Bioinformatics Analysis and Validation Identify CDK1 and MAD2L1 as Prognostic Markers of Rhabdomyosarcoma

Abstract

Suying Lu,1,2,* Chengtao Sun,3,* Huimou Chen,1,2,* Chao Zhang,1,4,* Wei Li,5 Liuhong Wu,1,2 Jia Zhu,1,2 Feifei Sun,1,2 Junting Huang,1,2 Juan Wang,1,2 Zijun Zhen,1,2 Ruiqing Cai,1,2 Xiaofei Sun,1,2 Yizhuo Zhang,1,2 Xing Zhang1,6 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Pediatric Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 3Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of China; 4Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 5Department of Cardiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 6Department of Medical Melanoma and Sarcoma, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing ZhangDepartment of Medical Melanoma and Sarcoma, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, Guangdong 510060, People’s Republic of ChinaTel/Fax [phone]Email [email protected] Zhang Department of Pediatric OncologySun Yat-sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, Guangdong 510060, People’s Republic of ChinaTel/Fax [phone]Email [email protected]: The goal of the current study was to identify potential prognostic biomarkers of rhabdomyosarcoma (RMS).Materials and Methods: We screened chip sequencing datasets of RMS through the gene expression omnibus (GEO) database. A total of 74 RMS patient tissues and 39 normal muscle cell tissues were analyzed. Limma R software was used to identify the differentially expressed genes (DEGs) between RMS tissues and normal controls. The GO plot R package was used to visualize the results of the GO analysis. We screened for pathaffy package enrichment of DEGs by the Kyoto Encyclopedia of Genes and Genomes (KEGG). The cutoff criterion was a P-value < 0.05. Immunohistochemistry (IHC) was applied to validate the expression of CDK1 (cyclin-dependent kinases 1) and MAD2L1 (Mitotic Arrest Deficient 2 Like 1) in RMS.Results: We obtained a total of 498 up- and 480 down-regulated DEGs. The hub genes are mainly involved in the cell cycle and P53 singling pathway. CDK1 expression was associated with tumor size and COG-STS (Children’s Oncology Group-soft tissue sarcoma) staging of RMS. For the low CDK1 expression group and high CDK1 expression group, the 5-year overall survival (OS) rate was 83.0% vs 63.5% (P = 0.004), and the 5-year event-free survival (EFS) rate was 47.5% vs 27.5% (P = 0.049) respectively. When compared low MAD2L1 expression group with high MAD2L1 expression group, the 5-year OS rate was 80.0% vs 43.2% (P = 0.001), and the 5-year EFS rate was 45.1% vs 21.8% (P = 0.038), respectively. If patients were divided into three groups: low CDK1 and low MAD2L1 expression group, high CDK1 or high MAD2L1 expression group, and high CDK1 and high MAD2L1 expression group, the 5-year OS rate was 87.1%, 58.6%, 39.6% (P = 0.001), while the 5-year EFS rate of RMS patients was 54.2%, 23.2%, 21.7% (P = 0.028), respectively.Conclusion: This study has identified that CDK1 and MAD2L1 were adverse prognostic factors of RMS.Keywords: rhabdomyosarcoma, GEO, TCGA, CDK1, MAD2L1, prognosis

Keywords

• rhabdomyosarcoma
• geo
• tcga
• cdk1
• mad2l1
• prognosis.