The Investigation Of Mechanism Of Modular Network And CeRNA Regulatory Network Based On Bioinformatics In Gastric Cancer

1Background and purposeGastric cancer is one of the most common malignant tumors in the world.According to WHO statistics in 2012,there are more than 950,000 new cases of gastric cancer in the world every year.The number of deaths due to gastric cancer exceeds 720,000 each year,and the mortality rate accounts for the third place in malignant tumors.According to the data of China Cancer Registry in 2015,the incidence and mortality of gastric cancer are increasing year by year,second only to lung cancer,which is a serious threat to human health and life.In recent years,with the rapid development of gastric cancer treatment,the program has gradually improved,the 5-year mortality rate of early gastric cancer has decreased significantly,and the 5-year mortality rate of advanced gastric cancer is still as high as 30%-50%.In addition,the early diagnosis of gastric cancer is still at a low level.At present,with the deep research on the molecular level of gastric cancer,it is believed that the occurrence of gastric cancer is the result of the combination of genetic and environmental factors,and it is a process involving multiple pathways,multiple stages,and multiple genes.It has been found that there is a significant correlation between the polymorphism of susceptibility genes and the susceptibility to gastric cancer.It is believed that the variation of susceptibility genes can lead to gastric cancer thorough some functions or pathways in this population than other people.Such as oxidative damage,inflammatory response,DNA damage repair,mucosal protection and cell proliferation ability and so on.Due to the lack of convenient and sensitive early detection of biomarkers and effective treatment,gastric cancer is more likely to progress,metastasis,and ultimately death.Therefore,the search for new potential biomarkers related to the early diagnosis,treatment and prognosis of gastric cancer has become a research hotspot.In the past few years,precision medicine has profoundly changed the therapeutic prospects of some malignant tumors.Medical precision has led to significant improvements in global cancer treatment and has made the "one size fits all" era a thing of the past.However,the progression of gastric cancer is slow and difficult compared to the steady increase in survival rates for most types of cancer.In fact,despite some notable innovations,there is an urgent need to gain a deeper understanding of the genetic and molecular context of this cancer and to seek new treatments.Bioinformatics is an interdisciplinary subject,involving many fields.High-throughput technology is one of its core contents.By using its rigorous and complex algorithms,it studies the intrinsic mechanism of expression and regulation,and reveals the essential laws of human diseases.Especially in the role of tumor is particularly important,for more accurate,comprehensive,rapid diagnosis and effective treatment of disease conditions.The Cancer Genome Atlas(TCGA)is a project launched in 2005 that uses genome sequencing and bioinformatics to build a genome atlas of a wide range of cancers.The TCGA database contains 33 cancer types and more than 10,000 patient samples.It contains a large amount of tumor gene information and corresponding clinical data,which is a rich resource for further analysis and exploration of tumor development mechanisms at the molecular level.This study consists of the following two parts:The first part of this study uses WGCNA(Weighted correlation network analysis)method to analyze and construct a module for the significant expression of gastric cancer,and combines the clinical characteristics of the disease to explore the module gene network and attention.Correlation between phenotypes and further analysis of the most critical pivot genes in the recognition module network.The second part is based on the results of WGCNA analysis and RNA difference analysis,and based on bioinformatics methods,constructs ceRNA regulatory network,further analyzes the potential biological functions of ceRNA,and explores possible mechanisms in gastric cancer-specific ceRNA networks in gastric cancer.2Methods and results2.1 WGCNA analysis explores module networkThe WGCNA method was used to analyze the clinical characteristics of gastric cancer and to construct a gene expression module of gastric cancer.The correlation between the module gene network and the phenotype of interest was explored,and the hub gene in the module network was identified.The WGCNA analysis results in 14 modules.The module-feature correlation results show that 8 modules red,megenta,yellow,brown,cyan,pink,salmon,blue and pathologic_T(tumor T stage)are correlated,and the red module(cor=0.31,p=6e-09)is the most relevant.The results of gene function analysis in the red module indicate that the pathways and functions of the module genes are mainly related to tumors and immunity.By setting the GS(gene significance)>0.2 and MM(module identity)>0.85 threshold,the pivot gene in the red module was selected,and 22 hub genes were screened out,among which HAVCR2,CYBB,LAIR1,SLAMF8 and CD86 were The five highest MM genes.These five genes are mainly related to tumor immune activity,may participate in the development of gastric cancer by mediating the immune response of gastric cancer,and provide potential molecular targets for the treatment of gastric cancer.2.2 ceRNA regulatory networkBased on the results of differential gene and WGCNA analysis,bioinformatics methods were used to predict the database miRDB through the miRcode database and the miRNA target gene.TargetScan and miRTarBase successfully constructed a ceRNA regulatory network associated with gastric cancer-specific lncRNA,including 6 lncRNAs,10 miRNAs,and 44 target mRNAs.The potential biological functions of ceRNA were analyzed.The results showed that ceRNA mainly participates in tumor-related pathways and mediates the development of gastric cancer.In addition,the survival analysis of RNAs in ceRNA showed that lncRNAs PVT1:miRNA mir-137,mir-145,mir-96 and target mRNA ANGPT2 are closely related to the prognosis of gastric cancer patients,providing new potential for the treatment and prognosis of gastric cancer.Molecular targets.Finally,by constructing a protein interaction network,a total of 15 key genes in the network may be screened according to node degree,which may be closely related to the occurrence of gastric cancer.3 Conclusion1.Based on the bioinformatics method,a modular network and a ceRNA regulatory network for the expression of gastric cancer were successfully constructed,which provided a theoretical basis for the pathogenesis of gastric cancer.2.A total of 8 modules related to the pathological T stage of gastric cancer were obtained by WGCNA analysis.The genes in the red module most relevant to pathological T stage were mainly involved in tumor and immune-related pathways and functions,it is believed that the genes in the red module may affect the T stage of gastric cancer by regulating the immune activity of the body or tumor,and participate in the development of gastric cancer.3 Furthermore,by setting the gene significance(GS)and module identity(MM)thresholds,the five most important pivot genes HAVCR2,CYBB,LAIR1,SLAMF8,and CD86 were successfully screened from the red module.These five genes are mainly related to tumor immune activity.Relatedly,it may participate in the development of gastric cancer by mediating the immune response of gastric cancer and provide a potential molecular target for the treatment of gastric cancer.4.Based on the results of WGCNA analysis and comprehensive bioinformatics methods,this study successfully constructed a gastric cancer-specific ceRNA regulatory network,which contains 6 lncRNAs,10 miRNAs,and 44 target mRNAs,providing a theoretical basis for the study of gastric cancer ceRNA laboratory.5.lncRNAPVT1,miR-96,miR-137,miR-145,ANGPT2,SERPINE1,CHEK1,CDC25A are not only included in the ceRNA network,but also related to the prognosis of patients with gastric cancer.It is reported that these 8 key RNAs may play an important role in gastric cancer through ceRNA regulatory network.It can be used as a new potential therapeutic target and a molecular target for predicting the prognosis of gastric cancer.