Comprehensive Expression Profiles of Genes for Protein Tyrosine Phosphatases in Immune Cells
SCIENCE SIGNALING
Authors: Arimura, Yutaka; Yagi, Junji
Abstract
The phosphorylation and dephosphorylation of signaling molecules play a crucial role in various cellular processes, including immune responses. To date, the global expression profile of protein tyrosine phosphatases (PTPs) in various immune cells has not been described. With the RefDIC (Reference Genomics Database of Immune Cells) database compiled by RIKEN (Rikagaku Kenkyusho), we examined the expression patterns of PTP-encoding genes in mice and identified between 57 and 64 PTP-encoding genes (depending on cutoff values) that were commonly expressed in immune cells. Cells of different lineages contained additional, unique PTP-encoding genes, which resulted in a total of 58 to 76 genes. Compared with cells from nonimmune tissues, immune cells exhibited enhanced expression of the genes encoding 8 PTP-encoding genes, including Ptprc, Ptpn6, and Ptpn22, but had barely detectable expression of 11 PTP-encoding genes, including Ptprd and Tns1. Each immune cell lineage had between 2 and 18 PTP-encoding genes expressed at relatively high or low extents relative to the average expression among immune cells; for example, Ptprj in B cells, Dusp3 in macrophages, Ptpro in dendritic cells, and Ptprg in mast cells. These PTPs potentially play important roles in each cell lineage, and our analysis provides insight for future functional studies.
Systematic analysis of gene expression profiles reveals prognostic stratification and underlying mechanisms for muscle-invasive bladder cancer
CANCER CELL INTERNATIONAL
Authors: Zhang, Ping-Bao; Huang, Zi-Li; Xu, Yong-Hua; Huang, Jin; Huang, Xin-Yu; Huang, Xiu-Yan
Abstract
Background Muscle-invasive bladder cancer (MIBC) is originated in the muscle wall of the bladder, and is the ninth most common malignancy worldwide. However, there are no reliable, accurate and robust gene signatures for MIBC prognosis prediction, which is of the importance in assisting oncologists to make a more accurate evaluation in clinical practice. Methods This study used univariable and multivariable Cox regression models to select gene signatures and build risk prediction model, respectively. The t-test and fold change methods were used to perform the differential expression analysis. The hypergeometric test was used to test the enrichment of the differentially expressed genes in GO terms or KEGG pathways. Results In the present study, we identified three prognostic genes, KLK6, TNS1, and TRIM56, as the best subset of genes for muscle-invasive bladder cancer (MIBC) risk prediction. The validation of this stratification method on two datasets demonstrated that the stratified patients exhibited significant difference in overall survival, and our stratification was superior to three other stratifications. Consistently, the high-risk group exhibited worse prognosis than low-risk group in samples with and without lymph node metastasis, distant metastasis, and radiation treatment. Moreover, the upregulated genes in high-risk MIBC were significantly enriched in several cancer-related pathways. Notably, PDGFRB, a receptor for platelet-derived growth factor of PI3K-Akt signaling pathway, and TUBA1A were identified as two targets of multiple drugs. In addition, the angiogenesis-related genes, as well as two marker genes of M2 macrophage, CD163 and MRC1, were highly upregulated in high-risk MIBC. Conclusions In summary, this study investigated the underlying molecular mechanism and potential therapeutic targets associated with worse prognosis of high-risk MIBC, which could improve our understanding of progression of MIBC and provide new therapeutic strategies for the MIBC patients.