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Abstract：
Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant tumor of the skin. B7 homolog 4 (B7-H4) and B7-H5 (B7 homolog 5) are associated with a variety of tumors. Investigate the potential role of B7-H4 and B7-H5 in regulating the tumorigenesis and progression of CSCC. B7-H4 and B7-H5 transcriptome data were collected from GEO and TCGA databases and subjected to bioinformatical analysis by protein-protein interaction (PPI) network, functional enrichment analysis, immune analysis, and drug-gene interaction prediction analysis. We characterized the expression of B7-H4 and B7-H5 in carcinoma tissues of CSCC patients by immunohistochemistry. Meanwhile, the clinical correlation of B7-H4 and B7-H5 in CSCC was explored by statistical analysis. B7-H4 and B7-H5 genes were under-expressed in CSCC and correlated with tumor staging. According to GO and KEGG Pathway enrichment analysis, B7-H4, and B7-H5 can regulate the proliferation and activation of T cells, lymphocytes, and monocytes, and the expression of cytokines, such as IL-6 and IL-10, in CSCC. B7-H4 and B7-H5 are also jointly involved in the occurrence and development of CSCC via the JAK-STAT and Notch signaling pathways. We found that B7-H4 and B7-H5 proteins were abnormally highly expressed in CSCC tissue and correlated with tumor size and stage. Our findings offer new insights into the pathogenesis of CSCC and suggest that B7-H4 and B7-H5 are novel tissue biomarkers and promising therapeutic targets for CSCC.
摘要：
皮肤鳞状细胞癌(CSCC)是第二常见的皮肤恶性肿瘤。B7同源物4(B7-H4)和B7-H5(B7同源物5)与多种肿瘤相关。研究B7-H4和B7-H5在调节CSCC肿瘤发生和进展中的潜在作用。从GEO和TCGA数据库收集B7-H4和B7-H5转录组数据，并通过蛋白质-蛋白质相互作用（PPI）网络进行生物信息学分析，功能富集分析，免疫分析,和药物-基因相互作用预测分析。我们通过免疫组织化学表征了CSCC患者癌组织中B7-H4和B7-H5的表达。同时,通过统计学分析探讨B7-H4和B7-H5在CSCC中的临床相关性。B7-H4和B7-H5基因在CSCC中表达不足，并与肿瘤分期相关。根据GO和KEGG途径富集分析，B7-H4和B7-H5可以调节T细胞的增殖和活化，淋巴细胞，和单核细胞，和细胞因子的表达，如IL-6和IL-10，在CSCC。B7-H4和B7-H5还通过JAK-STAT和Notch信号通路共同参与CSCC的发生和发展。我们发现B7-H4和B7-H5蛋白在CSCC组织中异常高表达，并与肿瘤大小和分期相关。我们的发现为CSCC的发病机制提供了新的见解，并表明B7-H4和B7-H5是新型的组织生物标志物和有希望的CSCC治疗靶标。
