GPC3 affects the prognosis of lung adenocarcinoma and lung squamous cell carcinoma

BMC Pulmonary Medicine

Xiaoxi Li¹  Shenyi Jiang²  Youhong Jiang³  Yang Wang³  Xuhong Deng³  Jing Ning⁴  Zhiqiang Zhang⁵  Lijie He⁵  Daqing Wang⁵ 

[1] Central Laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, No. 44 Xiaoheyan Road, Dadong District, 110042, Shenyang, Liaoning Province, China;Department of General Practice, The First Hospital of China Medical University, Nanjingbei Street, Heping District, 110001, Shenyang, Liaoning Province, China;Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Nanjingbei Street, Heping District, 110001, Shenyang, Liaoning Province, China;Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Nanjingbei Street, Heping District, 110001, Shenyang, Liaoning Province, China;Department of General Medicine (VIP Ward) and Department of Tumor Supportive and Palliative Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, No.44 Xiaoheyan Road, Dadong District, 110042, Shenyang, Liaoning Province, China;The People’s Hospital of Liaoning Province, No.33 Wenyi Road, Shenhe District, 110016, Shenyang, Liaoning Province, China;

关键词: Lung adenocarcinoma;    Lung squamous cell carcinoma;    Glypican 3;    Differential expression analysis;    Protein–protein interaction network;    Risk-score model;   

DOI  :  10.1186/s12890-021-01549-9

来源: Springer

【 摘 要 】

BackgroundGlypican 3 (GPC3) is a heparin sulphate proteoglycan whose expression is associated with several malignancies. However, its expression in non-small-cell lung carcinoma (NSCLC) is limited and ambiguous. This study aimed to comprehensively evaluate the expression of GPC3 in NSCLC and develop a risk-score model for predicting the prognosis of NSCLC.MethodsThe gene expression profiles of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were downloaded from the UCSC Xena database. Using the limma package, the differentially expressed genes (DEGs) between different comparison groups were analysed and the differential expression of GPC3 was calculated. A functional enrichment analysis was conducted for GPC3-associated genes using the DAVID tool. For the GPC3-associated genes shared by the four comparison groups, a protein–protein interaction network was built using the Cytoscape software. After conducting a survival analysis and a Cox regression analysis, the genes found to be significantly correlated with prognosis were selected to construct a risk-score model. Besides, the gene and protein levels of GPC3 were examined by quantitative reverse transcriptase-PCR (qRT-PCR) and immunohistochemistry (IHC) in LUSC tissues and paracancer tissues.ResultsThe differential expression of GPC3 was significant (adjusted P < 0.05) in the NSCLC vs. normal, LUAD vs. normal, LUSC versus normal, and LUAD versus. LUSC comparison groups. GPC3 directly interacted with SERPINA1, MFI2, and FOXM1. Moreover, GPC3 expression was significantly correlated with pathologic N, pathologic T, gender, and tumour stage in LUAD samples. Finally, the risk-score model (involving MFI2, FOXM1, and GPC3) for LUAD and that (involving SERPINA1 and FOXM1) for LUSC were established separately. The qRT-PCR result showed that GPC3 expression was much higher in the LUSC tissues than that in the normal group. The IHC results further showed that GPC3 is highly expressed in LUSC tissues, but low in paracancer tissues.ConclusionThe three-gene risk-score model for LUAD and the two-gene risk-score model for LUSC might be valuable in improving the prognosis of these carcinomas.

【 授权许可】

CC BY