To identify novel genes in castration-resistant prostate cancer (CRPC), we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus (GEO). R packages affy and limma were performed to identify differentially expressed genes (DEGs) between primary prostate cancer and CRPC. After that, we performed functional enrichment analysis including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway. In addition, protein-protein interaction (PPI) analysis was used to search for hub genes. Finally, to validate the significance of these genes, we performed survival analysis. As a result, we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets. Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosterone-regulated sodium reabsorption pathway. PPI network identified hub genes like cortactin-binding protein 2 (CTTNBP2), Rho family guanosine triphosphatase (GTPase) 3 (RND3), protein tyrosine phosphatase receptor-type R (PTPRR), Jagged1 (JAG1), and lumican (LUM). Based on PPI network analysis and functional enrichment analysis, we identified two genes (PTPRR and JAG1) as key genes. Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer. In conclusion, PTPRR and JAG1 are key genes in the CRPC, which may serve as promising biomarkers of diagnosis and prognosis of CRPC.
Computational Biology/methods* ; Gene Ontology ; Humans ; Jagged-1 Protein/genetics* ; Male ; Prognosis ; Prostatic Neoplasms, Castration-Resistant/mortality* ; Protein Interaction Maps ; Receptor-Like Protein Tyrosine Phosphatases, Class 7/genetics*

OBJECTIVETo explore the genetic association between protein tyrosine phosphatase receptor type R (PTPRR) gene polymorphism and major depressive disorder (MDD) and its endophenotype.

METHODSA total of 517 unrelated MDD patients and 455 unrelated healthy subjects were recruited in this study to detect 11 single nucleotide polymorphisms (SNPs) in the PTPRR locus. They all were of the Chinese Han origin. Genotyping of SNPs was performed by matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) -based genotyping approach. The UNPHASED program was applied to analyze the genotyping data.

RESULTSOf the 11 selected SNPs, no significant allelic and genotypic association was found between MDD patients and the normal controls (corrected P > 0.05). However, analysis of haplotypes showed that the three SNPs haplotype rs1398599 (C) -rs2175711 (A) - rs4489789 (T) (P = 0.0023, OR = 1.334, 95% CI = 1.104-1.612) and four SNPs haplotype rs11178391 (C) -rs1398599 (C) -rs2175711 (A)-rs4489789(T) (P = 0.0063, OR = 1.281, 95% CI = 1.059-1.549) were associated with increased risk of MDD. Quantitative trait analysis revealed that rs2203231 in the PTPRR locus had strong allelic and genotypic association with the raw score of long-term memory (P = 0.0038 for allelic association, P = 0.0024 for genotypic association), the scaled score of long-term memory (P = 0.0057 for allelic association, P = 0.0038 for genotypic association), the raw score of short-term memory (P = 0.0027 for allelic association, P = 0.0015 for genotypic association), and the scaled score of short-term memory (P = 0.0035 for allelic association, P = 0.002 for genotypic association) in MDD patients.

CONCLUSIONThe polymorphism of PTPRR gene rs2203231 may be associated with the impairment of long-term and short-term memories in MDD patients.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Depressive Disorder, Major ; genetics ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptor-Like Protein Tyrosine Phosphatases, Class 7 ; genetics ; Young Adult