Lang Chen1,2,3, Xuan Liao1,3, Xiao Jiang1,3, Jianxin Yan1,3, Jiaji Liang1,3, Liu Hongwei4,5. 1. Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People's Republic of China. 2. Department of Burns and Plastic, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China. 3. Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, 510630, People's Republic of China. 4. Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People's Republic of China. liuhongwei05211@163.com. 5. Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, 510630, People's Republic of China. liuhongwei05211@163.com.
Abstract
INTRODUCTION: Cutaneous squamous cell carcinoma (cSCC) is a global malignant tumor with a high degree of malignancy. Once metastasis occurs, it will lead to poor prognosis and even death. This study attempts to find out the central genes closely related to cSCC metastasis, so as to clarify the molecular regulatory mechanism of cSCC metastasis and open up new ideas for clinical treatment. METHODS: Firstly, cSCC data set GSE98767 was used to establish a tumor metastasis model via clustering analysis. The key module and hub genes associated with cSCC metastasis were analyzed by weighted gene co-expression analysis (WGCNA). Next, the prognostic functions of hub genes were identified by functional and pathway enrichment analysis, pan-cancer analysis, and receiver operating characteristic-area under the curve (ROC-AUC) validation. Finally, the key genes were verified by clinical sample detection and biological in vitro test. RESULTS: A total of 19 hub genes related to cSCC metastasis were identified. They were highly expressed in cSCC metastatic tissues and were mainly enriched in cellular material and energy metabolism pathways. Overall survival (OS) and disease-free survival (DFS) results from pan-cancer analysis showed that eight and six highly expressed genes, respectively, with PAPSS2 and SCG5 had highly reliable ROC-AUC validation values and were poor prognostic factors. Clinical and biological tests also confirmed the upregulation of PAPSS2 and SCG5 in cSCC. Deletion of PAPSS2 and SCG5 resulted in decreased viability, migration, and invasion of A-431 cells. CONCLUSION: PAPSS2 and SCG5 may be important factors for cSCC metastasis, and they are involved in the regulation of cSCC cell viability, migration, and invasion.
INTRODUCTION: Cutaneous squamous cell carcinoma (cSCC) is a global malignant tumor with a high degree of malignancy. Once metastasis occurs, it will lead to poor prognosis and even death. This study attempts to find out the central genes closely related to cSCC metastasis, so as to clarify the molecular regulatory mechanism of cSCC metastasis and open up new ideas for clinical treatment. METHODS: Firstly, cSCC data set GSE98767 was used to establish a tumor metastasis model via clustering analysis. The key module and hub genes associated with cSCC metastasis were analyzed by weighted gene co-expression analysis (WGCNA). Next, the prognostic functions of hub genes were identified by functional and pathway enrichment analysis, pan-cancer analysis, and receiver operating characteristic-area under the curve (ROC-AUC) validation. Finally, the key genes were verified by clinical sample detection and biological in vitro test. RESULTS: A total of 19 hub genes related to cSCC metastasis were identified. They were highly expressed in cSCC metastatic tissues and were mainly enriched in cellular material and energy metabolism pathways. Overall survival (OS) and disease-free survival (DFS) results from pan-cancer analysis showed that eight and six highly expressed genes, respectively, with PAPSS2 and SCG5 had highly reliable ROC-AUC validation values and were poor prognostic factors. Clinical and biological tests also confirmed the upregulation of PAPSS2 and SCG5 in cSCC. Deletion of PAPSS2 and SCG5 resulted in decreased viability, migration, and invasion of A-431 cells. CONCLUSION: PAPSS2 and SCG5 may be important factors for cSCC metastasis, and they are involved in the regulation of cSCC cell viability, migration, and invasion.
Authors: Maxim V Kuleshov; Matthew R Jones; Andrew D Rouillard; Nicolas F Fernandez; Qiaonan Duan; Zichen Wang; Simon Koplev; Sherry L Jenkins; Kathleen M Jagodnik; Alexander Lachmann; Michael G McDermott; Caroline D Monteiro; Gregory W Gundersen; Avi Ma'ayan Journal: Nucleic Acids Res Date: 2016-05-03 Impact factor: 16.971
Authors: Tanya Barrett; Stephen E Wilhite; Pierre Ledoux; Carlos Evangelista; Irene F Kim; Maxim Tomashevsky; Kimberly A Marshall; Katherine H Phillippy; Patti M Sherman; Michelle Holko; Andrey Yefanov; Hyeseung Lee; Naigong Zhang; Cynthia L Robertson; Nadezhda Serova; Sean Davis; Alexandra Soboleva Journal: Nucleic Acids Res Date: 2012-11-27 Impact factor: 16.971