Circulating cell-free DNA integrity as a diagnostic and prognostic marker for breast and prostate cancers

Benjamin Arko-Boham; Nii Ayite Aryee; Richard Michael Blay; Ewurama Dedea Ampadu Owusu; Emmanuel Ayitey Tagoe; Eshirow-Sam Doris Shackie; Ama Boatemaa Debrah; Nii Armah Adu-Aryee

doi:10.1016/j.cancergen.2019.04.062

Circulating cell-free DNA integrity as a diagnostic and prognostic marker for breast and prostate cancers

Cancer Genet. 2019 Jun:235-236:65-71. doi: 10.1016/j.cancergen.2019.04.062. Epub 2019 Apr 23.

Authors

Benjamin Arko-Boham¹, Nii Ayite Aryee², Richard Michael Blay³, Ewurama Dedea Ampadu Owusu⁴, Emmanuel Ayitey Tagoe⁵, Eshirow-Sam Doris Shackie⁶, Ama Boatemaa Debrah⁶, Nii Armah Adu-Aryee⁷

Affiliations

¹ Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana; Department of Anatomy, School of Biomedical and Allied Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana. Electronic address: barko-boham@ug.edu.gh.
² Department of Medical Biochemistry, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana.
³ Department of Anatomy, School of Biomedical and Allied Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana.
⁴ Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana; Centre of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Centre, University of Amsterdam, Postbus 226601100 DD Amsterdam, the Netherlands; Foundation for Innovative and New Diagnostics (FIND), 9 Chemin des Mines, 1202, Geneva, Switzerland.
⁵ Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana; West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, P.O. Box LG 25, Legon, Accra, Ghana.
⁶ Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana.
⁷ Department of Surgery, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, P.O. Box KB 143, Korle-Bu, Accra, Ghana; Department of Surgery, Korle-Bu Teaching Hospital, P.O. Box, 77 Accra, Ghana.

PMID: 31105051
DOI: 10.1016/j.cancergen.2019.04.062

Abstract

Background: Cancer incidence and its related mortality is rising and is currently the second leading cause of death globally. In Africa, breast and prostate cancer in females and males, respectively, are the worst globally. However, biomarkers for their early detection and prognosis are not well developed. This study sought to investigate circulating cell-free DNA (ccfDNA) integrity and its potential utility as diagnostic and/or prognostic biomarker. Circulating cell-free DNA (ccfDNA) is degraded DNA fragments released into the blood plasma. In healthy individuals, the source of ccfDNA is solely apoptosis, producing evenly sized shorter DNA fragments. In cancer patients, however, necrosis produces uneven longer cell-free DNA fragments in addition to the shorter fragments originating from apoptosis. DNA integrity, expressed as the ratio of longer fragments to total DNA, may be clinically useful for the detection of breast and prostate cancer progression.

Methods: Sixty-four (64) females, consisting of 32 breast cancer patients and 32 controls, and 61 males (31 prostate cancer patients and 30 controls) were included in the study. Each participant donated 5 ml peripheral blood from which sera were separated. Real-time qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) determined.

Results & conclusion: ALU species 115 and 247 levels in serum were elevated in breast and prostate cancer patients compared to their counterpart healthy controls. DNA integrity was higher in prostate cancer patients than in the control, but in breast cancer patients was lower compared to their controls. In prostate but not in breast cancers, DNA integrity increased with disease severity and higher staging.

Keywords: Breast cancer; Circulating cell-free DNA; DNA integrity; Prostate cancer.

MeSH terms

Adult
Aged
Alu Elements / genetics
Biomarkers, Tumor / blood
Breast Neoplasms / blood*
Breast Neoplasms / diagnosis
Breast Neoplasms / genetics
Cell-Free Nucleic Acids / blood*
Cell-Free Nucleic Acids / genetics
DNA, Neoplasm / blood*
Disease Progression
Early Detection of Cancer / methods*
Female
Humans
Male
Middle Aged
Prognosis
Prostatic Neoplasms / blood*
Prostatic Neoplasms / diagnosis
Prostatic Neoplasms / genetics
Real-Time Polymerase Chain Reaction

Substances

Biomarkers, Tumor
Cell-Free Nucleic Acids
DNA, Neoplasm