Comprehensive Analysis of Angiogenesis Subtype of Squamous Cell Carcinoma

Abstract Background: Squamous cell carcinoma (SCC) is a disease with distinct management complexities as it displays a remarkably heterogeneous molecular subtype. However, the landscape of angiogenesis for SCC is not fully investigated.Method and materials: The integrated analysis for the angiogenesis-related subtype for SCC and was performed using the ConsensusClusterPlus package based on angiogenesis-related genes and TCGA data respectively. We analyzed the alternation of the genes and miRNAs as well as pathways associated with angiogenesis. Next, we evaluated the prognostic value of the SCC subtype, the mode of regulation, the correlation with genomic characteristics, immune microenvironment, and clinical features of the angiogenesis subtypes.Results: Totally, a total of 1368 SCC samples were included in this study. Two angiogenesis subtypes were then identified based on the one hundred and sixty-three angiogenesis-related genes with subtype1 of 951 SCC patients and subtype2 of 417 SCC. GSEA revealed that angiogenesis and epithelial-mesenchymal transition, inflammatory response, hypoxia was enriched in the subtype1 and suggested that the subtype 1 were angiogenesis-subtype of SCC. Eight of the 15 immune checkpoints (ADORA2A, BTLA, CD276, CYBB, HAVCR2, SIGLEC7, SIGLEC9, and VTCN1) were significantly up-regulated while C10orf54 were significantly down-regulated in the angiogenesis subtype. The survival analysis revealed that the patients in the angiogenesis subtype have a poorer survival outcome than that in the non-angiogenesis subtype (P=0.017 for disease free interval and P=0.00013 for overall survival).Conclusion: Our analysis suggests that the importance of the angiogenesis pathway in SCC and may represent an underappreciated hallmark of SCC progression.