Deng Mingming, Yu Ruoxi, Wang Shuo, Zhang Ye, Li Zhi, Song Huicong, Liu Bofang, Xu Ling, Wang Ximing, Zhang Zhe, Lv Qingjie, Wang Xiaonan, Che Xiaofang, Qu Xiujuan, Liu Yunpeng, Hu Xuejun
Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, China.
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
Cell Physiol Biochem. 2018;47(1):223-234. doi: 10.1159/000489801. Epub 2018 May 18.
BACKGROUND/AIMS: The transcription cofactor limb-bud and heart (LBH) is involved in embryonic development. However, its role in human lung cancer, especially lung adenocarcinoma (LUAD), remains unclear.
A public database and tissue microarray (TMA) were used to compare differences in LBH expression and its relationship with clinical characteristics. Tissue from an additional 70 LUAD patients with follow-up records was used to explore the correlation of LBH expression with prognosis. Cellular and molecular studies validated the role of LBH in LUAD growth and invasion.
LBH was significantly down-regulated in lung cancer tissue samples and was correlated with the prognosis and clinical characteristics of lung cancer patients based on a public database and TMA. Survival analysis revealed that LBH-negative expression was associated with poor overall survival of LUAD patients (P = 0.021). Cox regression analysis showed that LBH expression status was a favorable independent prognostic factor (hazard ratio = 0.120, 95% confidence interval = 0.016-0.894, P = 0.039). LBH knockdown accelerated LUAD cell proliferation, migration, and invasion. Furthermore, bioinformatics analysis indicated that LBH was significantly related to the cell adhesion pathway. Western blot analysis confirmed that LBH could regulate the expression of integrin family members (integrin-α1, integrin-α2, integrin-α4, integrin-αv, and integrin-β4).
Our data suggest that LBH plays an important role in lung cancer. Importantly, LBH is an independent prognostic factor in LUAD and can attenuate cell growth and invasion. LBH may be a potential prognostic biomarker in LUAD patients.
背景/目的：转录辅因子肢芽与心脏（LBH）参与胚胎发育。然而，其在人类肺癌，尤其是肺腺癌（LUAD）中的作用仍不清楚。
使用公共数据库和组织芯片（TMA）比较LBH表达差异及其与临床特征的关系。另外选取70例有随访记录的LUAD患者的组织，用于探究LBH表达与预后的相关性。细胞和分子研究验证了LBH在LUAD生长和侵袭中的作用。
基于公共数据库和TMA，LBH在肺癌组织样本中显著下调，且与肺癌患者的预后和临床特征相关。生存分析显示，LBH阴性表达与LUAD患者总体生存率低相关（P = 0.021）。Cox回归分析表明，LBH表达状态是一个良好的独立预后因素（风险比 = 0.120，95%置信区间 = 0.016 - 0.894，P = 0.039）。敲低LBH可加速LUAD细胞增殖、迁移和侵袭。此外，生物信息学分析表明，LBH与细胞黏附途径显著相关。蛋白质印迹分析证实，LBH可调节整合素家族成员（整合素-α1、整合素-α2、整合素-α4、整合素-αv和整合素-β4）的表达。
我们的数据表明，LBH在肺癌中起重要作用。重要的是，LBH是LUAD的独立预后因素，可减弱细胞生长和侵袭。LBH可能是LUAD患者潜在的预后生物标志物。
