Serum Free HIF-1A RNA Level Correlation with Carbonic Anhydrase CAIX Patterns in Different Grade and Treatment Status of Breast Cancer

Abstract

Breast cancer is a complex disease that has many different molecular subtypes and the most Tumor cells use several adaptations, such as carbonic anhydrase (CAIX) and hypoxia-inducible factor 1-alpha (HIF-1α), to survive and proliferate in hypoxic environments. This study aims to investigate the role of Carbonic anhydrase 9 (CAIX) in breast cancer and correlation with HIF1A gene expression. Different assay used in this research included RT-qPCR (Quantitative reverse transcription polymerase chain reaction) for HIF1A expression and the ELISA (Enzyme-linked immunosorbent Assay) technique for measuring CAIX activity.  The study included 100 newly diagnosed cases of BC divided in to four groups. There were twenty-five patients with low grade of Bc before treatment (LBT) and twenty-five patients with low grade of Bc after treatment (LAT). The remaining twenty-five patients with high grade of Bc before treatment (HBT) and twenty-five patients with high grade of Bc after treatment (HAT). There were fifteen health individuals in the control group. After sample collection, the blood sample divided in to two aliquots. One for RNA extraction, cDNA synthesis and serum sample for CAIX measurement. The results of this research with area under the curve (AUC), showed HIF-1α expression with (AUC= 0.77) in high grade before treatment and AUC=0.6) in high grade after treatment. Other types of samples display (AUC< 0.4) indicate low diagnostic accuracy. CA9 showed exhibited moderate diagnostic result with (AUC=0.6) in high grade after treatment, others showed AUC <0.5). Furthermore, increasing median BMI and age group showed moderate significance with HIF-1α and CA9 expression in all experimental groups.  The correlation analysis between HIF-1α, CA9 and control group displayed no significance for all experimental groups (p>0.05).