Jing Ning1,2, Shenyi Jiang3, Xiaoxi Li4, Yang Wang1, Xuhong Deng1, Zhiqiang Zhang5, Lijie He5, Daqing Wang6, Youhong Jiang7. 1. Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Nanjingbei Street, Heping District, Shenyang, 110001, Liaoning Province, China. 2. 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, Shenyang, 110042, Liaoning Province, China. 3. Department of General Practice, The First Hospital of China Medical University, Nanjingbei Street, Heping District, Shenyang, 110001, Liaoning Province, China. 4. Central Laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China. 5. The People's Hospital of Liaoning Province, No.33 Wenyi Road, Shenhe District, Shenyang, 110016, Liaoning Province, China. 6. The People's Hospital of Liaoning Province, No.33 Wenyi Road, Shenhe District, Shenyang, 110016, Liaoning Province, China. 443058216@qq.com. 7. Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, Nanjingbei Street, Heping District, Shenyang, 110001, Liaoning Province, China. jiangyouhong2000@aliyun.com.
Abstract
BACKGROUND: Glypican 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: The 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.
BACKGROUND:Glypican 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: The 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.
Authors: William Lee; Zhaoshi Jiang; Jinfeng Liu; Peter M Haverty; Yinghui Guan; Jeremy Stinson; Peng Yue; Yan Zhang; Krishna P Pant; Deepali Bhatt; Connie Ha; Stephanie Johnson; Michael I Kennemer; Sankar Mohan; Igor Nazarenko; Colin Watanabe; Andrew B Sparks; David S Shames; Robert Gentleman; Frederic J de Sauvage; Howard Stern; Ajay Pandita; Dennis G Ballinger; Radoje Drmanac; Zora Modrusan; Somasekar Seshagiri; Zemin Zhang Journal: Nature Date: 2010-05-27 Impact factor: 49.962