Abstract
Background Breast cancer is the commonest malignancy in women worldwide. It is estimated to affect approximately 1.5 million women annually and responsible for the greatest number of cancer-related mortalities among women. In 2018, breast cancer mortalities stood at 627,000 women representing approximately 15% of all cancer deaths among women. In Ghana, breast cancer is the second leading cause of cancer deaths, with an incidence of 2,900 cases annually; one of eight women with the disease die. This gives impetus to the fight for improved early detection, treatment, and/management. In this light, we investigated the potential of death-associated protein kinase 1 (DAPK1) as a biomarker for breast cancer. As a tumour suppressor, its expression is activated by several carcinogens to influence cellular pathways that result in apoptosis, autophagy, immune response, and proliferation. Aim To investigate DAPK1 as a blood biomarker for breast cancer. Methods Blood samples of participants diagnosed with breast cancer and healthy controls were collected and processed to obtain serum. Information on age, treatment, diagnosis, and pathology numbers was retrieved from folders. Pathology numbers were used to retrieve breast tissue blocks of patients at the Department of Pathology of the KBTH. Tissue blocks were sectioned and immunohistochemically stained with anti-DAPK1 and counterstained with hematoxylin to determine the DAPK1 expression levels. DAKP1 levels in blood sera were quantified using a commercial anti-DAPK1 ELISA kit. Case and control group means were compared using one-way ANOVA and Chi-square test. Statistical significance was set at p ≤ 0.05. Results and Discussion. DAPK1 levels were higher in sera and breast tissues of breast cancer patients than controls. The augmented DAPK1 expression can be interpreted as a stress response survival mechanism to remediate ongoing deleterious events in the cells orchestrated by carcinogenesis. In the presence of abundant DAPK1, the proliferative power of cells (both cancerous and noncancerous) is increased. This may explain why high DAPK1 expression strongly associates with aggressive breast cancer phenotypes like the ER-negative breast cancers, especially the triple-negative breast cancers (TNBC) which are the most aggressive, fast-growing, and highly metastatic. Conclusion DAPK1 is highly expressed in sera and breast tissues of breast cancer patients than nonbreast cancer participants. The elevated expression of DAKP1 in circulation rather than in breast tissues makes it a candidate for use as a blood biomarker and potential use as therapeutic target in drug development.
Highlights
The World Health Organisation (WHO) report for 2018 indicates that cancer is the second leading cause of death globally accounting for 9.6 million deaths and further state that nearly 1 in 6 deaths globally is due to cancer with about 70% of these deaths occurring in low- and middle-income countries [1]
We have previously reported that death-associated protein kinase 1 (DAPK1) was elevated in archived serum samples of breast cancer patients compared to nonbreast cancer individuals and the protein was associated with aggressive breast tumour phenotypes in Ghanaians [23]
We report that DAPK1 expression levels in both sera and breast tissue samples are higher in breast cancer patients than in their nonbreast cancer counterparts
Summary
The World Health Organisation (WHO) report for 2018 indicates that cancer is the second leading cause of death globally accounting for 9.6 million deaths and further state that nearly 1 in 6 deaths globally is due to cancer with about 70% of these deaths occurring in low- and middle-income countries [1]. Breast cancer prevalence and mortality rates are seeing worryingly increasing trends in women in most regions of the globe This is a departure from what historically used to be restricted to women in the more developed regions of the world [4]. In Ghana, breast cancer is the second leading cause of cancer deaths, with an incidence of 2,900 cases annually; one of eight women with the disease die. This gives impetus to the fight for improved early detection, treatment, and/management. DAPK1 levels were higher in sera and breast tissues of breast cancer patients than controls. DAPK1 is highly expressed in sera and breast tissues of breast cancer patients than nonbreast cancer participants. The elevated expression of DAKP1 in circulation rather than in breast tissues makes it a candidate for use as a blood biomarker and potential use as therapeutic target in drug development
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