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. The 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. 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 (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). Our analysis revealed a novel angiogenesis subtype classification in SCC and provides new insights into a hallmark of SCC progression.

中文翻译：

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鳞状细胞癌血管生成亚型综合分析

鳞状细胞癌 (SCC) 是一种具有独特管理复杂性的疾病，因为它显示出显着异质的分子亚型。然而，SCC 血管生成的情况尚未得到充分研究。基于血管生成相关基因和 TCGA 数据，使用 ConsensusClusterPlus 包建立 SCC 的血管生成相关亚型。我们分析了基因和 miRNA 的改变以及与血管生成亚型相关的通路。接下来，进一步研究了血管生成亚型的调控网络、与基因组特征、免疫微环境和临床特征的相关性。最后，还分析了血管生成相关亚型对 SCC 的预后影响。本研究共包括 1368 个 SCC 样本。然后基于163个血管生成相关基因，951名SCC患者的亚型1（血管生成亚型）和417名SCC的亚型2（非血管生成亚型）确定了两种血管生成亚型。GSEA 显示血管生成和上皮间质转化、炎症反应和缺氧在血管生成亚型中得到丰富。15 个免疫检查点中的 8 个（ADORA2A、BTLA、CD276、CYBB、HAVCR2、SIGLEC7、SIGLEC9 和 VTCN1）显着上调，而 C10orf54 在血管生成亚型中显着下调。生存分析显示，血管生成亚型患者的生存结果比非血管生成亚型患者差（无病间隔期 P = 0.017，总生存期 P = 0.00013）。