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中华临床医师杂志(电子版)

中华临床医师杂志(电子版) ›› 2019, Vol. 13 ›› Issue (08) : 566 -571. doi: 10.3877/cma.j.issn.1674-0785.2019.08.002

所属专题： 文献；

临床研究

FOXM1和GRP78在进展期胃癌组织中的表达及其临床意义
龚军1, 孙峰2, 金聪慧1, 葛建娟1, 宋佳烨1, 杨磊1,†()   
  1. 1. 226361　江苏南通，南通市肿瘤医院肿瘤内科
    2. 226361　江苏南通，南通市肿瘤医院检验科
  • 收稿日期:2018-09-05 出版日期:2019-04-15
  • 通信作者: 杨磊
  • 基金资助:
    国家自然基金项目(81402015); 江苏省卫生厅面上科研课题(H201455); 南通市青年医学重点人才项目(青年053)

Clinical significance of expression of FOXM1 and GRP78 proteins in advanced gastric cancer

Jun Gong1, Feng Sun2, Conghui Jin1, Jianjuan Ge1, Jiaye Song1, Lei Yang1,†()   

  1. 1. Department of Medical Oncology, Nantong Tumor Hospital, Nantong 226361, China
    2. Department of Inspecoion, Nantong Tumor Hospital, Nantong 226361, China
  • Received:2018-09-05 Published:2019-04-15
  • Corresponding author: Lei Yang
  • About author:
    Corresponding author: Yang Lei, Email:
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引用本文：

龚军, 孙峰, 金聪慧, 葛建娟, 宋佳烨, 杨磊. FOXM1和GRP78在进展期胃癌组织中的表达及其临床意义[J]. 中华临床医师杂志(电子版), 2019, 13(08): 566-571.

Jun Gong, Feng Sun, Conghui Jin, Jianjuan Ge, Jiaye Song, Lei Yang. Clinical significance of expression of FOXM1 and GRP78 proteins in advanced gastric cancer[J]. Chinese Journal of Clinicians(Electronic Edition), 2019, 13(08): 566-571.

目的

探讨进展期胃癌组织中叉头框M1（FOXM1）及葡萄糖调节蛋白78（GRP78）的表达及其临床意义。

方法

对2010年1月至2015年6月在南通市肿瘤医院行胃癌根治术的168例标本，采用免疫组织化学方法检测进展期胃癌组织及癌旁组织中FOXM1及GRP78的表达情况；应用χ2检验分析进展期胃癌病理特征与FOXM1及GRP78表达的相关性，并应用Cox单因素及多因素分析进展期胃癌预后危险因素。

结果

进展期胃癌组织中FOXM1和GRP78的表达率分别为53.57%（90/168）和67.26%（113/168），癌旁组织中二者无表达或弱阳性表达。二者表达在胃癌组织中呈正相关（r=0.41，P<0.001）。FOXM1蛋白表达与脉管癌栓（P<0.001）、淋巴结转移（P<0.001）、T分期（P=0.022）、TNM分期（P<0.001）及分化程度（P<0.001）相关，GRP78蛋白表达与脉管癌栓（P=0.003）、淋巴结转移（P=0.002）及分化程度（P<0.001）相关。FOXM1及GRP78共表达阳性患者术后总生存期显著低于共阴性者，差异具有统计学意义（χ2=35.1189，P<0.001）。FOXM1、T分期是影响进展期胃癌预后的独立危险因素。

结论

FOXM1及GRP78可能协同参与了胃癌的发生、发展，并可能成为进展期胃癌临床治疗的新靶点。

关键词: 进展期胃癌, 叉头框转录因子M1, 葡萄糖调节蛋白78
Objective

To investigate the expression of forkhead box M1 (FOXM1) and glucose-regulated protein 78 (GRP78) in advanced gastric cancer and to analyze their clinical value.

Methods

Immunohistochemical technique was used to detect the expression of FOXM1 and GRP78 proteins in cancerous and paracancerous tissues from 168 patients with advanced gastric cancer. χ2 test was used to analyze the correlation between the pathological features of advanced gastric cancer and the expression of FOXM1 and GRP78. Prognostic risk factors for advanced gastric cancer were analyzed by Cox single- and multiple-factor analyses.

Results

The positive rates of FOXM1 and GRP78 expression in advanced gastric cancer were 53.57% (90/168) and 67.26% (113/168), respectively. No or weak expression of FOXM1 and GRP78 was found in paracancerous tissues. The expression of FOXM1 was positively related to expression of GRP78 in gastric cancer tissues (r=0.41, P<0.001). The expression of FOXM1 protein was correlated with cancer embolus (P<0.001), lymph node metastasis (P<0.001), T stage (P<0.001), TNM stage (P<0.001), and tumor differentiation (P<0.001). The expression of GRP78 protein was correlated with cancer embolus (P=0.003), lymph node metastasis (P=0.002), and tumor differentiation (P<0.001). The overall survival of patients with positive expression of both FOXM1 and GRP78 was shorter than those with negative expression of both proteins (χ2=35.1189, P<0.001). FOXM1 and T stage were independent prognostic factors for advanced gastric cancer.

