Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

J Cancer 2024; 15(9):2573-2579. doi:10.7150/jca.93184 This issue Cite

Research Paper

Prognostic significance of BRCA1 and BRCA2 methylation status in circulating cell-free DNA of Pancreatic Cancer patients

Triantafyllia Koukaki1, Ioanna Balgkouranidou1, Eirini Biziota1, Anastasios Karayiannakis2, Helen Bolanaki2, Evangelos Karamitrousis3, Paul Zarogoulidis4✉, Savas Deftereos5, Charalampos Charalampidis6, Aris Ioannidis7, Dimitrios Matthaios8, Kyriakos Amarantidis1, Stylianos Kakolyris1

1. Department of Medical Oncology, Medical School, Democritus University of Thrace, Greece
2. Department of 2nd Surgery, Medical School, Democritus University of Thrace, Greece
3. University Medical Oncology department, Aristotle University of Thessaloniki, Papageorgiou General Hospital.
4. Pulmonary Oncology Department, General Clinic Euromedica, Thessaloniki, Greece
5. Radiology Department, Medical School, Democritus University of Thrace, Greece
6. Pathology Department, University of Cyprus, Cyprus
7. Surgery Department, Genesis Private Clinic, Thessaloniki, Greece
8. Oncology Department, General Hospital of Rhodes, Greece

✉ Corresponding author: Paul Zarogoulidis, M.D., Ph.D., Pulmonary Department, General Clinic Euromedica, Thessaloniki, Greece. Tel.: 00306977271974; E-mail: pzarogcom.

Citation:
Koukaki T, Balgkouranidou I, Biziota E, Karayiannakis A, Bolanaki H, Karamitrousis E, Zarogoulidis P, Deftereos S, Charalampidis C, Ioannidis A, Matthaios D, Amarantidis K, Kakolyris S. Prognostic significance of BRCA1 and BRCA2 methylation status in circulating cell-free DNA of Pancreatic Cancer patients. J Cancer 2024; 15(9):2573-2579. doi:10.7150/jca.93184. https://www.jcancer.org/v15p2573.htm
Other styles

File import instruction

Abstract

Graphic abstract

Introduction: Pancreatic cancer is the most fatal cancer type in the world. Its high mortality is mostly correlated to the absence of symptoms and the difficulty in early diagnosis, which in the majority of the cases occurs when the disease has already spread metastasis. Nowadays, tests that could predict early diagnosis are not available yet and the number of prognostic tests is limited. Hence, there is an urgent need for biomarkers capable of detecting early development or the rapid progression of the disease.

Patients and Methods: DNA methylation represents the most frequent epigenetic event among tumor suppressor genes that are involved in various carcinogenic pathways. In the recent study we have tried to evaluate, for the first time, the prognostic value of BRCA1 and BRCA2 methylation in the cell-free DNA of pancreatic cancer patients. Using methylation-specific real-time PCR we examined the methylation status of BRCA1 and BRCA2 in 55 patients with operable and 50 patients with metastatic pancreatic cancer. In the operable disease setting, BRCA1 was found to be methylated in 33/55 (63.5%) patients examined while BRCA2 was also highly methylated in 31/55 (56.3%). In the metastatic disease, BRCA1 was found to be methylated in 26/50 (52%) while BRCA2 was found methylated in 23/50 (46%).

Results: All control samples were negative for BRCA1 orBRCA2 promoter methylation. Patients with operable pancreatic cancer and a methylated BRCA1 and BRCA2 promoter status had a statistically significant poorer outcome as compared with patients with a non-methylated one (p=0.012 and p=0.001, respectively).

Conclusion: In this study plasma methylation of BRCA1 and BRCA2 represents a frequent event in both the operable as well as in the metastatic setting. BRCA1 and BRCA2 methylation was significant and correlated with decreased survival in patients with operable pancreatic cancer. A larger cohort of patients is required to further explore the potential of these findings as well as to investigate whether BRCA1/2 methylation in plasma could serve as a potential prognostic biomarker in pancreatic cancer.

Keywords: BRCA1, BRCA2gene, DNA methylation, Cell-free DNA, prognosis

Citation styles

APA
Koukaki, T., Balgkouranidou, I., Biziota, E., Karayiannakis, A., Bolanaki, H., Karamitrousis, E., Zarogoulidis, P., Deftereos, S., Charalampidis, C., Ioannidis, A., Matthaios, D., Amarantidis, K., Kakolyris, S. (2024). Prognostic significance of BRCA1 and BRCA2 methylation status in circulating cell-free DNA of Pancreatic Cancer patients. Journal of Cancer, 15(9), 2573-2579. https://doi.org/10.7150/jca.93184.

ACS
Koukaki, T.; Balgkouranidou, I.; Biziota, E.; Karayiannakis, A.; Bolanaki, H.; Karamitrousis, E.; Zarogoulidis, P.; Deftereos, S.; Charalampidis, C.; Ioannidis, A.; Matthaios, D.; Amarantidis, K.; Kakolyris, S. Prognostic significance of BRCA1 and BRCA2 methylation status in circulating cell-free DNA of Pancreatic Cancer patients. J. Cancer 2024, 15 (9), 2573-2579. DOI: 10.7150/jca.93184.

NLM
Koukaki T, Balgkouranidou I, Biziota E, Karayiannakis A, Bolanaki H, Karamitrousis E, Zarogoulidis P, Deftereos S, Charalampidis C, Ioannidis A, Matthaios D, Amarantidis K, Kakolyris S. Prognostic significance of BRCA1 and BRCA2 methylation status in circulating cell-free DNA of Pancreatic Cancer patients. J Cancer 2024; 15(9):2573-2579. doi:10.7150/jca.93184. https://www.jcancer.org/v15p2573.htm

CSE
Koukaki T, Balgkouranidou I, Biziota E, Karayiannakis A, Bolanaki H, Karamitrousis E, Zarogoulidis P, Deftereos S, Charalampidis C, Ioannidis A, Matthaios D, Amarantidis K, Kakolyris S. 2024. Prognostic significance of BRCA1 and BRCA2 methylation status in circulating cell-free DNA of Pancreatic Cancer patients. J Cancer. 15(9):2573-2579.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use