COL4A3 expression correlates with pathogenesis, pathologic behaviors, and prognosis of gastric carcinomas
COL4A3 expression correlates with pathogenesis, pathologic behaviors, and prognosis of gastric carcinomas
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COL4A3表达与胃癌的发病机制、病理行为和预后相关
DOI：
10.1016/j.humpath.2011.10.028
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发表时间：
2013-01-01
期刊：
影响因子：
3.3
通讯作者：
Zheng, Hua-chuan
中科院分区：
文献类型：
--
作者：
Nie, Xiao-cui;Wang, Jian-Ping;Zheng, Hua-chuan
Col4A3蛋白属于IV型胶原家族，与肾脏疾病和癌症密切相关。为了阐明Col4A3在胃癌发生和发展中的作用，采用免疫组织化学方法检测了Col4A3在胃癌、癌旁肠化生、单纯肠化生和胃炎组织芯片中的表达。用Western blotting和逆转录聚合酶链式反应检测胃癌组织和细胞系中Col4A3的表达。我们发现Col4A3在GES-1、AGS、BGC-823、GT-3 TKB、HGC-27、Kato-III、MGC-803、MKN28、MKN45、Sch、SGC-7901和STKM-2的信使RNA和蛋白质水平上均有差异表达。癌组织中Col4A3的表达显著低于非肿瘤性组织(P<；0.05)。肠上皮化生的表达强于胃炎和癌(P<；0.05)。COL4A3在胃癌中的表达高于胃炎(P<；0.05)。COL4A3蛋白的表达与肿瘤大小、淋巴侵犯、静脉侵犯和TNM分期呈正相关(P<；0.05)。无论是否侵犯固有肌层，弥漫型癌中Col4A3的表达均高于肠型癌(P<；0.05)。所有印戒细胞癌(43例)和粘液性癌(12例)均表达Col4A3。Kaplan-Meier分析显示，Col4A3的表达与进展期和肠型胃癌的预后呈负相关(P<；0.05)。Col4A3的异常表达可能在胃癌的发生、发展中起重要作用。Col4A3过表达可作为胃肠化生和粘液印戒细胞癌的标志物。Crown版权所有(C)2013由Elsevier Inc.出版。保留所有权利。
COL4A3 protein belongs to type IV collagen family and is closely linked to kidney diseases and cancer. To clarify the roles of COL4A3 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry on tissue microarrays containing gastric carcinomas, adjacent intestinal metaplasia, pure intestinal metaplasia, and gastritis. Gastric carcinoma tissue and cell lines were studied for COL4A3 expression by Western blotting and reverse transcription polymerase chain reaction. We found that COL4A3 was differentially expressed in GES-1, AGS, BGC-823, GT-3 TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, and STKM-2 at both messenger RNA and protein levels. Carcinomas showed statistically lower COL4A3 expression than matched nonneoplastic mucosa (P < .05). Expression was strong in intestinal metaplasia in comparison with gastritis and carcinoma (P < .05). There was greater COL4A3 expression in carcinoma than gastritis (P < .05). Expression of COL4A3 protein was positively correlated with tumor size, lymphatic invasion, venous invasion, and TNM stage (P < .05). There was more COL4A3 expression in diffuse than in intestinal-type carcinomas regardless of invasion into the muscularis propria (P < .05). Histologically, all signet ring cell (n = 43) and mucinous (n = 12) carcinomas showed COL4A3 expression. Kaplan-Meier analysis indicated that COL4A3 expression was negatively associated with a favorable prognosis of overall, advanced, and intestinal-type gastric carcinomas (P < .05). Aberrant COL4A3 expression might play an important role in the pathogenesis and subsequent progression of gastric carcinoma. COL4A3 overexpression might be used as a marker of gastric intestinal metaplasia and mucinous and signet ring cell carcinoma. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.