CTSV是一种可能的肿瘤标志物并与肾上腺皮质癌的免疫浸润密切相关

CTSV Is a Possible Tumor Marker and Is Closely Related to Immune Invasion of Ad-renal Cortical Carcinoma

摘要: 目的：组织蛋白酶V (cathepsin V, CTSV)最近被认为是一种致癌调节剂，在肿瘤细胞的生长增殖中发挥关键作用。然而，CTSV和肾上腺皮质癌之间的关联仍然未知。本研究通过生物信息学的方法探究其在肾上腺皮质癌中的表达情况及与预后间的关系，并通过功能分析和免疫浸润分析解释其关联。方法：运用R语言提取TCGA、GTEx和GEO数据库中肾上腺皮质癌与正常肾上腺皮质相关信息，分析CTSV在其中的表达差异，采用单/多因素Cox分析其与预后间的关系；通过GO、KEGG和GSEA富集分析研究其可能的机制；最后运用ssGSEA富集分析与TIMER2.0数据库研究CTSV在肾上腺皮质癌中与免疫浸润之间的联系。结果：CTSV在肾上腺皮质癌中表达水平显著升高(P < 0.001)。CTSV表达水平与N分期、M分期、预后分期和切缘肿瘤阳性显著正相关，CTSV高表达是肾上腺皮质癌预后的独立危险因素。此外，CTSV可能通过免疫反应调节、免疫反应激活、靶向E2F和细胞有丝分裂等多个信号通路参与肾上腺皮质癌的发生发展过程，与肾上腺皮质癌中的免疫浸润细胞均存在显著相关性。结论：CTSV在肾上腺皮质癌中显著高表达与预后不良密切相关，是肾上腺皮质癌患者的重要生物标志物，并参与肿瘤局部免疫反应的调节影响免疫细胞浸润水平，具有肾上腺皮质癌药物靶点的潜能。

Abstract: Objective: Cathepsin V (CTSV) has recently been recognized as an oncogenic modulator and plays a key role in the growth and proliferation of tumor cells. However, the association between CTSV and adrenal cortical carcinoma remains unknown. In this study, the expression and relationship between adrenal cortical carcinoma and prognosis were explored by bioinformatics, and the asso-ciation was explained by functional analysis and immune invasion analysis. Methods: The R lan-guage was used to extract the relevant information of adrenal cortex carcinoma and normal adrenal cortex in TCGA, GTEx and GEO databases, analyze the expression difference of CTSV therein, and analyze the relationship between it and prognosis by single/multivariate Cox. The possible mech-anisms of GO, KEGG, and GSEA enrichment analysis were investigated. Finally, ssGSEA enrichment analysis and TIMER2.0 database were used to study the relationship between CTSV and immune invasion in adrenal cortical carcinoma. Results: The expression level of CTSV in adrenal cortical car-cinoma was significantly increased (P < 0.001). CTSV expression levels were positively correlated with N stage, M stage, prognostic stage and positive resection margin tumor, and high CTSV expres-sion was an independent risk factor for the prognosis of adrenal cortex carcinoma. In addition, CTSV may be involved in the development and development of adrenal cortical carcinoma through multiple signaling pathways such as immune response regulation, immune response activation, targeting of E2F and cell mitosis, which is significantly correlated with immune-infiltrating cell cleavage in adrenal cortical carcinoma. Conclusion: The significantly high expression of CTSV in adrenal cortex carcinoma is closely related to poor prognosis, and is an important biomarker for patients with adrenocortical carcinoma, and participates in the regulation of local immune response of tumors and affects the level of immune cell infiltration, which has the potential of drug targets for adrenocortical carcinoma.