Abstract
BackgroundSquamous 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 materialsThe angiogenesis-related subtypes of SCC were established by using the ConsensusClusterPlus package based on angiogenesis-related genes and TCGA data. We analyzed the alteration of genes and miRNAs as well as pathways associated with angiogenesis subtypes. Next, the regulation network, the correlation with genomic characteristics, immune microenvironment, and clinical features of the angiogenesis subtypes were further investigated. Finally, the prognostic impact of the angiogenesis-related subtypes for SCC was also analyzed.ResultsA 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 (angiogenesis subtype) of 951 SCC patients and subtype2 (non-angiogenesis subtype) of 417 SCC. GSEA revealed that angiogenesis and epithelial-mesenchymal transition, inflammatory response, and hypoxia were enriched in the angiogenesis subtype. Eight of the 15 immune checkpoints (ADORA2A, BTLA, CD276, CYBB, HAVCR2, SIGLEC7, SIGLEC9, and VTCN1) were significantly upregulated while C10orf54 were significantly downregulated in the angiogenesis subtype. The survival analysis revealed that the patients in the angiogenesis subtype have poorer survival outcomes than those in the non-angiogenesis subtype (P = 0.017 for disease-free interval and P = 0.00013 for overall survival).ConclusionOur analysis revealed a novel angiogenesis subtype classification in SCC and provides new insights into a hallmark of SCC progression.
Highlights
Squamous cell carcinoma (SCC) represents the most common human solid tumor and is a major cause of cancer mortality [1]
Angiogenesis subtypes A total of 252 Cervical squamous cell carcinoma (CESC), 95 Esophageal squamous cell carcinomas (ESCA) 520 Head and neck squamous cell carcinoma (HNSC), and 501 Lung squamous cell carcinoma (LUSC) were included in this study
We divided the patients into subtype1 (951 SCC patients) and subtype2 (417 SCC patients) based on the one hundred and sixty-three genes of survival analysis (Fig. 1A)
Summary
Squamous cell carcinoma (SCC) represents the most common human solid tumor and is a major cause of cancer mortality [1]. Qin et al World Journal of Surgical Oncology (2021) 19:275 present in different SCC types [4, 5]. It is demonstrated that the smoking status is an important factor for the response of immune therapy for SCC like non-small cell lung cancer (NSCLC) [6]. The novel roles of the protein-coding genes were found in SCC regarding angiogenesis and aerobic glycolysis pathway [7,8,9,10]. SCCs share common histologic features and have similar molecular patterns, which are different from other cancer types [13]. Squamous cell carcinoma (SCC) is a disease with distinct management complexities as it displays a remarkably heterogeneous molecular subtype. The landscape of angiogenesis for SCC is not fully investigated
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