Breast cancer therapy affects the expression of antineonatal Nav1.5 antibodies in the serum of patients with breast cancer
| Autor: | Maya Mazuwin Yahya, Nur Syahmina Rasudin, Wan Ezumi Mohd Fuad, Harishini Rajaratinam, Nurul Asma Abdullah, Tengku Ahmad Damitri Al Astani, Wan Zainira Wan Zain, Noor Fatmawati Mokhtar |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Metastasis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Immune system breast cancer Internal medicine Medicine antibodies metastasis breast cancer therapy Oncogene biology business.industry Interleukin Articles medicine.disease Molecular medicine Vascular endothelial growth factor immune system 030104 developmental biology chemistry 030220 oncology & carcinogenesis biology.protein Antibody business neonatal Nav1.5 |
| Zdroj: | Oncology Letters |
| ISSN: | 1792-1082 1792-1074 |
| Popis: | Neonatal Nav1.5 (nNav1.5) is the alternative splice variant of Nav1.5 and it has been widely associated with the progression of breast cancer. The immunological context of nNav1.5 with respect to breast cancer metastases remains unexplored. The presence of antibodies against nNav1.5 may highlight the immunogenicity of nNav1.5. Hence, the aim of the present study was to detect the presence of antineonatal Nav1.5 antibodies (antinNav1.5-Ab) in the serum of patients with breast cancer and to elucidate the effects of breast cancer therapy on its expression. A total of 32 healthy female volunteers and 64 patients with breast cancer were randomly recruited into the present study as the control and breast cancer group, respectively. Patients with breast cancer were divided equally based on their pre- and ongoing-treatment status. Serum samples were tested with in-house indirect enzyme-linked immunosorbent assay (ELISA) to detect antinNav1.5-Ab, CD25 (T regulatory cell marker) using an ELISA kit and Luminex assay to detect the expression of metastasis-associated cytokines, such as vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-10, IL-8, chemokine (C-C motif) ligand 2 and tumor necrosis factor-alpha (TNF-α) The mean difference in the expression of antinNav1.5-Ab among the three groups (control, pretreatment and ongoing-treatment) was significant (P=0.0005) and the pretreatment breast cancer group exhibited the highest expression. The concentration of CD25 was highest in the pretreatment breast cancer group compared with the control and ongoing-treatment groups. There was a significant positive correlation between antinNav1.5-Ab and IL-6 in the pretreatment group (r=0.7260; P=0.0210) and a significant negative correlation between antinNav1.5-Ab and VEGF in the ongoing-treatment group (r=-0.842; P-value=0.0040). The high expression of antinNav1.5-Ab in the pretreatment group was in accordance with the uninterrupted presence of metastasis and highlighted the immunogenicity of nNav1.5 whereas the low expression of antinNav1.5-Ab in the ongoing-treatment group reflected the efficacy of breast cancer therapy in eliminating metastases. The augmented manifestation of T regulatory cells in the pretreatment group highlighted the functional role of nNav1.5 in promoting metastasis. The parallel expression of antinNav1.5-Ab with the imbalanced expression of cytokines promoting metastasis (IL-8, IL-6 and TNF-α) and cytokines that prevent metastasis (IL-10) indicated the role of nNav1.5 in breast cancer growth. The expression of antinNav1.5-Ab in accordance to the metastatic microenvironment indicates the immunogenicity of the protein and highlights the influence of breast cancer therapy on its expression level. |
| Databáze: | OpenAIRE |
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