Diagnostic potential of hypoxia-induced genes in liquid biopsies of breast cancer patients

Abstract

In tumor cells, higher expression of glucose transporter proteins (GLUT) and carbonic anhydrases (CAIX) genes is influenced by hypoxia-induced factors (HIF).Thus, we aimed to study the expression profile of these markers in sequential peripheral blood collections performed in breast cancer patients in order to verify their predictive potential in liquid biopsies. Gene expressions were analyzed by qPCR in tumor and blood samples from 125 patients and 25 healthy women. Differential expression was determined by the 2(−ΔCq) method. Expression of HIF-1α and GLUT1 in the blood of breast cancer patients is significantly higher (90–91 and 160–161 fold increased expression, respectively; p < 0.0001) than that found in healthy women. Their diagnostic power was confirmed by ROC curve. CAIX is also more expressed in breast cancer women blood, but its expression was detected only in a few samples. But none of these genes could be considered predictive markers. Therefore, evaluation of the expression of HIF-1α and GLUT1 in blood may be a useful laboratory tool to complement the diagnosis of breast cancer, in addition to being useful for follow-up of patients and of women with a family history of breast cancer.

Exploring the Role of Hypoxia-Inducible Carbonic Anhydrase IX (CAIX) in Circulating Tumor Cells (CTCs) of Breast Cancer

“…The theoretical cell surface protein panel consisted of proteins associated with cell–cell junctions (GJA1 and RND1) and those that survive in hypoxic conditions (CA9, GLUT1, and SLC6A6). Studies have shown that CAIX is overexpressed in hypoxic tumors and may co-localize with GLUT1, a HIF1α-induced nutrient transporter that is being studied in liquid biopsies for certain types of breast cancer [ 9 , 26 , 27 , 28 ].…”

Primary Duodenal Adenocarcinoma Expressing Carbonic Anhydrase IX

“…Given that studies have recently been conducted to evaluate CA9 expression in blood samples as a potential diagnostic marker for renal cell carcinoma [8] and breast cancer [9] with promising results, CA9 expression in blood samples may have potential as a diagnostic marker for primary duodenal carcinoma as well.…”