type Ⅱ（the number of infiltrates in cancer nests more than at the edges of cancer nests）. Kaplan-Meier method was used to analyze the relationship between the prognosis of patients with type Ⅰand typeⅡgastric adenocarcinoma. Then the positive expression rate of Hp in patients with typeⅠand typeⅡgastric adenocarcinoma and the relationship between the two groups of clinicopathological characteristics were analyzed.The correlation between location，age，alcohol consumption，neutrophils，type and Hp infection were analyzed. Kaplan-Meier method was used to analyze the relationship between Hp and prognosis in patients with gastric adenocarcinoma at different sites of typeⅠand type Ⅱ. Results:The tumors in the gastric cardia cancer group were significantly larger than those in the gastric antral cancer group and the gastric body cancer group（t=5.972，P<0.05）； the alcohol consumption of the gastric antral cancer group was more than the gastric body cancer group（χ2=6.742，P<0.05）； the relative expression of CD68+ and CD163+TAMs in gastric antral cancer nests were higher than the infiltration margins of cancer nests；the relative expression of cancer nest infiltration margin in gastric cardia cancer were higher than those in cancer nest；at the cancer nest infiltration margin of gastric body，the relative expression of were higher than those in cancer nest，the difference was statistically significant（H=136.06，124.99，142.17，91.16，all P<0.01).CD68+ and CD163+TAMs at the edge of the cancer nest had a poor prognosis（χ2=6.289，4.153，5.979，all P<0.05）；the cumulative survival rate and disease-free survival rate of patients with type Ⅱ gastric adenocarcinoma were higher than those with type Ⅰ（χ2=4.950，5.601，both P<0.05）； tumor size was related to age and site of occurrence（r=-0.162，-0.115，both P<0.05）；classification was significantly related to site of occurrence and neutrophils（r=0.745， 0.231，both P<0.01）； Hp was related to site and type（r=0.141，0.110，both P<0.05）. The patients with type Ⅱ gastric adenocarcinoma occurred in the gastric corpus and antrum，with tumor <4 cm，no lymph node metastasis，high levels of neutrophils had a high positive expression rate of Hp and a good prognosis（χ2=20.168，2.365，19.247，18.972，all P<0.05）． Conclusion:The large number of TAMs markers（antigens CD68 and CD163） infiltrating cancer nests are favorable factors for stage Ⅲ gastric adenocarcinoma at different sites. In addition，for gastric body cancer and gastric antrum cancer，Hp positive is also a good predictive indicator.

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备注/Memo

备注/Memo:

基金项目 国家重点R&D计划(2018YFC1313400);国家重大科技专项“重大新药开发”(2018ZX09201-05)
作者简介 王月洁(1995-)，女，硕士在读，研究方向：肿瘤的生物治疗；通信作者:任秀宝，E-mail:renxiubao@tjmuch.com。

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更新日期/Last Update: 2021-09-01