Abstract
BackgroundSchizophrenic patients show lower incidences of cancer, implicating schizophrenia may be a protective factor against cancer. To study the genetic correlation between the two diseases, a specific PPI network was constructed with candidate genes of both schizophrenia and hepatocellular carcinoma. The network, designated schizophrenia-hepatocellular carcinoma network (SHCN), was analysed and cliques were identified as potential functional modules or complexes. The findings were compared with information from pathway databases such as KEGG, Reactome, PID and ConsensusPathDB.ResultsThe functions of mediator genes from SHCN show immune system and cell cycle regulation have important roles in the eitology mechanism of schizophrenia. For example, the over-expressing schizophrenia candidate genes, SIRPB1, SYK and LCK, are responsible for signal transduction in cytokine production; immune responses involving IL-2 and TREM-1/DAP12 pathways are relevant for the etiology mechanism of schizophrenia. Novel treatments were proposed by searching the target genes of FDA approved drugs with genes in potential protein complexes and pathways. It was found that Vitamin A, retinoid acid and a few other immune response agents modulated by RARA and LCK genes may be potential treatments for both schizophrenia and hepatocellular carcinoma.ConclusionsThis is the first study showing specific mediator genes in the SHCN which may suppress tumors. We also show that the schizophrenic protein interactions and modulation with cancer implicates the importance of immune system for etiology of schizophrenia.
Highlights
Schizophrenic patients show lower incidences of cancer, implicating schizophrenia may be a protective factor against cancer
Schizophrenia candidate genes related to tumor suppression Despite the increased risk factors for the schizophrenic patients such as heavy smoking, poor diet habit and inadequate physical activities, the protective factor for cancer incidence in schizophrenic patients [16] such as TP53 and APC, which plays a key role in the susceptibility of schizophrenia and the reduced cancer risk by apoptosis [39,40,41,42], have implication of the explanation for less incidence of cancer for schizophrenic patients
To see the differential interaction between diseases in the protein-protein interactions (PPIs) network, schizophrenic candidate genes were examined from three different literature results and compared with the Brodman Area 22 (BA22) over- and underexpression genes with tumor suppression
Summary
Schizophrenic patients show lower incidences of cancer, implicating schizophrenia may be a protective factor against cancer. Sun J. et al (2008) surveyed the increased association studies from the SchizophreniaGene database in ethnic populations [5], in which candidate genes are selected and ranked by the combined odds ratio method as an important index of the candidate genes [6] It provides a basis for the investigation of molecular and cellular mechanisms of schizophrenia by the analysis of gene features for a genetic network. The identified pathway characteristics of schizophrenic candidate genes have important implications of molecular features for schizophrenia Another gene risk prediction study used the translational convergent functional genomics approach introduced by Ayalew M. et al (2012) to prioritize schizophrenia genes by genelevel integration of genome-wide association study data to identify top candidate genes [8]. The previous literatures provide different databases and integration of formulated reliability analysis, ranking and scoring for important candidate genes of schizophrenia
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