Expression of glucose regulated protein 78 (GRP78) determines colorectal cancer response to chemotherapy
Expression of glucose regulated protein 78 (GRP78) determines colorectal cancer response to chemotherapy
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DOI：
10.3233/cbm-140454
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发表时间：
2015-01-01
影响因子：
3.1
通讯作者：
Khabour, Omar F.
中科院分区：
文献类型：
--
作者：
Mhaidat, Nizar M.;Alzoubi, Karem H.;Khabour, Omar F.
背景：结直肠癌（Colorectal cancer，CRC）是一个世界性的重要健康问题.在CRC的筛查和早期发现方面取得了很大的进步。然而，一个新的分子预后标志物在很大程度上是必需的。葡萄糖调节蛋白78-kDa（glucose regulated protein 78-kDa，GRP 78）是内质网（endoplasmic reticulum，ER）的核心调节因子，在肿瘤细胞增殖、分化和化疗耐药中起重要作用。收集68例结直肠癌组织样本，并使用免疫组织化学评估GRP 78的蛋白表达。结果：GRP 78在大肠癌组织中的表达随临床分期的增加而增加，随着临床分期的增加，GRP 78的表达逐渐增强。此外，GRP 78水平随着肿瘤定位从早期T1-2到晚期T3-4的进展而增加（p < 0.05）。此外，GRP 78表达与化疗反应之间存在显著相关性（p < 0.05）。GRP 78表达和患者的临床特征，包括淋巴结受累和转移之间的关联是不显着的。结论：结果表明，使用GRP 78作为CRC进展的生物标志物和其化疗敏感性治疗的可能性。
BACKGROUND: Colorectal cancer (CRC) is an important health problem all over the world. A great improvement in the screening and early detection of CRC has been achieved. However, a new molecular prognostic marker is largely required. Glucose regulated protein 78-kDa (GRP78) is the central regulator of the endoplasmic reticulum (ER) and has an important role in the proliferation, differentiation and resistance to chemotherapy in cancer cells.OBJECTIVE: The aim of the present study was to investigate the impact of elevated level of GRP78 on CRC prognosis and chemosensitivity.METHODS: Sixty eight CRC tissue samples were collected and protein expression of GRP78 was evaluated using immunohistochemistry. The clinicopathological factors of the patients were correlated with GRP78 level.RESULTS: GRP78 expression increased with the progression from early to advanced CRC stages. In addition, GRP78 level was increased with the progression from early T1-2 to late T3-4 tumor localization (p < 0.05). Moreover, a significant association was found between GRP78 expression and response to chemotherapy (p < 0.05). Association between GRP78 expression and patient's clinical characteristics including lymph node involvement and metastasis was not significant.CONCLUSIONS: Results suggest the possibility to use GRP78 as a biomarker for progression of CRC and its chemosensitivity to therapy.