Conclusion

FOXM1 and GRP78 may be involved in the development and progression of gastric cancer, and they might become new targets for clinical therapy for advanced gastric cancer.

Key words: Advanced gastric cancer, Forkhead box M1, Glucose-regulated protein 78
图1 FOXM1蛋白和GRP78蛋白在进展期胃癌癌组织中表达情况　图a示FOXM1蛋白在癌旁组织中低表达（SP法，×50），图b示FOXM1蛋白在胃癌中的高表达（SP法，×50），图c示GRP78蛋白在癌旁组织中低表达（SP法，×50），图d示GRP78蛋白在胃癌中的高表达（SP法，×50）；FOX为叉头框，GRP为葡萄糖调节蛋白
图2 FOXM1和GRP78蛋白在进展期胃癌组织中表达的平均吸光度值散点图
表1 胃癌组织中FOXM1及GRP78蛋白的表达与临床参数的关系
临床参数 例数 FOXM1 GRP78
阳性 χ2值 P值 阳性 χ2值 P值
年龄（岁） ? ? 0.172 0.678 ? 0.914 0.339
? <50 28 16 ? ? 21 ? ?
? ≥50 140 74 ? ? 92 ? ?
性别 ? ? 0.286 0.593 ? 0.015 0.901
? 男 115 60 ? ? 77 ? ?
? 女 53 30 ? ? 36 ? ?
脉管癌栓 ? ? 15.520 <0.001 ? 8.831 0.003
? 有 46 36 ? ? 39 ? ?
? 无 122 54 ? ? 74 ? ?
神经侵犯 ? ? 0.054 0.816 ? 0.350 0.554
? 有 77 42 ? ? 50 ? ?
? 无 91 48 ? ? 63 ? ?
TNM分期 ? ? 24.463 <0.001 ? 3.949 0.139
? Ⅰ期 20 9 ? ? 13 ? ?
? Ⅱ期 69 23 ? ? 41 ? ?
? Ⅲ期 79 58 ? ? 59 ? ?
T分期 ? ? 7.675 0.022 ? 1.165 0.559
? T2 40 21 ? ? 29 ? ?
? T3 79 35 ? ? 50 ? ?
? T4 49 34 ? ? 34 ? ?
分化程度 ? ? 17.063 <0.001 ? 117.596 <0.001
? 高 9 3 ? ? 1 ? ?
? 中 44 13 ? ? 4 ? ?
? 低 115 74 ? ? 108 ? ?
淋巴结转移 ? ? 27.882 <0.001 ? 15.034 0.002
? N0 60 20 ? ? 36 ? ?
? N1 23 8 ? ? 11 ? ?
? N2 45 36 ? ? 40 ? ?
? N3 40 26 ? ? 26 ? ?
表2 单因素和多因素回归分析影响胃癌术后辅助性化疗患者的无疾病生存期的相关预后因子
临床资料 单因素分析 多因素分析
P>|z| HR值 95%CI P>|z| HR值 95%CI
性别（女 vs男） 0.8 1.058 0.682~1.641 - - -
发病年龄（<50岁 vs ≥50岁） 0.078 1.624 0.948~2.784 - - -
分化程度（G期，中高分化 vs低分化） 0.019 0.601 0.393~0.919 0.562 1.28 0.556~2.947
浸润深度（T期，T2 vs T3-4） 0.005 0.491 0.299~0.804 0.013 0.351 0.154~0.804
区域淋巴结转移（N期，N0 vs N1-3） 0.005 0.508 0.316~0.816 1.000 1.000 0.483~2.068
TNM分期（Ⅰ期 vs Ⅱ＋Ⅲ期） <0.001 0.475 0.305~0.738 0.285 0.672 0.324~1.393
脉管癌栓（无 vs有） 0.011 0.529 0.324~0.863 0.639 0.878 0.511~1.509
神经侵犯（否 vs是） 0.465 2.014 1.269~3.195 - - -
GRP78蛋白表达（低或无表达 vs高表达） 0.009 0.566 0.37~0.865 0.053 0.447 0.225~1.008
FOXM1蛋白表达（低或无表达 vs高表达） <0.001 0.267 0.173~0.414 <0.001 0.266 0.164~0.429
图3 GRP78和FOXM1共阳性与共阴性患者的总生存曲线
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