Prognostic role of BiP/GRP78 expression as ER stress in patients with gastric adenocarcinoma
Prognostic role of BiP/GRP78 expression as ER stress in patients with gastric adenocarcinoma
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DOI：
10.3233/cbm-170062
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发表时间：
2017-01-01
影响因子：
3.1
通讯作者：
Oyama, Tetsunari
中科院分区：
文献类型：
--
作者：
Ogawa, Hiroomi;Kaira, Kyoichi;Oyama, Tetsunari
目的：葡萄糖调节蛋白78(GRP78)又称免疫球蛋白重链结合蛋白(Bip/GRP78)，是内质网(ER)的主要分子伴侣，在人类肿瘤中广泛表达。虽然Bip/GRP78的高表达被认为与胃癌的预后不良有关，但关于其预后意义的细节仍不清楚。本研究的目的是阐明Bip/GRP78基因的表达对肿瘤患者预后的影响。方法：研究对象为328例手术切除患者。结果：BIP/GRP78高表达者占57%(188/328)。Bip/GRP78的高表达与年龄、男性、疾病分期、T因子、淋巴结转移、分化程度、淋巴渗透和血管侵犯显著相关。单因素分析显示，年龄、疾病分期、T因子、N因子、淋巴渗透、血管侵犯、Bip/GRP78表达是影响OS预后的重要因素。结论：Bip/GRP78的高表达与肿瘤的侵袭性和侵袭性密切相关。Bip/GRP78的高表达是预测早期患者OS不良的独立因素，尤其是T1-2因素。
PURPOSE: The glucose-regulated protein 78 (GRP78), also referred to as immunoglobulin heavy chain binding protein (BiP) (BiP/GRP78), is a major molecular chaperone in the endoplasmic reticulum (ER) and is extensively expressed in human neoplasms. Although the enhanced expression of BiP/GRP78 has been described to be associated with poor prognosis in gastric cancer (GC), details regarding its prognostic significance remain unclear. The aim of this study was to elucidate the prognostic role of BiP/GRP78 in patients with GC.METHODS: Study subjects included 328 patients who underwent surgical resection. Tumor specimens of primary tumors underwent immunohistochemical staining for BiP/GRP78.RESULTS: BiP/GRP78 was highly expressed in 57% (188/328) of patients. High expression of BiP/GRP78 was significantly associated with older age, male, disease staging, T factor, lymph node metastases, differentiation, lymphatic permeation, and vascular invasion. According to univariate analysis, age, disease staging, T factor, N factor, lymphatic permeation, vascular invasion, and BiP/GRP78 expression were significant prognostic factors for OS. In particular, high BiP/GRP78 expression was proven to be a significant predictor of prognosis in patients with older age, female sex, early disease stage, T1-2 factor, well or moderately differentiated tumors, and negative vascular invasion.CONCLUSION: BiP/GRP78 is significantly associated with tumor aggressiveness and progression. The increased expression of BiP/GRP78 was identified as an independent factor for predicting poor OS in patients with early stage of disease, especially T1-2 factor.