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ING5 蛋白表达的改变与胃癌的发生和随后的进展有关。

The altered expression of ING5 protein is involved in gastric carcinogenesis and subsequent progression.

机构信息

Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 110001, China.

出版信息

Hum Pathol. 2011 Jan;42(1):25-35. doi: 10.1016/j.humpath.2010.05.024. Epub 2010 Nov 9.

DOI:10.1016/j.humpath.2010.05.024
PMID:21062663
Abstract

ING5 can interact with p53, thereby inhibiting cell growth and inducing apoptosis. To clarify the roles of ING5 in gastric tumorigenesis and progression, its expression was examined by immunohistochemistry on a tissue microarray containing gastric nonneoplastic mucosa (n = 119), dysplasia (n = 50), and carcinomas (n = 429), with its comparison with clinicopathologic parameters of the carcinomas. ING5 expression was analyzed in gastric carcinoma tissues and cell lines (MKN28, MKN45, AGS, GT-3 TKB, and KATO-III) by Western blot and reverse transcriptase-polymerase chain reaction. ING5 protein was found to distribute to the nuclei of gastric carcinoma cells with similar messenger RNA levels. An increased expression of ING5 messenger RNA was observed in gastric carcinoma in comparison with paired mucosa (P < .05). Lower expression of nuclear ING5 was detected in gastric dysplasia and carcinoma than that in nonneoplastic mucosa (P < .05). Gastric nonneoplastic mucosa and metastatic carcinoma showed more expression of cytoplasmic ING5 than did gastric carcinoma and dysplasia (P < .05). Nuclear ING5 expression was negatively correlated with tumor size, depth of invasion, lymph node metastasis, and clinicopathologic staging (P < .05), whereas cytoplasmic ING5 was positively associated with depth of invasion, venous invasion, lymph node metastasis, and clinicopathologic staging (P < .05). Nuclear ING5 was more expressed in older than younger carcinoma patients (P < .05). There was a higher expression of nuclear ING5 in intestinal-type than diffuse-type carcinoma (P < .05), whereas it was the converse for cytoplasmic ING5 (P < .05). Survival analysis indicated that nuclear ING5 was closely linked to favorable prognosis of carcinoma patients (P < .05), albeit not independent. It was suggested that aberrant ING5 expression may contribute to pathogenesis, growth, and invasion of gastric carcinomas and could be considered as a promising marker to gauge aggressiveness and prognosis of gastric carcinoma.

摘要

ING5 可以与 p53 相互作用,从而抑制细胞生长并诱导细胞凋亡。为了阐明 ING5 在胃癌发生和进展中的作用,我们通过免疫组织化学方法在包含胃非肿瘤性黏膜(n=119)、异型增生(n=50)和癌(n=429)的组织微阵列上检查了 ING5 的表达,并将其与癌的临床病理参数进行了比较。通过 Western blot 和逆转录聚合酶链反应分析了 ING5 在胃癌组织和细胞系(MKN28、MKN45、AGS、GT-3 TKB 和 KATO-III)中的表达。发现 ING5 蛋白分布在胃癌细胞的核内,信使 RNA 水平相似。与配对黏膜相比,胃癌中 ING5 信使 RNA 的表达增加(P<0.05)。与非肿瘤性黏膜相比,胃异型增生和癌中核 ING5 的表达降低(P<0.05)。胃非肿瘤性黏膜和转移性癌的细胞质 ING5 表达高于胃癌和异型增生(P<0.05)。核 ING5 表达与肿瘤大小、浸润深度、淋巴结转移和临床病理分期呈负相关(P<0.05),而细胞质 ING5 与浸润深度、静脉侵犯、淋巴结转移和临床病理分期呈正相关(P<0.05)。核 ING5 在老年患者中的表达高于年轻患者(P<0.05)。肠型癌中核 ING5 的表达高于弥漫型癌(P<0.05),而细胞质 ING5 的表达则相反(P<0.05)。生存分析表明,核 ING5 与癌患者的良好预后密切相关(P<0.05),尽管不是独立的。提示异常 ING5 表达可能有助于胃癌的发病机制、生长和侵袭,可作为评估胃癌侵袭性和预后的有前途的标志物。

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