Prognostic Value of HIF1A-AS3 in Breast cancer

Abstract Breast cancer (BC) is the predominant malignant tumor among women globally. It has high recurrence which have adverse effects on patient outcomes. Therefore, there is need to identify effective biomarkers for prognostic evaluation. Numerous long non-coding RNAs (lncRNAs) have been shown to be implicated in the regulation of different stages of BC tumorigenesis. The role of lncRNA hypoxia-inducible factor 1 alpha-antisense RNA 3 (HIF1A-AS3) in BC has not been studied. The purpose of this study was to find a novel biomarker that can guide the formulation of effective treatments. The relationship between HIF1A-AS3 and BC was explored using the Breast Cancer on The Cancer Genome Atlas (TCGA-BRCA) database. The expression level of HIF1A-AS3 in various BC cells and normal breast cell, BC and paracancerous tissues from clinical patient samples, as well as primary breast cancer cell, respectively was analyzed. The R package was used to analyze RNA sequencing data and identify the differentially expressed genes (DEGs) between BC tissues with high and low expression of HIF1A-AS3 from the TCGA-BRCA database. Kaplan-Meier (KM) and Cox regression analyses were used in the current study to find the predictive value of HIF1A-AS3 on clinical outcomes in patients with BC. The association between infiltration of HIF1A-AS3 and immune cells was determined through Spearman's correlation analyses. The results revealed that the expression of HIF1A-AS3 was significantly elevated in breast cancer cell, BC tissues and primary breast cancer cell compared with that in normal breast cell, paracancerous tissues, and primary breast epithelial cell. KM analysis showed that high expression of HIF1A-AS3 was associated with poor OS [hazard ratio (HR): 1.42, P = 0.029], progression-free interval (PFS) (HR: 1.60, P = 0.005), and DSS (HR: 1.60, P = 0.031), especially in elderly patients below the age of 60, clinical T stage T1 and T2 as well as pathological stages III and IV. This suggested that higher HIF1A-AS3 expression levels were associated with unfavorable prognosis in BC. Moreover, analysis of immune infiltration showed that HIF1A-AS3 expression was associated with some types of immune infiltrating cells. The study identified that HIF1A-AS3 is a potential prognostic biomarker in BC.