Abstract
BackgroundBreast cancer is the second leading cause of cancer related deaths in women worldwide. Reports about the early diagnosis of breast cancer are suggestive of an improved clinical outcome and overall survival rate in cancer patients. Therefore, cancer screening biomarker for early detection and diagnosis is urgently required for timely treatment and better cancer management. In this context, we investigated an association of cancer testis antigen, A-Kinase anchor protein 4 (AKAP4) with breast carcinoma.Methodology/FindingsWe first compared the AKAP4 gene and protein expression in four breast cancer cells (MCF7, MDA-MB-231, SK-BR3 and BT474) and normal human mammary epithelial cells. In addition, 91 clinical specimens of breast cancer patients of various histotypes including ductal carcinoma in situ, infiltrating ductal carcinoma and infiltrating lobular carcinoma and 83 available matched adjacent non-cancerous tissues were examined for AKAP4 gene and protein expression by employing in situ RNA hybridization and immunohistochemistry respectively. Humoral response against AKAP4 was also investigated in breast cancer patients employing ELISA. Our in vitro studies in all breast cancer cells revealed AKAP4 gene and protein expression whereas, normal human mammary epithelial cells failed to show any expression. Using in situ RNA hybridization and immunohistochemistry, 85% (77/91) tissue specimens irrespective of histotypes, stages and grades of breast cancer clinical specimens revealed AKAP4 gene and protein expression. However, matched adjacent non-cancerous tissues failed to display any AKAP4 gene and protein expression. Furthermore, humoral response was observed in 79% (72/91) of total breast cancer patients. Interestingly, we observed that 94% (72/77) of breast cancer patients found positive for AKAP4 protein expression generated humoral response against AKAP4 protein.ConclusionsCollectively, our data suggests that AKAP4 may be used as serum based diagnostic test for an early detection and diagnosis of breast cancer and may be a potential target for immunotherapeutic use.
Highlights
Breast cancer is the most commonly diagnosed cancer and is the second leading cause of cancer related deaths in women worldwide [1]
Collectively, our data suggests that A-Kinase anchor protein 4 (AKAP4) may be used as serum based diagnostic test for an early detection and diagnosis of breast cancer and may be a potential target for immunotherapeutic use
AKAP4 gene expression was investigated in human normal mammary epithelial cells and breast cancer cells of two different origins namely adenocarcinoma (MCF7, MDA-MB-231 and SKBR3), and ductal carcinoma (BT474)
Summary
Breast cancer is the most commonly diagnosed cancer and is the second leading cause of cancer related deaths in women worldwide [1]. Reports on breast cancer have shown that early diagnosis directly contributes to improved clinical outcome and over-all survival in breast cancer patients [2]. Multiple tumor biomarkers have been reported in breast cancer including carcinoembryonic antigen (CEA), mucin 1 (MUC1) and CA 15-3 [3]. None of these biomarkers have been implicated in clinical practice because of false-positive rate in normal populations, and low diagnostic sensitivity and specificity [3]. Cancer screening biomarker for early detection and diagnosis is urgently required for timely treatment and better cancer management In this context, we investigated an association of cancer testis antigen, A-Kinase anchor protein 4 (AKAP4) with breast carcinoma
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