胃腺体组织癌变过程中CD44和survivin表达与幽门螺杆菌感染的相关性及其在胃癌浸润和转移中的作用

Relationship between CD44,survivin expression and Helicobacter pylori infection in gastric gland tissue carcinogenesis and their role in infiltration and metastasis of gastric cancer

目的分析胃腺体组织癌变过程中CD44、survivin表达与幽门螺杆菌(HP)感染的相关性,探讨CD44、survivin在胃腺体组织癌变过程及胃癌(GC)浸润和转移中的作用。方法选择2022年4月至2022年6月于新疆医科大学附属肿瘤医院就诊的资料完整且为首次经胃镜及病理学检查后确诊慢性非萎缩性胃炎(CNAG)患者(CNAG组)、慢性萎缩性胃炎(CAG)患者(CAG组)、肠上皮化生(IM)患者(IM组)、异型增生(AH)患者(AH组)和GC患者(GC组)各50例为研究对象,收集各组患者的胃黏膜病变组织。采用快速尿素酶和碳14法分别检测CNAG、CAG、IM、AH和GC患者胃黏膜病变组织中HP感染情况,苏木精-伊红染色观察不同患者胃黏膜病变组织形态,免疫组织化学法检测不同患者胃黏膜病变组织中CD44和survivin的蛋白表达水平,实时荧光定量聚合酶链反应检测不同患者胃黏膜病变组织中CD44和survivin mRNA表达。结果250例患者中,HP感染率为50.4%(126/250),其中CNAG、CAG、IM、AH和GC患者的HP感染率分别为10.0%(5/50)、24.0%(12/50)、44.0%(22/50)、68.0%(34/50)、80.0%(40/50),HP感染率呈显著增高趋势(χ^(2)=68.068,P<0.001)。CNAG组、CAG组、IM组、AH组和GC组患者胃黏膜病变组织中CD44蛋白阳性表达率分别为4.0%、16.0%、32.0%、62.0%、80.0%,呈逐渐升高趋势(χ^(2)=84.50,P<0.001)。CAG组、IM组、AH组和GC组胃黏膜病变组织中survivin蛋白阳性表达率分别为18.0%、38.0%、58.0%、68.0%,呈逐渐升高趋势(χ^(2)=67.63,P<0.001)。CAG组、IM组、AH组和GC组患者胃黏膜病变组织中CD44和survivin mRNA相对表达量显著高于CNAG组,IM组、AH组和GC组患者胃黏膜病变组织中CD44和survivin mRNA相对表达量显著高于CAG组,AH组和GC组患者胃黏膜病变组织中CD44和survivin mRNA相对表达量显著高于IM组,GC组患者胃黏膜病变组织中CD44和survivin mRNA相对表达量显著高于AH组(P<0.001)。CAG组、IM组、AH和GC组HP阳性患者胃黏膜组织中CD44、survivin蛋白阳性表达率显著高于阴性患者(P<0.01)。CNAG组HP阳性患者与阴性患者胃黏膜组织中CD44、survivin蛋白阳性表达率比较差异无统计学意义(P>0.05)。CD44和survivin蛋白表达与GC患者癌组织分化程度、淋巴结转移、远处转移相关(P<0.05),CD44和survivin蛋白表达与GC患者的浸润深度无相关性(P>0.05)。结论HP感染与CD44和survivin基因表达间存在正关联,胃腺体组织癌变过程中Hp感染可能诱导CD44和survivin基因表达,从而通过改变黏膜细胞的生物学活性来发挥促癌作用;CD44和survivin可促进GC的浸润和转移。

Objective To analyze the correlation between the expressions of CD44 and survivin and Helicobacter pylori(HP)infection during the carcinogenesis process of gastric gland tissue,and explore the role of CD44 and survivin in the carcinogenesis process of gastric gland tissue and infiltration and metastasis of gastric cancer(GC).Methods The 50 cases of chronic non-atrophic gastritis(CNAG)patients(CNAG group),50 cases of chronic atrophic gastritis(CAG)patients(CAG group),50 cases of intestinal metaplasia(IM)patients(IM group),50 cases of atypical hyperplasin(AH)patients(AH group)and 50 GC patients(GC group)diagnosed by gastroscopy and pathology for the first time with complete data admitted to Cancer Hospital Affiliated to Xinjiang Medical University from April to June 2022 were selected as the rearch subieets,and the gastric mucosa lesions of the patients in each group were collected.The HP infection in gastric mucosa pathological tissues of CNAG,CAG,IM,AH and GC patients was detected by rapid urease and C-14 methods,respectively.The morphology of gastric mucosa lesions of different patients was observed by hematoxylin-eosin staining.The expressions of CD44 and survivin protein in gastric mucosa lesions of different patients were detected by immunohistochemical method.The expressions of CD44 and survivin mRNA in gastric mucosa lesions of different patients were detected by real-time fluorescence quantitative polymerase chain reaction.Results Among the 250 patients,the HP infection rate was 50.4%(126/250),and the HP infection rate of CNAG,CAG,IM,AH,and GC patients were 10.0%(5/50),24.0%(12/50),44.0%(22/50),68.0%(34/50),and 80.0%(40/50),respectively;the HP infection rate showed a significant increase trend(χ^(2)=68.068,P<0.001).The positive expression rates of CD44 protein in gastric mucosa lesions of patients in the CNAG group,CAG group,IM group,AH group and GC group were 4.0%,16.0%,32.0%,62.0%and 80.0%,respectively,which showed a gradually increasing trend(χ^(2)=84.500,P<0.001).The positive expression rates of survivin protein in gastric mucosa lesions of patients in the CAG group,IM group,AH group and GC group were 18.0%,38.0%,58.0%and 68.0%,respectively,which showed a gradually increasing trend(χ^(2)=67.630,P<0.001).The relative expression levels of CD44 and survivin mRNA in gastric mucosa lesions of patients in the CAG group,IM group,AH group and GC group were significantly higher than those in the CNAG group(P<0.001);the relative expression levels of CD44 and survivin mRNA in gastric mucosa lesions of patients in the IM group,AH group and GC group were significantly higher than those in the CAG group(P<0.001);the relative expression levels of CD44 and survivin mRNA in gastric mucosa lesions of patients in the AH group and GC group were significantly higher than those in the IM group(P<0.001);the relative expression levels of CD44 and survivin mRNA in gastric mucosa lesions of patients in the GC group were significantly higher than those in the AH group(P<0.001).The positive expression rates of CD44 and survivin protein in gastric mucosa of HP positive patients was significantly higher than those of HP negative patients in the CAG group,IM group,AH group and GC group(P<0.01).There was no significant difference in the positive expression rates of CD44 and survivin protein in gastric mucosa between HP positive patients and negative patients in the CNAG group(P>0.05).The expressions of CD44 and survivin was correlated with the degree of cancer tissue differentiation,lymph node metastasis and distant metastasis in GC patients(P<0.05);while the expressions of CD44 and survivin protein was not correlated with the depth of infiltration in GC patients(P>0.05).Conclusion There is a positive correlation between HP infection and the expression of CD44 and survivin gene.During the carcinogenesis process of gastric gland tissue,Hp infection may induce the expression of CD44 and survivin gene,thereby exerting a tumor-promoting effect by altering the biological activity of mucosal cells;CD44 and survivin can promote the infiltration and metastasis of GC.