UBASH3B Is a Novel Prognostic Biomarker and Correlated With Immune Infiltrates in Prostate Cancer

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.

[1]  Rebecca L. Siegel Mph,et al.  Cancer statistics, 2018 , 2018 .

[2]  Jun S. Liu,et al.  TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. , 2017, Cancer research.

[3]  Bo Hu,et al.  New insight into BIRC3: A novel prognostic indicator and a potential therapeutic target for liver cancer , 2018, Journal of cellular biochemistry.

[4]  Yingduan Cheng,et al.  Overexpression of a novel candidate oncogene KIF14 correlates with tumor progression and poor prognosis in prostate cancer , 2017, Oncotarget.

[5]  Salam A. Assi,et al.  UBASH3B/Sts-1-CBL axis regulates myeloid proliferation in human preleukemia induced by AML1-ETO , 2016, Leukemia.

[6]  C. Shaw,et al.  Anti-miR-148a regulates platelet FcγRIIA signaling and decreases thrombosis in vivo in mice. , 2015, Blood.

[7]  E. Klein,et al.  Low PCA3 expression is a marker of poor differentiation in localized prostate tumors: exploratory analysis from 12,076 patients , 2017, Oncotarget.

[8]  L. Zitvogel,et al.  TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer , 2017, Oncoimmunology.

[9]  Xinghuan Wang,et al.  Overexpression of short TRPM8 variant α promotes cell migration and invasion, and decreases starvation-induced apoptosis in prostate cancer LNCaP cells. , 2015, Oncology letters.

[10]  P. van der Geer,et al.  Identification of STS-1 as a novel ShcA-binding protein. , 2017, Biochemical and biophysical research communications.

[11]  UBASH3B promotes tamoxifen resistance and could be negatively regulated by ESR1 , 2017, Oncotarget.

[12]  E. Klein,et al.  Low PCA3 expression is a marker of poor differentiation in localized prostate tumors: Exploratory analysis from 12,076 patients. , 2017, Oncotarget.

[13]  John T. Wei,et al.  Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. , 2005, Cancer cell.

[14]  J. Kutok,et al.  Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells , 2016, Nature.

[15]  Philippe Foubert,et al.  PI3Kγ is a molecular switch that controls immune suppression , 2016, Nature.

[16]  Ash A. Alizadeh,et al.  Profiling Tumor Infiltrating Immune Cells with CIBERSORT. , 2018, Methods in molecular biology.

[17]  P. Doherty,et al.  Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2. , 2004, Immunity.

[18]  Qiang Yu,et al.  Protein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis , 2013, Proceedings of the National Academy of Sciences.