Expression And Clinical Significance Of LDHA And HIF-1α In Breast Cancer

Objective:One of the hallmark of cancer is the metabolic reprogramming of cancer cells,which has led to a growing interest in targeted cell metabolism as a potential approach to cancer treatment.Breast cancer is a highly heterogeneous and complex metabolic disease,which reconstitutes cell metabolism mainly through Warburg effect.LDHA and HIF-1 α are important driving factors of metabolic reprogramming in breast cancer and play key roles in the proliferation,migration,acidic microenvironment formation,immune escape and other aspects of breast cancer.Therefore,targeting the metabolism of breast cancer cells may be a promising cancer treatment strategy.This study aimed to detect the expression of LDHA and HIF-1α protein in breast cancer by immunohistochemical method,to explore the significance and significance of LDHA and HIF-1α in the occurrence and development of breast cancer,and to verify whether LDHA and HIF-1α could be a new target for the clinical diagnosis,treatment and prognosis of breast cancer.Methods:This study aimed to investigate the expression levels of LDHA and HIF-1α in invasive breast cancer patients who underwent breast surgery at Shanxi Provincial People’s Hospital between June 2015 and December 2015.Ninety-six patients with invasive breast cancer were selected,and their corresponding paracancerous tissue was used as a control.Immunohistochemistry was used to detect the expression levels of LDHA and HIF-1α in BC.The DFS and OS of the patients were tracked by telephone and outpatient follow-up,and the relationship between the expressions of LDHA and HIF-1α,clinicopathological features and survival prognosis was analyzed statistically using SPSS28.0 software.The intergroup analysis was performed using the chi-square test,and statistical significance was set at(p< 0.05).The data were also analyzed using Spearman correlation analysis.Furthermore,prognosis was analyzed using Kaplan-Meier and the log-rank test.Results:1.LDHA expression: LDHA was expressed in cytoplasm or nucleus.The high expression of LDHA in BC was 67.7%(65/96).The high expression of LDHA in BC was significantly higher than that in adjacent control tissues 18.8%(18/96)(p < 0.001).2.HIF-1α expression: HIF-1α was expressed in cytoplasm or nucleus.The high expression of HIF-1α was 58.3%(56/96)in BC.The high expression of HIF-1α in cancer tissue was significantly higher than that of in adjacent control tissue25.0%(24/96)(p<0.001).3.Correlation between LDHA and HIF-1α expression: Spearman correlation test showed that LDHA and HIF-1α were positively correlated(r=0.456,p<0.001).4.The relationship with different pathological factors: The high expression of LDHA and HIF-1α in breast cancer was found to be related to clinical stage,Ki-67 expression status,histological grade,and axillary lymph node condition(p < 0.05).And the expression of both targets also had relationship with axillary lymph node condition(p<0.05).The high expression of HIF1α was significantly correlated with the low expression of ER and PR and the high expression of HER-2 and Ki-67.The expression of HIF-1α in TNBC and HER-2-positive breast cancer was high(p<0.05).Although the expression of LDHA was no significant different among the molecular types of breast cancer(p>0.05),the expression of LDHA in TNBC was the highest.5.Prognostic analysis of LDHA and HIF-1α in patients with breast cancer: The expression of LDHA was negatively correlated with OS(p=0.028)and DFS(p=0.023).Similarly,the expression of was also negatively correlated with OS and DFS(OS p =0.003,DFS p < 0.001).Conclusion:1.LDHA 、 HIF-1α are up-regulated in breast cancer.They appear to have a synergistic effect in promoting cancer cell proliferation and invasion.2.The expression levels of LDHA and HIF-1α are associated with several clinicopathological factors,including Ki-67 expression status,clinical stage,histological grade,and axillary lymph node metastasis.To some extent,the malignancy of breast cancer can be assessed.Compared to LDHA,HIF-1α It has more important clinical significance in TNBC 、HER-2 positive breast cancer.It may become a new therapeutic target for breast cancer in the future.3.High expressions of HIF1α and LDHA are associated with poor prognosis in BC,may be used as biomarkers to guide clinical prognosis.