Alteration And Expression Study Of DOCK Family Genes In Liver Cancer By Bioinformatics Method

Objectives:Cancer genomics study has revealed alterations and abnormal expression of DOCK(Dedicator of Cytokinesis)family genes in cancer,though the underlying mechanisms are still unknown.In this research,we analyzed cancer genomics transcriptome data by using bioinformatics method,aiming at revealing mutation and expression profiles of DOCK family genes in liver cancer and predicting their function in the development of liver cancer.Methods:Firstly,we analyzed the molecular evolution of DOCK family genes from 7 species and the conserve domains of the homologues by comparing the sequences using software like Mega and Clustal;Secondly,we screened out recurrent mutational genes in human DOCK genes and predict their impact on the development of liver cancer by analyzing mutation data in different cancers from cancer genomics database TCGA;Then we dig out the expression differences of DOCK proteins between cancer samples(especially liver cancer)and normal samples by analyzing public database(GEO,TCGA).Results:Forty-five members of DOCK gene family were found in seven species and they are evolutionarily conserved.Certain gene locus of the 11 family members in human DOCK genes shows conservative trait;The mutation frequency of DOCK2 and DOCKIO is relatively higher among various cancers;In liver cancer,the mutation frequency of DOCK2(6%)and DOCKIO(9%)is the highest respectively in HCC and ICC;Point mutation of SH3,DHR-1 and DHR-2 domain in some of the DOCK genes can lead to protein secondary structural transformation.Also,the Kaplan-Meier survival rate of patients with DOCK2 mutational liver cancer is decreased;The expression volume of DOCK2 and DOCK10 protein in liver cancer is lower than that in normal ones,while the expression of downstream pathway genes(CDC42?RAC3?PAK2?RAC1)of DOCK2 and DOCKIO are up-regulated in liver cancer.Conclusions:It is universally observed in cancers that DOCK family genes are mutated and abnormally expressed,especially in liver cancer.Bioinformatics study reveals DOCK2 and DOCK10 are recurrently mutated and less expressed and may be tumor-suppressed genes in liver cancer.