Expression of the ERBB Family of Ligands and Receptors in Gastric Cancer
Expression of the ERBB Family of Ligands and Receptors in Gastric Cancer
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DOI：
10.1159/000464250
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发表时间：
2017-01-01
期刊：
影响因子：
5
通讯作者：
Kim, Woo Ho
中科院分区：
文献类型：
--
作者：
Byeon, Sun-ju;Lee, Hye Seung;Kim, Woo Ho
目的：胃癌(GC)是韩国第二大常见癌症和第三大癌症相关死亡原因。ERBB(与红母细胞瘤病毒基因产物同源，v-erbB)受体家族和ERBB相关信号通路的改变在GC中非常常见。然而，ERBB受体及其配体在GC中的作用尚不清楚。方法：采用免疫组织化学、荧光原位杂交和mRNA原位杂交技术，检测313例胃癌组织中不同受体配体(即肝素结合的表皮生长因子样生长因子[HBEGF]、转化生长因子-α[TGFA]、两用调节素[AREG]、表皮调节蛋白[Ereg]、表皮生长因子[EGF]和β细胞蛋白[BTC])和3种ERBB家族受体(即表皮生长因子受体[EGFR]、人EGFR2[HER2]和ERBB3)的表达水平。结果：EGFR高表达30例，HER2高表达32例，ERBB3高表达27例。HBEGF、TGFA、AREG、Ereg、EGF和BTC的高表达分别为91、97、151、74、26和37例。TGFA的高表达与较好的生存相关，而BTC的高表达与较差的生存相关。这些结果通过COX比例风险分析得到了证实。多因素分析显示HBEGF、TGFA、AREG、肿瘤-淋巴结转移分级、Lauren分级和ERBB3是有意义的生存参数。结论：在所检测的ERBB家族受体和配体中，有3种配体(即TGFA、HBEGF和AREG)和ERBB3对预后有影响。(C)2017年S.Karger AG，巴塞尔
Objective: Gastric cancer (GC) is the second most common cancer and the third leading cause of cancer-related death in Korea. Alterations in the ERBB (homology to the erythroblastoma viral gene product, v-erbB) receptor family and ERBB-related signaling pathways are frequently observed in GC. However, the roles of the ERBB receptors and their ligands in GC are not well established. Methods: We evaluated the expression levels of various ERBB receptor ligands (i.e., heparin-binding epidermal growth factor-like growth factor [HBEGF], transforming growth factor-a [TGFA], amphiregulin [AREG], epiregulin [EREG], epidermal growth factor [EGF], and betacellulin [BTC]) and 3 ERBB family receptors (i.e., epidermal growth factor receptor [EGFR], human EGFR2 [HER2], and ERBB3) in 313 cases of GC using immunohistochemistry, fluorescence in situ hybridization, and mRNA in situ hybridization. Results: A high expression of EGFR, HER2, and ERBB3 was observed in 30, 32, and 27 cases, respectively. A high expression of HBEGF, TGFA, AREG, EREG, EGF, and BTC was observed in 91, 97, 151, 74, 26, and 37 cases, respectively. A high expression of TGFA was associated with better survival, while a high expression of BTC was associated with worse survival. These results were confirmed using Cox proportional hazards analysis. HBEGF, TGFA, AREG, tumor-nodemetastasis classification, Lauren's classification, and ERBB3 were significant survival parameters in multivariate analysis. Conclusion: Among the ERBB family receptors and ligands examined, 3 ligands (i.e., TGFA, HBEGF, and AREG) and ERBB3 had a prognostic impact. (C) 2017 S. Karger AG, Basel