TY - JOUR
T1 - Prospecting for Breast Cancer Blood Biomarkers
T2 - Death-Associated Protein Kinase 1 (DAPK1) as a Potential Candidate
AU - Arko-Boham, Benjamin
AU - Owusu, Bright Afriyie
AU - Aryee, Nii Ayite
AU - Blay, Richard Michael
AU - Owusu, Ewurama Dedea Ampadu
AU - Tagoe, Emmanuel Ayitey
AU - Adams, Abdul Rashid
AU - Gyasi, Richard Kwasi
AU - Adu-Aryee, Nii Armah
AU - Mahmood, Seidu
N1 - Publisher Copyright:
© 2020 Benjamin Arko-Boham et al.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85086656187&partnerID=8YFLogxK
U2 - 10.1155/2020/6848703
DO - 10.1155/2020/6848703
M3 - Article
C2 - 32566040
AN - SCOPUS:85086656187
SN - 0278-0240
VL - 2020
JO - Disease Markers
JF - Disease Markers
M1 - 6848703
ER -