Abstract
Background: UBASH3B (STS1) is an important gene that negatively regulates T-cell receptor signaling in activated T-lymphocytes that involved in cancers. However, the function of UBASH3B in prostate cancer (PCa) and the correlation between UBASH3B and tumor-infiltrating immune cells still remain unclear.Methods: Real-time PCR and immunohistochemistry were applied to detect mRNA and protein expression of UBASH3B in PCa patients and benign prostate hyperplasia patients (BPH). Clinical features of patients with PCa were recorded and Kaplan Meier curve was subsequently plotted. Based on mRNA expression of UBASH3B, patients with PCa from TCGA database were divided into low-UBASH3B-expression group and high-UBASH3B-expression group for construct lncRNA-miRNA-mRNA network and analyzing GO and KEGG pathways. Single gene analysis method was performed by using GSEA to interpret gene expression data in PCa. The PPI network was constructed using STRING and the correlation between UBASH3B and tumor-infiltrating immune cells was analyzed by TIMER and CIBERSORT.Results: The mRNA and protein expression of UBASH3B were upregulated in PCa. The abundant expression of UBASH3B is associated with poor prognosis in PCa. The subnetwork of UBASH3B contains three lncRNAs (MIAT, LINC01297, MYLK-AS1) and four miRNAs (hsa-miR-200a-3p, hsa-miR-455-5p, hsa-miR-192-5p, hsamiR- 215-5P). The mRNA expression of UBASH3B was involved in 28 KEGG pathways. GSEA analysis showed that 18 hallmark gene sets were significantly enriched in high-UBASH3B-expression, whereas 1 gene set was enriched in low-UBASH3B-expression. PPI network revealed a tightly interaction between UBASH3B and LCP2 (an immune related gene). TIMER and CIBERSORT database indicated that UBASH3B was correlated with 11 types of tumor-infiltrating immune cells (naïve B cell, memory B cells, resting CD4+ memory T cell, activated CD4+ memory T cell, regulatory T cell, activated NK cell, M2 macrophages, resting dendritic cells, activated dendritic cells, resting mast cells, neutrophils).Conclusions: In conclusion, UBASH3B may be a novel potential prognostic biomarker and is associated with tumor-infiltrating immune cells in tumor microenvironment, suggesting UBASH3B as a potential target for future treatment of PCa.
Highlights
Prostate cancer (PCa) is the most common male malignant diseases in Western industrialized countries
Our results suggested that Ubiquitin-associated and SH3 domain-containing B (UBASH3B) may be a novel prognostic marker and was associated with tumor-infiltrating immune cells in prostate cancer
To investigate the mRNA expression level of UBASH3B in PCa and benign prostatic hyperplasia (BPH) tissues, real-time PCR was used and UBASH3B was found to be significantly upregulated in PCa tissues in comparison with BPH tissues (P = 0.0077) (Figure 1A)
Summary
Prostate cancer (PCa) is the most common male malignant diseases in Western industrialized countries. Despite the increasing numbers of PCa patients identified after prostatespecific antigen (PSA) screening, many cases have been initially diagnosed as metastatic cancer. Even if patient underwent surgical treatment, patients who did not find a micrometastatic mass before surgery would relapse. It seems that surgical treatment is difficult to achieve the effect of radical resection, patients have been suffering economic losses and pain all the time. It is important to identify potential micrometastases prior to surgery in order to be able to avoid surgery in PCa patients. The function of UBASH3B in prostate cancer (PCa) and the correlation between UBASH3B and tumor-infiltrating immune cells still remain unclear
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