Screening And Analysis Of Differentially Expressed Genes In Young Breast Cancer Based On Bioinformatics

objective: Because of the special and unique biological behavior of young breast cancer,it is facing considerable challenges for its diagnosis and treatment.Therefore,this study used bioinformatics methods and related software to screen differentially expressed genes in young breast cancer,and then analyzed and verified them.Hope to provide some new perspectives and ideas for further study of young breast cancer.Methods: The young breast cancer and non-young breast cancer related gene microarray data were retrieved from NCBI’s Gene Expression Omnibus(GEO)database.The relevant differentially expressed genes were screened by R4.1.2 software,and the online analysis tool(Web Gestalt)was used to conduct the enrichment analysis of related gene functions and signal pathways in DEGs.Meanwhile,a protein-protein interaction(PPI)was constructed from the String online database and Cytohubba plug-in was used to score the genes in the network and screen out the hub genes.Prognostic value of key genes was assessed using Kaplan-Meier online plotter survival analysis tools.Tumor tissues in TCGA data were grouped according to age as standard,and the expression of prognostic pivotal genes in each age group was analyzed and compared with the expression in normal tissues to verify the obtained pivotal genes.Finally,the clinical specimens were collected and the expression level of LIPE in normal breast tissues,young breast cancer tissues and non-young breast cancer tissues was detected by immunohistochemistry.Results: The gene microarray data sets numbered GSE89116,GSE109169,GSE36295 were screened.according to the parameters and related tools,80 differential genes were screened out,among which 17 were up-regulated and 63 were down-regulated.Enrichment analysis showed that The main biological processes of up-regulated differentially expressed gene enrichment include maintaining the localization of proteins in organelles,homologous tetramerization of proteins and biological regulation;The main cellular components include fibrous collagen trimer,ribbon collagen fibril and collagen trimer complex;The main molecular functions include regulating the activity of double stranded DNA deoxyribonuclease,synthesizing the structural components of extracellular matrix and binding of nucleotides.The main biological processes of down regulating the enrichment of differentially expressed genes include the regulation of lipid metabolism,the response of cells to endogenous stimuli and the response of cells to exogenous stimuli;The main cellular components include multivesicular lumen,plasma membrane and lipid droplets;The main molecular functions include regulating the activity of amino oxidase,the binding of transforming growth factors and the binding of sugars.The main pathways of down regulating the enrichment of differentially expressed genes are phenylalanine metabolism,PPAR signaling pathway and pyruvate metabolism.PPAR signal pathway and AMPK signal pathway are considered to have zero false positive rate.The main key genes found in PPI are PPARG,ADIPOQ,LIPE,PCK1,PDK4,ACACB,PLIN1,CAV1,CD36 and ANGPTL4.The low expression of ACACB,ADIPOQ,LIPE,CAV1,PLIN1 and PPARG genes were associated with the adverse survival in breast cancer patients(HR=0.69、0.84、0.88、0.76、0.78、0.82;95%CI:0.59～0.80、0.76～0.93、0.79～0.97、0.67～0.83、0.70～0.86、0.73～0.90).The expression of six hub genes related to prognosis,ADIPOQ,LIPE,PPARG,PLIN1,CAV1 and ACACB,in normal tissues were much higher than that in tumor tissues of all age groups(H=179.57、161.85、103.62、189.87、118.56、104.03;P<0.001).The expression levels of LIPE and PLIN1 in the young breast cancer group(21～40y)were lower than those in the 41～60 and 61～80 age groups(P<0.05).The protein expression level of LIPE in normal breast tissues was much higher than that in breast cancer tissues(P<0.001),but no significant difference was found in the comparison between young breast cancer tissues and non-young breast cancer tissues.The protein expression of PLIN1 in normal breast tissues was much higher than that in breast cancer tissues(P<0.001),and the protein expression in non-young breast cancer tissues was higher than that in young breast cancer(P<0.05).Conclusion:1.There is a differential gene expression profile between young breast cancer and non-young breast cancer.2.LIPE and PLIN1 may be the key genes for the occurrence and development of early-onset breast cancer.3.The protein expression level of LIPE in normal breast tissue is much higher than that in breast cancer tissue.4.The protein expression of PLIN1 in normal breast tissues is much higher than that in breast cancer tissues,and the protein expression in non-young breast cancer tissues is higher than that in young breast cancer tissues.