The Correlation Between Expression Of P4HA2 And The Prognosis Of Survival In Breast Cancer

Objective:Prolyl 4-hydroxylase subunit alpha 2(P4HA2)is a subtype 2 of prolyl 4-hydroxylases(P4HS).This study analyzed the data of P4HA2 expression and clinical data of breast cancer patients in public database,combined with laboratory experiments,to explore the relationship between P4HA2 expression and survival prognosis of breast cancer patients,and to explore its mechanism.Method:The clinical data and RNA sequencing(RNA-Seq)data of 1090 breast cancer patients were downloaded from the TCGA database,and the difference of P4HA2 expression between breast cancer tissues and normal breast tissues was analyzed.The best cut-off value of P4HA2 in TCGA database breast cancer samples was determined by receiver operating characteristic(ROC)curve.According to the cut-off value,TCGA breast cancer samples were divided into P4HA2 high expression group and low expression group.The area under the ROC curve(AUC)can reflect the diagnostic efficiency of P4HA2 for breast cancer.Chi square test was used to detect the expression of P4HA2 and clinicopathological characteristics of breast cancer patients.The correlation between P4HA2 expression and the expression of P4HA2 was verified by sub group analysis.The Kaplan-Meier curve was drawn,and the relationship between the expression of P4HA2 and the survival of breast cancer patients was analyzed by Log-Rank test.GEO database was used to verify the difference of P4HA2 expression in breast cancer tissues and normal breast tissues and its relationship with the survival of breast cancer patients.HPA database was used to verify the difference of P4HA2 expression in breast cancer tissue and normal breast tissue at protein level.The difference of expression of P4HA2 between normal mammary epithelial cell line and breast cancer cell line was verified by laboratory experiments.Based on univariate and multivariate COX regression analysis,we explored whether P4HA2 could be an independent risk factor for poor prognosis in breast cancer patients.Gene Set Enrichment Analysis(GSEA)and gene correlation analysis are used to explore the mechanism of P4HA2 in the progression of breast cancer.Result:TCGA database analysis of 1090 breast cancer samples showed that P4HA2 was upregulated in breast cancer tissues compared with normal or paracancerous tissues.ROC curve analysis showed that the optimal cut-off value of P4HA2 in TCGA breast cancer samples was 2982.5 and AUC was 0.759,which had a certain diagnostic efficiency.Box plot analysis and chi square test showed that the differential expression of p4ha2 was related to some clinicopathological features.Survival analysis revealed that P4HA2 patients with high expression of breast cancer had poor survival.GEO database confirmed that P4HA2 was upregulated in breast cancer and correlated with poor survival of breast cancer patients.The HPA database confirmed that P4HA2 expression in breast cancer tissues was higher than that in normal breast tissues at protein level.RT-q PCR results showed that the expression of P4HA2 in breast cancer cell line MDA-MB-231 was significantly higher than that in normal breast epithelial cell line MCF-10 A.COX regression analysis suggested that P4HA2 could be an independent risk factor for poor prognosis in breast cancer patients.Gene enrichment analysis and gene correlation analysis showed that P4HA2 may promote the progression of breast cancer through aerobic glycolysis,HIF-1 activation,hypoxia related gene activation,ECM remodeling and Epithelial-mesenchymal transition(EMT)pathway.Conclusion:The expression level of P4HA2 in breast cancer tissue is higher than that in normal breast tissue,which is a potential diagnostic index.Up regulation of P4HA2 is an independent risk factor for poor prognosis in breast cancer patients.P4HA2 is a potential prognostic indicator for breast cancer patients,especially triple-negative breast cancer patients.It is a potential guideline for individualized treatment.P4HA2 may promote breast cancer progression through aerobic glycolysis,HIF-1 activation,hypoxia related gene activation,ECM remodeling,and EMT pathway,or may be potential therapeutic targets.