组织蛋白酶S(CTSS)基因编码赖氨酸半胱氨酸蛋白酶,在自身免疫性疾病的发展中起重要作用。炎症和神经系统疾病。此外,CTSS通过诱导肿瘤血管生成和肿瘤细胞外基质的降解参与肿瘤的侵袭和转移。然而,CTSS对预测泛癌症预后的确切影响及其对人类癌症中肿瘤微环境和免疫浸润的影响尚不清楚.本研究采用了一系列全面的生物信息学方法来评估CTSS的表达及其与预后的关系。临床病理特征,肿瘤微环境,肿瘤免疫浸润,许多癌症类型的肿瘤突变负担和微卫星不稳定性。当前的研究证明了CTSS在许多测试的癌症中的异常表达和不同的基因组改变谱。此外,CTSS表达与许多癌症的预后密切相关。在膀胱尿路上皮癌(BLCA)和皮肤皮肤黑色素瘤(SKCM)中,高CTSS表达与较好的总体生存率和疾病特异性生存率显着相关,但在脑低级胶质瘤(LGG)和葡萄膜黑色素瘤(UVM)中,结果较差。此外,CTSS分别在8种和12种癌症中与肿瘤突变负荷和微卫星不稳定性显著相关。以及免疫治疗子队列中的不同反应,尤其是黑色素瘤和膀胱癌。在上述四种癌症中,CTSS表达与基质和免疫细胞得分呈正相关。此外,CTSS表达与浸润CD8+T细胞数量相关,CD4+T细胞和巨噬细胞。相反,CTSS与静息肥大细胞呈负相关,BLCA中静息NK细胞和静息记忆CD4+T细胞浸润,SKCM与肾透明细胞癌(KIRC)。此外,CTSS表达与免疫相关基因表达相关,特别是BLCA中的PDCD1、LAG3、PDCD1和TIGIT,KIRC,SKCM,LGG和UVM。功能富集分析表明,CTSS可以驱动BLCA生物学功能和途径的动态调整,SKCM,LGG和UVM,包括免疫反应调节信号通路,淋巴细胞活化和T细胞受体单个通路的调节。目前的研究表明,CTSS可能是多种癌症预后和免疫浸润特征的重要生物标志物。
The cathepsin S (CTSS) gene encodes a lysine cysteine protease and serves an important role in the development of autoimmune diseases, inflammation and nervous system diseases. Furthermore, CTSS is implicated in tumor invasion and metastasis by the induction of tumor angiogenesis and the degradation of the tumor extracellular matrix. Nevertheless, the precise impact of CTSS on predicting pan-cancer prognosis and its influence on the tumor microenvironment and immune infiltration in human cancers remains unknown. This present study employed a comprehensive array of bioinformatic methods to evaluate the expression of CTSS and its associations with prognosis, clinicopathological characteristics, tumor microenvironment, tumor immune infiltration, tumor mutational burden and microsatellite instability across numerous cancer types. The current study demonstrated abnormal expression and distinct genomic alteration profiles of CTSS in many of the cancers tested. Furthermore, CTSS expression exhibited close associations with the prognosis of numerous cancers. High CTSS expression was significantly associated with better overall survival and disease-specific survival in bladder urothelial carcinoma (BLCA) and skin cutaneous melanoma (SKCM) but worse outcomes in brain lower grade glioma (LGG) and uveal melanoma (UVM). Moreover, CTSS demonstrated significant correlations with tumor mutational burden and microsatellite instability in 8 and 12 cancer types respectively, as well as different responses in immunotherapy sub-cohorts, especially in melanoma and bladder cancers. CTSS expression showed a positive correlation with stromal and immune cell scores in the four aforementioned cancers. Moreover, CTSS expression was correlated with the number of infiltrating CD8+ T cells, CD4+ T cells and macrophages. Conversely, CTSS was negatively associated with resting Mast cells, resting NK cells and resting memory CD4+ T cell infiltration in BLCA, SKCM and kidney renal clear cell carcinoma (KIRC). Furthermore, CTSS expression was correlated with immune-related gene expression, notably PDCD1, LAG3, PDCD1 and TIGIT in BLCA, KIRC, SKCM, LGG and UVM. Functional enrichment analysis suggested that CTSS could drive a dynamic adjustment of biological functions and pathways in BLCA, SKCM, LGG and UVM, including immune response regulating signaling pathways, regulation of lymphocyte activation and T cell receptor singling pathways. The current study suggested that CTSS could be an essential biomarker for prognosis and immune infiltration features in multiple cancers.