期刊
LUNG CANCER
卷 122, 期 -, 页码 131-137出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2018.06.005
关键词
Endoplasmic reticulum stress; GRP78; Non-small cell lung cancer; Unfolded protein response; XBP1 spliced form
资金
- Collaborative Research Program of SNU Boramae Medical Center and Basic Medical Science from Seoul National University College of Medicine [800-20160023]
- Seoul National University Hospital Research Fund [0320170410 [2017-1344]]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI14C1277]
Objectives: Endoplasmic reticulum (ER) stress is associated with tumor development and progression via pro-tumorigenic and anti-tumorigenic effects. However, the clinicopathological implications of the ER stress pathway in non-small cell lung cancer remain unclear. Therefore, we sought to address these issues in this study. Materials and methods: Expression of two ER stress-related proteins, GRP78 and XBP1 spliced-form (XBP1s), was evaluated in pulmonary adenocarcinoma (pADC; n = 369) and squamous cell carcinoma (pSqCC; n = 246) using immunohistochemistry. Results: Expression levels of GRP78 and XBP1s were significantly higher in pADCs and pSqCCs, respectively (both, P < 0.0001). In the pADC group, XBP1s expression was higher in patients with ALK translocation than in those with wild-type ALK, wild-type EGFR, or EGFR mutation (P < 0.005). No significant difference in GRP78 expression according to ALK or EGFR status was noted. pADC harboring high GRP78 expression exhibited an increased XBP1s expression (P = 0.0067). Higher XBP1s expression was associated with shorter disease-free survival (DFS) in patients with pADC (P = 0.026) and in those with ALK translocation (P = 0.001). Higher GRP78 expression was associated with shorter DFS in patients with pADC (P = 0.029) and those with EGFR mutation (P = 0.005). Multivariate survival analysis revealed that high XBP1s expression was an independent predictor of poor DFS in pADC (P = 0.004, hazard ratio [HR] = 3.115), and that high GRP78 expression was an independent predictor of poor DFS in EGFR-mutated pADC (P = 0.007, HR = 2.168). Taken together, high expression of XBP1s or GRP78 was an independent poor prognostic factor in pADC (P = 0.002, HR = 2.403). Conclusion: GRP78 and XBP1s are expressed variably in pADC, but their overexpression is associated with poor patient prognosis. The ER stress pathway may be a prognostic biomarker and potential therapeutic target for pADC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据