CagA^+幽门螺杆菌胃癌前及癌变中NF-κB的表达增强

Increased expression of NF-κB p65 in CagA^+ H pylori-related gastric precancerous lesions and carcinoma

目的:探讨核因子-κB(nuclearfactor-KappaB,NF-κB)在癌前病变及胃癌组织中的表达及其与细胞毒素相关抗原A幽门螺杆菌(CagA+Hpylori)感染之间的关系.方法:慢性浅表性胃炎34例,肠腺化生31例,不典型增生34例,胃癌55例,应用免疫组化方法(SABC法)检测NF-κBp65的表达,以14C-呼气试验、快速尿素酶试验和Warthin-Starry银染色检测Hpylori,采用斑点金免疫渗滤法检测患者血清抗HpyloriCagAIgG抗体,分析NF-κBp65表达与CagA+Hpylori感染之间、以及与胃癌组织学分型、临床病理分期、淋巴结转移的关系.结果:在慢性浅表性胃炎、肠腺化生、不典型增生和胃癌组中,NF-κBp65阳性表达率分别为15.0%,41.9%,64.7%和78.2%,呈逐渐增高趋势,各组间有显著性差异(χ2=43.98,P<0.01);Hpylori感染率分别为70.0%,67.7%,73.5%和54.5%,各组间无显著性差异(P>0.05).CagA+Hpylori构成比分别为53.6%,61.9%,68.0%和73.3%,各组间无显著性差异(P>0.05).在肠化组中,Hpylori阳性和CagA+Hpylori感染的患者NF-κBp65阳性表达率分别为57.1%和76.9%,显著高于同组无Hpylori感染的10.0%(χ2=6.18,P<0.05)和CagA-Hpylori感染者的25.0%(χ2=5.45,P<0.05).在胃癌组中,NF-κBp65阳性表达与T分期(χ2=5.91,P<0.05)及淋巴结转移有关(χ2=7.47,P<0.05),但与胃癌组织学分型无关(P>0.05).结论:NF-κB的异常活化在胃癌前病变及癌变过程中起作用,早期的活化与CagA+Hpylori感染有关.

AIM： To determine the expression of nuclear factor kappa B （NF-κB） in human gastric precancerous lesions and carcinoma and its correlation with CagA^＋ H pylori infection. METHODS： The expression of NF-κB p65 was detected by immunohistochemistry （SABC assay）, and H py/ori were examined using 14C-breath test, rapid urease test and Warthin-Starry staining in patients with chronic superficial gastritis （CSG：n = 34）, intestinal metaplasia （IM： n = 31）, atypical dysplasia （AD：n = 34） and gastric cancer （GC：n = 55）. Serum CagA IgG antibody was detected by dot immunogold filtration assay. The correlations of NF-κB p65 expression with CagA^＋ H pylori infection as well as the histological types, clinicopathological stages and lymph node metastasis were analyzed. RESULTS： The expression of NF-κB p65 in CSG, IM, AD, GC was 15.0%, 41.9%, 64.7%, and 78.2%, respectively, and there were significant differences between them （7.2 = 43.98, P 〈0.01）. The rates of H pylori infection were 70.0%, 67.7%, 73.5%, and 54.5%, respectively, and there were no significant differences between them （P 〉0.05）. The percentage of CagA^＋ Hpylori infection were 53.6%, 61.9%, 68.0%, and 73.3%, respectively, and there were no significant differences （P 〉0.05）. In IM, the positive rate of NF-κB p65 expression in Hpylori or CagA^＋ H pylori positive patients were significantly higher than that in patients without Hpylori infection or with CagA H pylori infection （57.1%, 76.9% vs 10%, 25.0%, P 〈0.05）. In GC patients, the positive expression of NF-κB p65 was correlation with the T stages（7.2 = 5.91, P 〈0.05） and lymph node metastasis （7.2 = 7.47, P 〈0.01）, but not with the pathohistological types （P 〉0.05）. CONCLUSION： NF-κB is constitutively activated in human gastric precancerous lesions and carcinoma tissue and correlates with tumor progression. The early activation may be related to CagA＋ H pylori infection.