Beatriz C Lopes1, Cristine Z Braga2, Fabrício V Ventura2, Jéssica G de Oliveira2, Edson M Kato-Junior2, Newton A Bordin-Junior3, Debora A P C Zuccari1,2,4. 1. Institute of Biosciences, Letters and Exact Sciences (IBILCE), Sao Jose do Rio Preto, Sao Paulo 15054-000, Brazil. 2. Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), Sao Jose do Rio Preto, Sao Paulo 15090-000, Brazil. 3. Hospital de Base de Sao Jose do Rio Preto, Sao Jose do Rio Preto, Sao Paulo 15090-000, Brazil. 4. Laboratory of Molecular Investigation of Cancer (LIMC), Avenue Brigadeiro Faria Lima, 5416, Vila Sao Pedro, Sao Jose do Rio Preto, Sao Paulo 15090-000, Brazil.
Abstract
Detecting circulating microRNAs (miRNAs; miRs) by means of liquid biopsy is an important tool for the early diagnosis and prognosis of breast cancer (BC). We aimed to identify and validate miR-210 and miR-152 as non-invasive circulating biomarkers, for the diagnosis and staging of BC patients, confirming their involvement in tumor angiogenesis. METHODS: RT-qPCR was performed and MiRNA expression analysis was obtained from plasma and fragments of BC and benign breast condition (BBC) women patients, plus healthy subjects. Additionally, the immunohistochemistry technique was carried out to analyze the expression of target proteins. RESULTS: Tumor fragments showed increased expression of oncomiR-210 and decreased expression of miR-152 tumoral suppressor. Both miRNAs were increased in plasma samples from BC patients. The receiver operating characteristic (ROC) curve analysis revealed that only the expression of oncomiR-210 in tissue samples and only the expression of the miR-152 suppressor in plasma have the appropriate sensitivity and specificity for use as differential biomarkers between early/intermediate and advanced stages of BC patients. In addition, there was an increase in the expression of hypoxia-inducible factor 1-alpha (HIF-1α), insulin-like growth factor 1 receptor (IGF-1R), and vascular endothelial growth factor (VEGF) in BC patients. On the contrary, a decrease in Von Hippel-Lindau (VHL) protein expression was observed. CONCLUSIONS: This study showed that increased levels of miR-210 and decreased levels of miR152, in addition to the expressions of their target proteins, could indicate, respectively, the oncogenic and tumor suppressive role of these miRNAs in fragments. Both miRNAs are potential diagnostic biomarkers for BC by liquid biopsy. In addition, miR-152 proved to be a promising biomarker for disease staging.
Detecting circulating microRNAs (miRNAs; miRs) by means of liquid biopsy is an important tool for the early diagnosis and prognosis of breast cancer (BC). We aimed to identify and validate miR-210 and miR-152 as non-invasive circulating biomarkers, for the diagnosis and staging of BC patients, confirming their involvement in tumor angiogenesis. METHODS: RT-qPCR was performed and MiRNA expression analysis was obtained from plasma and fragments of BC and benign breast condition (BBC) womenpatients, plus healthy subjects. Additionally, the immunohistochemistry technique was carried out to analyze the expression of target proteins. RESULTS:Tumor fragments showed increased expression of oncomiR-210 and decreased expression of miR-152tumoral suppressor. Both miRNAs were increased in plasma samples from BC patients. The receiver operating characteristic (ROC) curve analysis revealed that only the expression of oncomiR-210 in tissue samples and only the expression of the miR-152 suppressor in plasma have the appropriate sensitivity and specificity for use as differential biomarkers between early/intermediate and advanced stages of BC patients. In addition, there was an increase in the expression of hypoxia-inducible factor 1-alpha (HIF-1α), insulin-like growth factor 1 receptor (IGF-1R), and vascular endothelial growth factor (VEGF) in BC patients. On the contrary, a decrease in Von Hippel-Lindau (VHL) protein expression was observed. CONCLUSIONS: This study showed that increased levels of miR-210 and decreased levels of miR152, in addition to the expressions of their target proteins, could indicate, respectively, the oncogenic and tumor suppressive role of these miRNAs in fragments. Both miRNAs are potential diagnostic biomarkers for BC by liquid biopsy. In addition, miR-152 proved to be a promising biomarker for disease staging.
Entities:
Keywords:
angiogenesis; biomarkers; breast cancer; early diagnosis; liquid biopsy; miRNAs
Authors: Carina Roth; Brigitte Rack; Volkmar Müller; Wolfgang Janni; Klaus Pantel; Heidi Schwarzenbach Journal: Breast Cancer Res Date: 2010-11-03 Impact factor: 6.466