Analysis And Validation Of GEO Data Of Obesity-related Genes In Postmenopausal Breast Cancer Patients With Estrogen Receptor Positive

Part Ⅰ Analysis and validation of GEO data of obesity-related genes in postmenopausal breast cancer patients with estrogen receptor positiveBackground and objective:Breast cancer is one of the most common malignancies among women in the world today.Obesity can increase the risk of postmenopausal breast cancer.With a 1 unit increase in BMI,the risk of breast cancer in postmenopausal women will increase by 2%.In addition,obesity has a negative impact on the prognosis of premenopausal and postmenopausal patients,but the most significant effect is estrogen receptor-positive postmenopausal patients,a finding confirmed by a retrospective analysis of the German BRENDA cohort.In this study,the breast cancer gene microarray data downloaded from the GEO public database was used to explore obesity and estrogen receptor-positive postmenopausal breast cancer-related genes.Methods:1 Analysis of gene expression dataAfter data preprocessing on the R-based Bioconductor platform,screening for differentially expressed genes,GO(gene ontology)analysis,cluster analysis,and KEGG Pathway analysis were performed.2 Real-time fluorescent quantitative PCRSYBR Real-time fluorescent quantitative PCR was used to detect mRNA expression levels of COL1A2,MMP14,and SLC26A3 in 96 tissue samples.3 Western blottingSix pairs of obesity group and six non-obesity group breast cancer tissue samples were randomly selected to extract total protein for Western blotting.Results:1.Analysis results of gene expression dataFinally,a total of 566 differentially expressed genes were screened out.Obesity estrogen receptor positive postmenopausal breast cancer had 342 genes up-regulated and 224 genes down-regulated.2.Detection of mRNA expression of target genesThe mRNA expression level of COL1A2 gene was up-regulated in 61.4%of breast cancer tissues(59/96,P=0.046)and the relative mRNA expression level in obese group was significantly higher than that in non-obese group(P=0.013).The mRNA expression level of MMP14 gene was up-regulated in 55.2%of the cancer tissues(53/96,P<0.0002)and the relative mRNA expression level in the obese group was significantly higher than that in the non-obese group(P=0.003).The mRNA expression level of SLC26A3 gene was down-regulated in 78.1%of cancer tissues(75/96,P=0.0085)and the relative mRNA expression level in obese group was significantly lower than that in non-obese group(P=0.008).3.Detection of COL1A2 protein expression by Western blottingRelative to paracancerous tissues,the expression of COL1A2 protein was higher in breast cancer tissues;compared with non-obesity group breast cancer tissues,the relative expression of COL1A2 protein in obesity group breast cancer was more high.Conclusion:1.The results of microarray data analysis showed that the differentially expressed genes of obese postmenopausal estrogen receptor-positive breast cancer were mainly related to 23 cell functions such as metallo-peptidase activity and collagen metabolism.KEGG Pathway analysis showed that differentially expressed genes were mainly involved in signal pathways.There are:PDGF signaling pathway,activation of platelet activation and so on.2.The COL1A2 gene may be a obesity and estrogen receptor-positive postmenopausal breast cancer-related gene and potential therapeutic target.Part Ⅱ Detection and clinical application of circulating tumor DNA in breast cancerWith the advancement of detection technology,circulating tumor DNA has a very broad application prospect in the early diagnosis of tumors,prognosis assessment,efficacy and tumor load monitoring.At the same time,breast cancer chemotherapy,targeted therapy and endocrine therapy will be more individualized and targeted.