Heterotopic production of ceruloplasmin by lung adenocarcinoma is significantly correlated with prognosis
Heterotopic production of ceruloplasmin by lung adenocarcinoma is significantly correlated with prognosis
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DOI：
10.1016/j.lungcan.2018.01.012
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发表时间：
2018-04-01
期刊：
影响因子：
5.3
通讯作者：
Noguchi, Masayuki
中科院分区：
文献类型：
--
作者：
Matsuoka, Ryota;Shiba-Ishii, Aya;Noguchi, Masayuki
目的：铜蓝蛋白（CP）是一种众所周知的铜结合蛋白，主要在肝脏中合成，但已知其表达在癌症患者的血清和恶性肿瘤细胞中升高。肺癌是全世界癌症相关死亡的主要原因，而腺癌是肺癌的主要组织学类型。然而，CP在肺腺癌中的作用仍不清楚。在这里，我们检查并比较了肺腺癌各种组织学亚型中CP的表达及其与临床病理参数的相关性。材料和方法：我们使用定量实时RT-PCR和Western blot分析检查了肺腺癌样本和细胞系中的CP表达。对 196 例肺腺癌标本进行 CP 免疫组织化学检测。结果：CP 在侵袭性腺癌中的表达显着高于原位腺癌 (AIS)，并且与较差的预后、病理分期、pT 和 pN 显着相关。多变量分析显示CP表达是肺腺癌患者的独立预后因素。此外，使用从肺腺癌细胞系中提取的蛋白质进行蛋白质印迹分析揭示了CP的分泌形式。结论：CP在肺腺癌细胞中异位产生，其表达与肿瘤进展相关。鉴于肿瘤细胞中存在分泌形式的CP，CP可能是肺腺癌的有用生物标志物。
Objectives: Ceruloplasmin (CP) is a well-known copper binding protein synthesized mainly in the liver, but its expression is known to be elevated in the serum of cancer patients and in malignant tumor cells. Lung cancer is the leading cause of cancer-related death worldwide, and adenocarcinoma is the main histological type of lung cancer. However, the role of CP in lung adenocarcinoma is still unclear. Here we examined and compared the expression of CP in various histological subtypes of lung adenocarcinoma and its correlation with clinicopathological parameters.Materials and methods: We examined CP expression in lung adenocarcinoma samples and cell lines using quantitative real-time RT-PCR and Western blot analysis. Immunohistochemistry for CP was carried out using 196 specimens of lung adenocarcinoma.Results: CP expression was significantly higher in invasive adenocarcinoma than in adenocarcinoma in situ (AIS), and was significantly correlated with poorer outcome, pathological stage, pT, and pN. Multivariate analysis showed that CP expression was an independent prognostic factor for lung adenocarcinoma patients. Furthermore, Western blot analysis using protein extracted from lung adenocarcinoma cell lines revealed the secreted form of CP.Conclusion: CP is produced heterotopically in lung adenocarcinoma cells and its expression is associated with tumor progression. In view of the presence of the secreted form of CP in tumor cells, CP may be a useful biomarker for lung adenocarcinoma.