Bioinformatic analysis identifying Arylsulfatase B as a novel biomarker for cancer prognosis with a highlight on stomach adenocarcinoma

Abstract Arylsulfatases are lysosomal enzymes with important function in the cell metabolism. Studies have demonstrated that the lysosomal protein arylsulfatase B (ARSB) may play roles in tumorigenesis and metastatic potential of tumor cells. However, the relationship between ARSB and stomach adenocarcinoma (STAD) has not yet been established. The aim of this study was to investigate the prognostic value of ARSB in cancers, particularly STAD and explore the potential underlying mechanisms. Gene expression data and detailed clinical information of cancer cases were obtained from multiple public databases. Subsequently, a series of bioinformatics analyses were used to elucidate the effects of ARSB on malignant tumors including STAD. The results demonstrated that ARSB was up-regulated in 15 cancers including STAD, and down-regulated in 10 cancers. In most cancers, ARSB expression was significantly related with CNA, methylation levels, and overall survival time. In STAD, ARSB was positively related with ESTIMATE Score (r = 0.54, p < 0.001), Immune Score (r = 0.35, p < 0.001), Stromal Score (r = 0.65, p < 0.001), and negatively related with Tumor Purity (r = -0.54, p < 0.001), TMB value (r = -0.13, p = 0.0092) and MSI value (r = -0.16, p = 0.0015). Meanwhile, ARSB are related with 11 tumor-infiltrating immune cells and immune checkpoint genes including LAG3, TIGIT and PDCD1. TNN mutation widely occurred in both high- and low-ARSB expression group. ARSB was found to be related to a variety of drug sensitivities, including lapatinib (r = 0.19, P < 0.001), acetalax (r = 0.18, P < 0.001), osimertinib (r = 0.17, P < 0.001), ABT737 (r = 0.14, P < 0.001), afatinib (r = 0.14, P < 0.001), spitinib (r = 0.13, P < 0.001). Thus, ARSB might be a potential therapeutic target and prognostic biomarker for cancers, especially STAD.