Fan Zhang1,2,3, Mengjuan Xue1,2,3, Xin Jiang1,2,3, Huiyuan Yu1,2,3, Yixuan Qiu1,2,3, Jiaming Yu1,2,3, Fan Yang4,5,6, Zhijun Bao7,8,9. 1. Department of Geriatric Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, No. 221 Yan'an West Road, Shanghai, 200040, People's Republic of China. 2. Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, No. 221 Yan'an West Road, Shanghai, 200040, People's Republic of China. 3. Research Center on Aging and Medicine, Fudan University, Shanghai, 200040, People's Republic of China. 4. Department of Geriatric Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, No. 221 Yan'an West Road, Shanghai, 200040, People's Republic of China. fdyangfan@fudan.edu.cn. 5. Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, No. 221 Yan'an West Road, Shanghai, 200040, People's Republic of China. fdyangfan@fudan.edu.cn. 6. Research Center on Aging and Medicine, Fudan University, Shanghai, 200040, People's Republic of China. fdyangfan@fudan.edu.cn. 7. Department of Geriatric Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, No. 221 Yan'an West Road, Shanghai, 200040, People's Republic of China. zhijunbao@fudan.edu.cn. 8. Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, No. 221 Yan'an West Road, Shanghai, 200040, People's Republic of China. zhijunbao@fudan.edu.cn. 9. Research Center on Aging and Medicine, Fudan University, Shanghai, 200040, People's Republic of China. zhijunbao@fudan.edu.cn.
Abstract
BACKGROUND: The incidence and mortality rates of hepatocellular carcinoma are among the highest of all cancers all over the world. However the survival rates are relatively low due to lack of effective treatments. Efforts to elucidate the mechanisms of HCC and to find novel prognostic markers and therapeutic targets are ongoing. Here we tried to identify prognostic genes of HCC through co-expression network analysis. METHODS: We conducted weighted gene co-expression network analysis with a microarray dataset GSE14520 of HCC from Gene Expression Omnibus database and identified a hub module associated with HCC prognosis. Function enrichment analysis of the hub module was performed. Clinical information was analyzed to select candidate hub genes. The expression profiles and survival analysis of the selected genes were performed using additional datasets (GSE45267 and TCGA-LIHC) and the hub gene was identified. GSEA and in vitro experiments were conducted to further verify the function of the hub gene. RESULTS: Genes in the hub module were mostly involved in the metabolism pathway. Four genes (SLC27A5, SLC10A1, PCK2 and FMO4) from the module were identified as candidate hub genes according to correlation analysis with prognostic indicators. All these genes were significantly down-regulated in tumor tissues compared with non-tumor tissues in additional datasets. After survival analysis and network construction, SLC27A5 was selected as a prognostic marker. GSEA analysis and in vitro assays suggested that SLC27A5 downregulation promoted tumor cell migration via enhancing epithelial-mesenchymal transition. CONCLUSION: SLC27A5 is a potential biomarker of HCC and SLC27A5 downregulation promoted HCC progression by enhancing EMT.
BACKGROUND: The incidence and mortality rates of hepatocellular carcinoma are among the highest of all cancers all over the world. However the survival rates are relatively low due to lack of effective treatments. Efforts to elucidate the mechanisms of HCC and to find novel prognostic markers and therapeutic targets are ongoing. Here we tried to identify prognostic genes of HCC through co-expression network analysis. METHODS: We conducted weighted gene co-expression network analysis with a microarray dataset GSE14520 of HCC from Gene Expression Omnibus database and identified a hub module associated with HCC prognosis. Function enrichment analysis of the hub module was performed. Clinical information was analyzed to select candidate hub genes. The expression profiles and survival analysis of the selected genes were performed using additional datasets (GSE45267 and TCGA-LIHC) and the hub gene was identified. GSEA and in vitro experiments were conducted to further verify the function of the hub gene. RESULTS: Genes in the hub module were mostly involved in the metabolism pathway. Four genes (SLC27A5, SLC10A1, PCK2 and FMO4) from the module were identified as candidate hub genes according to correlation analysis with prognostic indicators. All these genes were significantly down-regulated in tumor tissues compared with non-tumor tissues in additional datasets. After survival analysis and network construction, SLC27A5 was selected as a prognostic marker. GSEA analysis and in vitro assays suggested that SLC27A5 downregulation promoted tumor cell migration via enhancing epithelial-mesenchymal transition. CONCLUSION:SLC27A5 is a potential biomarker of HCC and SLC27A5 downregulation promoted HCC progression by enhancing EMT.
Authors: Ghassan K Abou-Alfa; Tim Meyer; Ann-Lii Cheng; Anthony B El-Khoueiry; Lorenza Rimassa; Baek-Yeol Ryoo; Irfan Cicin; Philippe Merle; YenHsun Chen; Joong-Won Park; Jean-Frederic Blanc; Luigi Bolondi; Heinz-Josef Klümpen; Stephen L Chan; Vittorina Zagonel; Tiziana Pressiani; Min-Hee Ryu; Alan P Venook; Colin Hessel; Anne E Borgman-Hagey; Gisela Schwab; Robin K Kelley Journal: N Engl J Med Date: 2018-07-05 Impact factor: 91.245
Authors: Josep M Llovet; Sergio Ricci; Vincenzo Mazzaferro; Philip Hilgard; Edward Gane; Jean-Frédéric Blanc; Andre Cosme de Oliveira; Armando Santoro; Jean-Luc Raoul; Alejandro Forner; Myron Schwartz; Camillo Porta; Stefan Zeuzem; Luigi Bolondi; Tim F Greten; Peter R Galle; Jean-François Seitz; Ivan Borbath; Dieter Häussinger; Tom Giannaris; Minghua Shan; Marius Moscovici; Dimitris Voliotis; Jordi Bruix Journal: N Engl J Med Date: 2008-07-24 Impact factor: 91.245
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702