Study of the integrity of ccfDNA ALU-115, ALU-247 in patients with breast cancer
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Abstract
ccfDNA (cell-free circulating DNA) is free DNA circulating in the blood, originating from dead or damaged cells. ALU-115 and ALU-247 are small DNA fragments that can be used to assess the integrity of ccfDNA, especially in cancer. Therefore, this study aims to investigate the concentration and integrity of ccfDNA ALU-115 and ALU-247, thereby evaluating their role in various clinical and preclinical factors of breast cancer patients. The study used a case-control method with a patient/control ratio of 50/50. The results showed that in the disease group, the average concentration of ALU-115 was 3.37 ± 3.9 ng/mL and ALU-247 was 0.21 ± 0.24 ng/mL, lower than the corresponding control group of 80.46 ± 163.94 ng/mL and 0.87 ± 1.44 ng/mL, respectively. The integrity of ccfDNA (DI) in the disease group was 0.1 ± 0.06, higher than the control group of 0.07 ± 0.08. The average DI was lowest in stage I breast cancer patients compared to the remaining stages (II, III, IV) and tended to increase with the severity and stage of the disease (II, III, IV). The DI of the patient group with ER (+) was lower than the ER (-) group. No correlation was found between the concentration and integrity of ccfDNA ALU-115 and ALU-247 with clinicopathological factors such as regional lymph node characteristics, distant metastasis, disease stage, as well as with proteins CA15-3, ER, PR, HER-2, Ki67. The initial study suggests the integrity of ccfDNA has a potential contribution to monitoring disease progression and treatment response in breast cancer patients . Further research performed on a larger scale is recommended to support this hypothesis.
Article Details
Keywords
Breast cancer, ALU-115, ALU-247, integrity
References
2. Fleischhacker M , Schmidt B , Circulating nucleic acids (CNAs) and cancer-a survey.Biochim Biophys Acta. 2017; 1775: 181-232,
3. Cicchillitti L, Corrado G, De Angeli M, etal. Circulating cell-free DNA content as blood based biomarker in endometrial cancer. Oncotarget. 2017; 8(70): 115230-43.
4. Thakur ZH, Becker A, Matei I, Huang Y, Costa-Silva B, Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Research. 2014; 24(6): 766-9,
5. Stoetzer OJ, Fersching DM, Salat C, Steinkohl O, Gabka CJ, Hamann U, Braun M, Feller AM, Heinemann V, Siegele B, Nagel D, Holdenrieder S, Prediction of response to neoadjuvant chemotherapy in breast cancer patients by circulating apoptotic biomarkers nucleosomes, DNAse, cytokeratin-18 fragments and survivin. Cancer Letters. 2013; 336(1): 140-8,
6. Jahr S, Hentze H, Englisch S, Hardt D, Fackelmeyer FD, Hesch RD, Knippers Rl, DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001; 61: 1659–65,
7. Hussein NA, Mohamed SN, Ahmed MA. Plasma ALU-247, ALU-115, and cfDNA Integrity as Diagnostic and Prognostic Biomarkers for Breast Cancer. Appl Biochem Biotechnol. 2019; 187(3): 1028-1045. doi:10.1007/s12010-018-2858-4.
8. Umetani N, Giuliano AE, Hiramatsu SH, Amersi F, Nakagawa T, Martino S, Hoon DS, Prediction of breast tumor progression by integrity of free circulating DNA in serum. J Clin Oncol. 2006; 24(26): 4270–6,
9. Iqbal, Raina V, et al, Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer. SpringerPlus. 2015; 4,
10. Arko-Boham B, et al, Circulating cell-free DNA integrity as a diagnostic and prognostic marker for breast and prostate cancers. Cancer Genetics. 2019: 235-236.
11. Nair MG et al, Estimation of ALU Repetitive Elements in Plasma as a Cost-Effective Liquid Biopsy Tool for Disease Prognosis in Breast Cancer. Cancers. 2023; 15(4): 1054,
12. Adusei E, et al, Reduced Serum Circulation of Cell-Free DNA Following Chemotherapy in Breast Cancer Patients. Medical sciences. 2021; 9(2): 37,
13. Elhelaly R, et al, Circulating Cell Free DNA and DNA Integrity Index as Discriminating Tools between Breast Cancer and Benign Breast Disease. Asian Pac J Cancer Prev. 2022; 23(2): 545-552,