Prognostic significance of G6PD expression and localization in lung adenocarcinoma
Prognostic significance of G6PD expression and localization in lung adenocarcinoma
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DOI：
10.1016/j.bbapap.2018.05.005
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发表时间：
2019-01-01
影响因子：
3.2
通讯作者：
Sato, Yuichi
中科院分区：
文献类型：
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作者：
Nagashio, Ryo;Oikawa, Shota;Sato, Yuichi
细胞外基质（ECM）蛋白的异常表达与肿瘤进展加快、组织学分级和转移有关。从肺大细胞神经内分泌癌中提取的LCN1细胞在悬浮培养皿中培养形成aegagropila形状的团块（LCN1-sus）。相比之下，在I型胶原培养皿中培养的LCN1细胞是贴壁的，并且倾向于生长为纺锤形的单个细胞（LCN1-co）。在本研究中，为了发现肿瘤侵袭的预测标志物，我们使用二维凝胶电泳技术对LCN1-sus和LCN1-co细胞进行了蛋白谱分析。在LCN1-sus和LCN1-co细胞中检测到26个蛋白点，其数量差异为bb0的1.2倍。在已鉴定的蛋白中，我们重点研究了G6PD在肺癌中的作用，并进行了免疫组化研究。G6PD表达与腺癌较高的病理TNM分期（p = 0.0024）、淋巴结转移（p = 0.0187）、较差的分化（p = 0.0046）、胸膜浸润（p = 0.0197）、血管浸润（p < 0.0001）、淋巴浸润（p = 0.0200）和较差的预后（p = 0.0005）显著相关。特别是侵袭前过表达的g6pd阳性患者的生存期明显低于未过表达的患者（p = 0.0058）。此外，多变量分析显示G6PD表达是一个独立的不良预后因素。这些结果提示G6PD可能是一种新的肺腺癌预后预测指标。
Abnormal expressions of extracellular matrix (ECM) proteins are correlated with increased tumor progression, an advanced histologic grade, and metastasis. LCN1 cells derived from a pulmonary large cell neuroendocrine carcinoma were grown to form an Aegagropila-shaped conglomeration on a suspension culture dish (LCN1-sus). In contrast, LCN1 cells cultured in a type I collagen dish were adherent and tended to grow as spindle-shaped individual cells (LCN1-co). In this study, aiming at the discovery of predictive markers for tumor invasion, we performed protein profiling between LCN1-sus and LCN1-co cells using two-dimensional gel electrophoresis. Twenty-six protein spots with > 1.2-fold quantitative differences between LCN1-sus and LCN1-co cells were detected. Among the identified proteins, we focused on and immunohistochemically investigated G6PD in lung cancer. G6PD expression was significantly associated with a higher pathological TNM stage (p = 0.0024), lymph node metastasis (p = 0.0187), poorer differentiation (p = 0.0046), pleural invasion (p = 0.0197), vascular invasion (p < 0.0001), lymphatic invasion (p = 0.0200) and poorer prognosis (p = 0.0005) in adenocarcinoma. Especially, G6PD-positive patients with overexpression at the invasive front had significantly poorer survival than those without overexpression (p = 0.0058). Moreover, multivariable analysis revealed that G6PD expression was an independent adverse-prognostic factor. These results suggest that G6PD may be a novel predictive prognostic marker for lung adenocarcinoma.