Wang Wei, Luo He-Sheng, Yu Bao-Ping
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
World J Gastroenterol. 2004 Jan 15;10(2):177-81. doi: 10.3748/wjg.v10.i2.177.
To investigate the expression of NF-kappaBp65 protein and human telomerase reverse transcriptase (hTERT) and their correlation in gastric cancer and precancerous lesions.
Forty-one patients with primary gastric cancer, 15 with dysplasia, 23 intestinal metaplasia and 10 with normal gastric mucosa were included in this study. Expression of NF-kappaBp65 protein, hTERT mRNA and protein were determined by immunohistochemistry and in situ hybridization.
The rate of p65 expression in normal gastric mucosa, intestinal metaplasia, dysplasia and carcinoma was 0%, 34.78%, 53.33% and 60.98%, respectively, while the rate of hTERT mRNA expression was 10.00%, 39.13%, 66.67% and 85.37% and the rate of hTERT protein expression was 0%, 30.43%, 60.00% and 78.05%, respectively. All the three parameters were significantly increased in dysplasia and carcinoma compared to normal mucosa, while the expression levels were also significantly higher in carcinoma than in intestinal metaplasia (P<0.05). In gastric cancer tissues, nuclear staining rates of p65 and hTERT protein were both significantly associated with the degree of differentiation, lymph node metastasis, clinical stage and invasion depth (P<0.05). However, hTERT mRNA expression was only significantly associated with clinical stage. There was a positive correlation between p65 and hTERT mRNA (rs=0.661-0.752, P<0.01), and between hTERT protein and hTERT mRNA (rs=0.609-0.750, P<0.01).
NF-kappaBp65 and hTERT expressions are upregulated at the early stage of gastric carcinogenesis. NF-kappaB activation may contribute to hTERT expression and thereby enhance telomerase activity, which represents an important step in carcinogenesis progress.
研究核因子-κB p65蛋白（NF-κBp65）和人端粒酶逆转录酶（hTERT）在胃癌及癌前病变中的表达及其相关性。
本研究纳入41例原发性胃癌患者、15例发育异常患者、23例肠化生患者及10例正常胃黏膜患者。采用免疫组织化学和原位杂交法检测NF-κBp65蛋白、hTERT mRNA及蛋白的表达。
正常胃黏膜、肠化生、发育异常及癌组织中p65的表达率分别为0%、34.78%、53.33%和60.98%，hTERT mRNA的表达率分别为10.00%、39.13%、66.67%和85.37%，hTERT蛋白的表达率分别为0%、30.43%、60.00%和78.05%。与正常黏膜相比，发育异常和癌组织中这三个参数均显著升高，且癌组织中的表达水平也显著高于肠化生（P<0.05）。在胃癌组织中，p65和hTERT蛋白的核染色率均与分化程度、淋巴结转移、临床分期及浸润深度显著相关（P<0.05）。然而，hTERT mRNA表达仅与临床分期显著相关。p65与hTERT mRNA之间呈正相关（rs=0.6610.752，P<0.01），hTERT蛋白与hTERT mRNA之间也呈正相关（rs=0.6090.750，P<0.01）。
NF-κBp65和hTERT的表达在胃癌发生的早期阶段上调。NF-κB激活可能有助于hTERT表达，从而增强端粒酶活性，这是致癌进程中的重要一步。
