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. 2021 Jun 28;46(6):575-582.
doi: 10.11817/j.issn.1672-7347.2021.200733.

Expression of Wnt3, β - catenin and MMP - 7 in gastric cancer and precancerous lesions and their correlations with Helicobacter pylori infection

[Article in English, Chinese]
Zhen Zhou  1 , Guannan Ye  2 , Jin Peng  2 , Bule He  2 , Saiqun Xu  2 , Wenling Fan  2 , Weining Wang  3
Affiliations

Expression of Wnt3, β - catenin and MMP - 7 in gastric cancer and precancerous lesions and their correlations with Helicobacter pylori infection

[Article in English, Chinese]
Zhen Zhou et al. Zhong Nan Da Xue Xue Bao Yi Xue Ban. .

Abstract
in English, Chinese

Objectives: To compare the expression of the Wnt signaling-associated proteins (Wnt3, β-catenin, MMP-7) in gastric cancer and precancerous lesions with positive and negative Helicobacter pylori (H.pylori, Hp) infection, and to further explore the mechanisms underlying the Wnt signaling pathway involving in the formation of gastric cancer and its relationship with Hp infection.

Methods: The complete paraffin samples with pathologically confirmed diagnosis, who came from the First Hospital of Changsha from January 2018 to April 2020, were collected. All samples were randomly divided into a gastric cancer group (n=57), a precancerous lesion group (n=84), and a chronic superficial gastritis group (n=25). Improved Giemsa staining was used to detect Hp infection, and according the results of Hp infection the above groups were divided into a Hp positive subgroup and a negative subgroup. The expressions of Wnt3, β-catenin and MMP-7 were examined with immunohistochemistry.

Results: The Wnt3, β-catenin, and MMP-7 were highly expressed in the gastric cancer group and the gastric precancerous lesion group. The Wnt3 and MMP-7 were highly expressed in cytoplasm, and β-catenin showed a tendency of cell membrane transferring to cytoplasm and nucleus, which was characterized by "nuclear translocation". The positive rates of the Wnt3, β-catenin, and MMP-7 expressions in the gastric cancer group were higher than those in the precancerous lesion group and the chronic superficial gastritis group (all P<0.05), which showed a gradually increasing trend with the deterioration of differentiation degree. In addition, the expressions of Wnt3, β-catenin, and MMP-7 in the Hp positive subgroup in the gastric cancer group and the precancerous lesion group were higher than those in the Hp negative subgroup (all P<0.05).

Conclusions: Aberrant activation of Wnt signaling pathway is involved in the occurrence and development of precancerous lesions and gastric cancer, and which is related with Hp infection. Meanwhile, the Wnt3, β-catenin and MMP-7 may be used as molecular markers for early diagnosis of gastric cancer and indicators to judge the degree of differentiation and malignancy of gastric cancer.

目的: 对比幽门螺杆菌(Helicobacter pylori，Hp)阳性及阴性胃癌和癌前病变组织中Wnt信号相关蛋白[Wnt3、β-连环蛋白(β-catenin)、基质金属蛋白酶-7(matrix metalloproteinase-7，MMP-7)]的表达，探讨Wnt信号通路参与胃癌形成的机制及其与Hp之间的关系。方法: 收集长沙市第一医院病理科2018年1月至2020年4月保存完整的已经病理确诊的石蜡标本，分为胃癌组(n=57)、癌前病变组(n=84)和慢性浅表性胃炎组(n=25)，各组标本均用改良Giemsa染色检测Hp感染后再分成Hp阳性亚组和Hp阴性亚组，采用免疫组织化学方法检测各组织标本Wnt3、β-catenin、MMP-7的表达。结果: Wnt3、β-catenin、MMP-7在胃癌组和癌前病变组均呈高表达，Wnt3、MMP-7高表达于细胞质，β-catenin呈细胞膜向细胞质及细胞核转移的趋势，表现为“核易位”特点。胃癌组Wnt3、β-catenin、MMP-7表达的阳性率高于癌前病变组和慢性浅表性胃炎组，且随分化程度的恶化，呈逐步升高趋势，差异均有统计学意义(均 P<0.05)；同时，Wnt3、β-catenin、MMP-7在胃癌组和癌前病变组的Hp阳性亚组中的表达均明显高于Hp阴性亚组，差异均有统计学意义(均P<0.05)。结论: Wnt信号通路的异常激活参与了胃癌前病变以及胃癌的发生、发展，并与Hp感染密切相关。同时，Wnt3、β-catenin和MMP-7有可能成为胃癌早期诊断的分子标志物及判断胃癌恶性程度的指标。.

Keywords: Helicobacter pylori; Wnt signal pathway; Wnt3; gastric cancer; immunohistochemical method; precancerous lesions.

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Conflict of interest statement

作者声称无任何利益冲突。

Figures

图1
图1
慢性浅表性胃炎组、胃癌组及癌前病变组Wnt3的表达(免疫组化染色，×100) Figure 1 Expression of Wnt3 in the chronic superficial gastritis group, the gastric cancer group, and the precancerous lesion group (immunohistochemistry staining, ×100) A: Expression of Wnt3 in the chronic superficial gastritis group; B: Expression of Wnt3 in poorly differentiated adenocarcinoma in the gastric cancer group; C: Expression of Wnt3 in moderately differentiated adenocarcinoma in the gastric cancer group; D: Expression of Wnt3 in well differentiated adenocarcinoma in the gastric cancer group; E: Expression of Wnt3 in the atypical hyperplasia in the precancerous lesion group; F: Expression of Wnt3 in the gastric intestinal metaplasia in the precancerous lesion group.
图2
图2
慢性浅表性胃炎组、胃癌组及癌前病变组MMP-7的表达(免疫组化染色，×100) Figure 2 Expression of MMP-7 in the chronic superficial gastritis group, the gastric cancer group and the precancerous lesion group (immunohistochemistry staining, ×100) A: Expression of MMP-7 in the chronic superficial gastritis group; B: Expression of MMP-7 in the poorly differentiated adenocarcinoma in the gastric cancer group; C: Expression of MMP-7 in moderately differentiated adenocarcinoma in the gastric cancer group; D: Expression of MMP-7 in well differentiated adenocarcinoma in the gastric cancer group; E: Expression of MMP-7 in the atypical hyperplasia in the precancerous lesion group; F: Expression of MMP-7 in gastric intestinal metaplasia in the precancerous lesion group.
图3
图3
慢性浅表性胃炎组、胃癌组及癌前病变组β-catenin的表达(A~F：免疫组化染色，×100；a~f：免疫组化染色，×200) Figure 3 Expression of β-catenin in the chronic superficial gastritis group, the gastric cancer group, and the precancerous lesion group (A-F: Immunohistochemistry staining, ×100; a-f: Immunohistochemistry staining, ×200) A-F: Expression of β-catenin in the chronic superficial gastritis group (A), the poorly differentiated adenocarcinoma in the gastric cancer group (B), the moderately differentiated adenocarcinoma in the gastric cancer group (C), the well differentiated adenocarcinoma in the gastric cancer group (D), the atypical hyperplasia in the precancerous lesion group (E) and the gastric intestinal metaplasia in the precancerous lesion group (F); a-f: Local amplification is respectively corresponded to the black frame of A-F, which shows that β-catenin has tendency of transferring from cell membrane to cytoplasm and nucleus in the chronic superficial gastritis group, the gastric cancer group and the precancerous lesion group.
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