GRP78和pERK在胃癌及非胃癌组织中的表达及临床意义

doi:10.3969/j.issn.1007-3969.2013.11.006

中国癌症杂志 ›› 2013, Vol. 23 ›› Issue (11): 885-891.doi: 10.3969/j.issn.1007-3969.2013.11.006

GRP78和pERK在胃癌及非胃癌组织中的表达及临床意义

彭春雷1,杨书云2,季进锋1,徐薇薇1,季从飞1,王建红1,谭清和1,杨磊1

1.南通大学附属肿瘤医院肿瘤内科，江苏南通226361；
2.南通大学附属肿瘤医院病理科，江苏南通226361

出版日期:2013-11-25 发布日期:2014-02-18
通信作者: 杨磊　E-mail:leiyang.53@163.com
基金资助:
南通市科技局指令性课题(No：S2010024)

The expression and clinical significance of GRP78 and pERK in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis

PENG Chun-lei¹,YANG Shu-yun²,JI Jin-feng¹,XU Wei-wei¹,JI Cong-fei¹,WANG Jian-hong¹,TAN Qing-he¹,YANG Lei¹

1. Department of Medical Oncology, Nantong University Affiliated Tumor Hospital, Nantong Jiangsu 226361, China;
2. Department of Pathology, Nantong University Affiliated Tumor Hospital, Nantong Jiangsu 226361, China

Published:2013-11-25 Online:2014-02-18
Contact: YANG Lei E-mail: leiyang.53@163.com

摘要/Abstract

摘要：

背景与目的：在胃癌的发生、发展过程中，内质网应激、细胞的修复及凋亡是重要的病理生理过程，而GRP78与pERK在其中发挥了重要的作用。研究葡萄糖调节蛋白78(glucose-regulatedproteins 78，GRP78)和磷酸化细胞外信号调节激酶(pERK)在胃腺癌、慢性萎缩性胃炎及浅表性胃炎组织中的表达，研究它们与胃癌发生、发展的关系。方法：RT-PCR法检测各25例胃腺癌、慢性萎缩性胃炎和浅表性胃炎新鲜组织中GRP78、pERK基因表达；免疫组化法分别检测各60例胃腺癌、慢性萎缩性胃炎和浅表性胃炎组织中GRP78、pERK蛋白表达，并分析其蛋白表达与临床病理参数间的相关性。结果：RTPCR半定量结果显示，胃癌组织中GRP78及pERK mRNA的相对表达水平(1.26±0.18、2.35±0.36)均明显高于慢性萎缩性胃炎组织(0.89±0.25、1.18±0.25)及浅表性胃炎组织(0.29±0.09、0.68±0.10)，差异有统计学意义(P＜0.01)。免疫组织化学结果显示，GRP78及pERK蛋白在胃癌组织中的表达率(78.3%、88.3%)亦均高于慢性萎缩性胃炎(46.6%、43.3%)及浅表性胃炎组织(6.7%、5.0%)，差异有统计学意义(P＜0.01)。胃癌组织中GRP78及pERK蛋白表达与胃癌分化程度、分期、淋巴结转移等有明显相关性。GRP78及pERK基因及蛋白表达水平在胃癌中均呈正相关(基因：r=0.307，P=0.000；蛋白：r=0.368，P=0.000)。单因素分析结果显示：组织学分级、浸润深度、TNM分期、淋巴结转移、GRP78高表达及pERK高表达与胃癌预后有关(P均＜0.05)。浸润全层、低分化、TNM分期晚、有淋巴结转移、GRP78高表达及pERK高表达患者生存时间短。多因素生存分析结果结果显示：GRP78高表达与GRP78低表达相比生存时间差异有统计学意义(P＜0.001)。GRP78高表达的胃癌患者生存时间短，提示GRP78是负性的预后因子。结论：GRP78和pERK在胃癌中高表达，GRP78和pERK在正常细胞向恶性细胞转化的过程中可能扮演了重要角色，检测pERK和GRP78的表达可能有助于对胃腺癌的预防、早期诊断及预后判断，同时为胃癌治疗寻找新的靶点。

关键词: 葡萄糖调节蛋白78, 磷酸化细胞外信号调节激酶, 胃癌

Abstract:

Background and purpose: In the process of gastric cancer development, cytothesis and apoptosis, and endoplasmic reticulum stress (ERS) are very important pathological processes. Glucose regulated protein 78 (GRP78) and phosphorylated form of extracellular signal-regulated protein kinase (pERK) play important roles in it. This study aimed to investigate the expression of GRP78 and pERK in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis, and the role of GRP78 and pERK in the development of gastric adenocarcinoma. Methods: Gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis tissues in 60 cases respectively were employed in the study. We chose 25 fresh tissue samples from each group, and the level of GRP78 and pERK mRNA in different tissues were detected by RT-PCR assay. The expressions of GRP78 and pERK in different paraffin samples were detected using immunohistochemistry assay. In addition, the relationships between GRP78 and pERK expression and age, gender, differentiation, invasion, disease stage, and lymphoid node metastasis were analyzed. Results: The expression level of GRP78 and pERK mRNA in gastric adenocarcinoma(1.26±0.18, 2.35±0.36) were significantly higher than chronic atrophic gastritis (0.89±0.25, 1.18±0.25) and superficial gastritis (0.29±0.09, 0.68±0.10, P<0.01). The positive ratio of GRP78 expression in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis were 78.3%, 46.6%, 6.7%. The positive ratios of pERK expression were 88.3%, 43.3%, 5.0%, respectively. The GRP78 and pERK expression in different tissues were significantly different (P<0.01). GRP78 and pERK expression were positively correlated with differentiation, disease stage and lymph node metastasis. There was a positive correlation between the gene and protein expression of GRP78 and pERK with a Pearson correlation value of 0.307 and 0.368, respectively. Both univariate and multivariate analysis revealed that GRP78 was related to the prognosis of gastric adenocarcinoma. Conclusion: GRP78 and pERK may play an important role in the transition of normal gastric cells to malignant cells. The expression of these two genes enhances tumor progression. Overexpression of GRP78 and pERK is significantly correlated with poor prognosis in patients with gastric adenocarcinoma. The determination of the expression of GRP78 and pERK might be helpful for the prevention, early diagnosis of gastric carcinoma. Particularly, GRP78 is valuable for the judgement of prognosis, and might be a new target for the treatment of gastric adenocarcinoma.

Key words: GRP78, pERK, Gastric adenocarcinoma

彭春雷,杨书云,季进锋,徐薇薇,季从飞,王建红,谭清和,杨磊. GRP78和pERK在胃癌及非胃癌组织中的表达及临床意义[J]. 中国癌症杂志, 2013, 23(11): 885-891.

PENG Chun-lei,YANG Shu-yun,JI Jin-feng,XU Wei-wei,JI Cong-fei,WANG Jian-hong,TAN Qing-he,YANG Lei. The expression and clinical significance of GRP78 and pERK in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis[J]. China Oncology, 2013, 23(11): 885-891.

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GRP78和pERK在胃癌及非胃癌组织中的表达及临床意义

The expression and clinical significance of GRP78 and pERK in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis

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