Abeer Bahnassy1, Marwa Mohanad2, Manal F Ismail3, Sabry Shaarawy4, Ahmed El-Bastawisy5, Abdel-Rahman N Zekri4. 1. Molecular Pathology Unit, Pathology Department, National Cancer Institute, Cairo University, Egypt. Electronic address: chaya2000@hotmail.com. 2. Department of Biochemistry, Faculty of Pharmacy, Misr University for Science and Technology, Egypt. 3. Department of Biochemistry, Faculty of Pharmacy, Cairo University, Egypt. 4. Department of Cancer Biology, National Cancer Institute, Cairo University, Egypt. 5. Department of Medical Oncology, National Cancer Institute, Cairo University, Egypt.
Abstract
BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive phenotype of breast cancer with reduced survival and poor prognosis. Increased VEGF-A, IGF-I, IGF-IR and TGF-β1 expressions were detected in breast cancer. However, little is known about their prognostic and predictive roles in TNBC. AIM: We assessed the possible prognostic and predictive values of VEGF-A, IGF-I/IGF-IR and TGF-β1 in TNBC cases by measuring their protein and mRNA expression in TNBC and non-TNBC cases. METHODS: VEGF-A, IGF-I, IGF-IR and TGF-β1 RNA and their corresponding proteins were assessed in 43 TNBCs, 53 non-TNBCs and 30 normal breast tissues (NBT) by real time PCR (qPCR) and immunohistochemistry (IHC); respectively. Results were related to clinico-pathological factors, response to treatment and survival rates. RESULTS: Increased mRNA expression of VEGF-A, IGF-I, and IGF-IR was significantly higher in TNBC (65.1%, 65.1%, and 72.1%) than non-TNBC (28.1%, 33.96% and 28.3%) and NBT (0.00%) (P<0.001). Similarly, TNBC patients were significantly associated with high expression of VEGF-A, IGF-I, and IGF-IR proteins (67.44%, 62.79% and 83.72%) than non-TNBC (20.75%, 35.86% and 20.75%) and NBT (0.00%) (P<0.001). Protein and RNA expression levels of all studied markers showed high concordance in all investigated patients (correlation coefficient exceeding 0.5 and 0.4, respectively). In the TNBC group, metastasis and poor response to treatment were significantly associated with VEGF-A (P<0.001, P=0.007, respectively), IGF-I (P<0.001, P<0.001, respectively), IGF-IR (P=0.001, P=0.015, respectively) and TGF-β1 (P<0.001, P=0.007, respectively) protein levels. Multivariate logistic regression showed that IGF-I was the only independent prognostic factor for reduced OS (P=0.034) and DFS (P=0.026) in the TNBC patients. CONCLUSIONS: VEGF-A, IGF-I and IGF-IR play an important role in the development and progression of TNBC compared to non-TNBC. Therefore, they could be used as prognostic and predictive biomarkers as well as candidates for targeted therapy. However, only IGF-I can predict survival in those patients.
BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive phenotype of breast cancer with reduced survival and poor prognosis. Increased VEGF-A, IGF-I, IGF-IR and TGF-β1 expressions were detected in breast cancer. However, little is known about their prognostic and predictive roles in TNBC. AIM: We assessed the possible prognostic and predictive values of VEGF-A, IGF-I/IGF-IR and TGF-β1 in TNBC cases by measuring their protein and mRNA expression in TNBC and non-TNBC cases. METHODS:VEGF-A, IGF-I, IGF-IR and TGF-β1 RNA and their corresponding proteins were assessed in 43 TNBCs, 53 non-TNBCs and 30 normal breast tissues (NBT) by real time PCR (qPCR) and immunohistochemistry (IHC); respectively. Results were related to clinico-pathological factors, response to treatment and survival rates. RESULTS: Increased mRNA expression of VEGF-A, IGF-I, and IGF-IR was significantly higher in TNBC (65.1%, 65.1%, and 72.1%) than non-TNBC (28.1%, 33.96% and 28.3%) and NBT (0.00%) (P<0.001). Similarly, TNBC patients were significantly associated with high expression of VEGF-A, IGF-I, and IGF-IR proteins (67.44%, 62.79% and 83.72%) than non-TNBC (20.75%, 35.86% and 20.75%) and NBT (0.00%) (P<0.001). Protein and RNA expression levels of all studied markers showed high concordance in all investigated patients (correlation coefficient exceeding 0.5 and 0.4, respectively). In the TNBC group, metastasis and poor response to treatment were significantly associated with VEGF-A (P<0.001, P=0.007, respectively), IGF-I (P<0.001, P<0.001, respectively), IGF-IR (P=0.001, P=0.015, respectively) and TGF-β1 (P<0.001, P=0.007, respectively) protein levels. Multivariate logistic regression showed that IGF-I was the only independent prognostic factor for reduced OS (P=0.034) and DFS (P=0.026) in the TNBC patients. CONCLUSIONS:VEGF-A, IGF-I and IGF-IR play an important role in the development and progression of TNBC compared to non-TNBC. Therefore, they could be used as prognostic and predictive biomarkers as well as candidates for targeted therapy. However, only IGF-I can predict survival in those patients.
Authors: Danielle Bogan; Lucio Meile; Ahmed El Bastawisy; Hend F Yousef; Abdel-Rahman N Zekri; Abeer A Bahnassy; Wael M ElShamy Journal: BMC Cancer Date: 2017-05-12 Impact factor: 4.430
Authors: Abhilasha Sinha; Bibbin T Paul; Lisa M Sullivan; Hillary Sims; Ahmed El Bastawisy; Hend F Yousef; Abdel-Rahman N Zekri; Abeer A Bahnassy; Wael M ElShamy Journal: Oncotarget Date: 2017-02-07
Authors: Maryam Nakhjavani; Jennifer E Hardingham; Helen M Palethorpe; Tim J Price; Amanda R Townsend Journal: J Breast Cancer Date: 2019-09-02 Impact factor: 3.588
Authors: Danylo Rafhael Costa-Silva; Maria da Conceição Barros-Oliveira; Francisco Adelton Alves-Ribeiro; Larysse Cardoso Campos-Verdes; Elmo de Jesus Nery Junior; Samara Fernanda Vieira-Valença; Rodrigo Jose de Vasconcelos-Valença; Veronica Mendes Soares; André Luiz Pinho-Sobral; Emerson Brandão Sousa; Pedro Vitor Lopes-Costa; Alesse Ribeiro Dos Santos; Jackeline Lopes Viana; Arquimedes Cavalcante Cardoso; Victoria Maria Luz-Borges; Renato de Oliveira Pereira; Cleciton Braga Tavares; Vladimir Costa Silva; Dorival Mendes Rodrigues-Junior; Luiz Henrique Gebrim; Benedito Borges da Silva Journal: Medicine (Baltimore) Date: 2020-10-23 Impact factor: 1.817