Bioinfomatics Analysis Of Imatinib-resistant Genes And Expression Of CCNA2 In Gastrointestinal Stromal Tumor

ObjectiveScreen hub genes related to the occurrence and development of imatinib-resistant gastrointestinal stromal tumors(GIST)by bioinformatics analysis tools.The biological functions of their key genes,the signal pathways involved and the specific molecular mechanisms were analyzed to provide a theoretical basis for further development of GIST treatment strategies.Methods1 Bioinformatics analysis of genes related to imatinib resistant gastrointestinal stromal tumors(1)Download the chip data and platform files numbered GSE132542 from the common database GEO of gene chip expression;(2)Quality control and background correction for the downloaded raw data;(3)Thermal and volcanic maps were drawn based on the differentially expressed genes obtained;(4)The DAVID software was used to carry out GO functional annotation and KEGG pathway enrichment analysis on the differentially expressed genes;(5)The protein-protein interaction network analysis was constructed by using STRING database and Cytoscape software,and then the key node genes and hub modules were screened out;(6)Analysis of cellular localization,biological function and related signaling pathways for key node genes and hub modules excavated.2 Expression of 2CCNA2 in gastrointestinal stromal tumors(1)Screening and collecting clinical data of 62 newly diagnosed GIST patients confirmed by postoperative histopathology;(2)The CCNA2 expression of paraffin-embedded specimens after GIST was detected by immunohistochemical staining;(3)Data collation,screening and statistical analysis by SPSS25.0 software.Result1 Bioinformatics analysis of genes related to imatinib resistant gastrointestinal stromal tumors(1)A total of 333 differentially expressed genes were screened from the downloaded gene chip data,among which 204 were up-regulated and 129 were down-regulated.(2)In the analysis of signaling pathways,up-regulated genes are associated with cell cycle,oocyte meiosis,progesterone-mediated oocyte maturation,ubiquitin-mediated proteolysis,and amino acid biosynthesis.Down-regulated genes mainly involve the neuroactive ligand-receptor interaction,Hippo signaling pathway,cGMP-PKG signaling pathway and other related pathways.(3)Through the analysis of the protein interaction network of differentially expressed genes,10 key node genes and 2 important hub modules were selected and analyzed.2 Expression of 2CCNA2 in gastrointestinal stromal tumors(1)CCNA2 positive expression rate have no correlation with sex,age,location,tumor size,stage,distant metastasis,mitotic count,and risk grade.(2)The disease-free survival of GIST patients with CCNA2 positive expression was significantly lower than that of those with CCNA2 negative expression and it was an independent factor affecting the prognosis of patients.(3)In the GIST subgroup,CCNA2 positive expression rate of imatinib resistance group was significantly higher than that in the primary group,and the positive expression rate of CCNA2 might be associated with GIST imatinib resistance and poor prognosis.ConclusionThe overexpression of CCNA2,PLKl and AURKA was associated with imatinib-resistant gastrointestinal stromal tumors.Its biological functions and co-involved signaling pathways may play an important role in the pathogenesis of imatinib-resistant gastrointestinal stromal tumors.Overexpression of CCNA2 is an independent risk factor affecting the prognosis of GIST patients and may be associated with GIST imatinib resistance and poor prognosis.