Abstract 1550: Limb-bud and heart inhibits the proliferation and metastasis of human lung adenocarcinoma cells and predicts survival outcome
Authors: Deng Mingming , Yu Ruoxi , Li Zhi , Che Xiaofang , Song Huicong , Wang Ximing , Zhang Zhe , Lv Qingjie , Wang Shuo , Qu Xiujuan , Liu Yunpeng , Zhang Ye , Hu Xuejun 
Published: August 2018

Background/Aims: Limb-bud and heart (LBH) is an important transcription cofactor involved in embryonic development. But, the role of LBH in human cancer remains less understood. The aim of this study was to explore the role of LBH in lung cancer, and its correlation with clinical characteristics and prognosis of lung cancer patients, especially those with lung adenocarcinoma (LUAD).

Methods: TCGA, GEO (GSE19188), Kaplan-Meier Plotter, and our own tissue microarray (TMA) containing 41 lung cancer tissues and paired normal tissues were used to compare the differences of LBH expression, and the relation with clinical characteristics. Another 70 LUAD tissues with patient follow-up records were used to explore the correlation of clinical characteristics and prognosis by Kaplan-Meier and Cox-regression analysis. Cell viability assay, wound healing assay, colony formation assay, transwell assay, and flow cytometry were used to explore the biological function of LBH on LUAD cells. In addition, bioinformatics analyses (GO pathway and Gene Set Enrichment Analysis) and Western blotting were carried out to determine the potential LBH pathways.

Results: LBH was significantly down-regulated in lung cancer tissues, and correlated with prognosis and clinical characteristics of lung cancer patients based on public database and TMA. Importantly, the expression level of LBH significantly correlated to depth of invasion (P=0.048), lymph node status (P=0.031), and TNM stage (P=0.007) of LUAD patients. Kaplan-Meier survival analysis revealed that LBH-negative was associated with the poor overall survival (OS) of LUAD patients (P=0.004). Cox univariate and multivariate regression analysis showed that LBH expression status was a favorable independent prognostic factor(hazard ratio [HR]=0.12, 95% confidence interval [CI]: 0.06-0.89, P=0.039).Knockdown of LBH accelerated LUAD cell proliferation, migration, and invasion. Furthermore, bioinformatics analyses indicated LBH was significantly related to the cell adhesion pathway. Western blotting confirmed that LBH could regulate several proteins of the integrin family (integrin-α1, integrin-α2, integrin-α4, integrin-αv and integrin-β4), but didn't influence EMT-related proteins.

Conclusion: Our data suggest that LBH plays an important role in lung cancer. Importantly, LBH is an independent prognostic factor in LUAD, and can inhibit the proliferation and metastasis of LUAD cells. LBH may be a potential prognostic biomarker in LUAD patients.

Citation Format: Mingming Deng, Ruoxi Yu, Zhi Li, Xiaofang Che, Huicong Song, Ximing Wang, Zhe Zhang, Qingjie Lv, Shuo Wang, Xiujuan Qu, Yunpeng Liu, Ye Zhang, Xuejun Hu. Limb-bud and heart inhibits the proliferation and metastasis of human lung adenocarcinoma cells and predicts survival outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1550.