Abstract
Amaç: Beyin metastazlarının (BM) tedavi yöntemi cerrahi rezek siyon ve/veya radyoterapidir. Gamma Knife radyocerrahisi (GKR) tedavisi, sağlıklı beyin dokusuna toksisiteyi önler. Bu nedenle, BM'li seçilmiş hastaların tedavisinde tercih edilen bir modalitedir. Bu çalışmada, GKR ile tedavi edilen BM hastalarında tanı koyma ve tedavi sonucunu öngörmede biyobelirteç olarak cfDNA seviyeleri, eksozom seviyeleri ve miR-208a ekspresyonunun rolünün araştırıl ması amaçlandı.
Gereç ve Yöntemler: Bu çalışmaya GKR uygulanan beyin metastazlı dokuz hasta dahil edildi. Hastalardan farklı zaman aralıklarında (GKR öncesi, GKR sonrası 1. ay ve nüks döneminde) örnekler alındı. Yaş ve cinsiyet açısından eşleştirilmiş sekiz sağlıklı birey kontrol grubu olarak kullanıldı. Hasta ve kontrol grubundan cfDNA, ekso zom, serum miRNA ve serum ekzozomal miRNA izole edildi.
Bulgular: BM hastalarında cfDNA ve eksozom düzeyleri sağlıklı gruba kıyasla daha yüksek bulundu. GKR sonrası cfDNA ve ekso zom düzeyleri azaldığı, ancak nüks döneminde tekrar arttığı tespit edildi. Serum miR-208a ve serum ekzozomal miR-208a ekspresy onu GKR sonrası artmış bulundu. Serum miR-208a ekspresyonu, akciğer kanseri hastalarında sağlıklı kontrollere ve akciğer kanseri olmayan hastalara kıyasla anlamlı derecede daha yüksek olduğu saptandı. Serum ekzozomal miR-208a ekspresyonu ise akciğer kanseri hastalarında sağlıklı kontrollere kıyasla anlamlı derecede yüksek bulundu.
Sonuç: Bulgularımız, cfDNA ve eksozom düzeylerinin BM hastaları için tanısal belirteç olarak kullanılabileceğini göstermektedir.
Keywords
Project Number
BAP-20200209
References
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Abstract
Objective: The treatment modality for brain metastases (BM) is surgical resection or radiotherapy. Gamma Knife radiosurgery (GKR) treatment prevents toxicity to healthy brain tissue; therefore, this modality is preferred for treating selected patients with BM. Our aim in this study was to investigate the role of cfDNA levels, exosome levels, and miR-208a expressions as biomarkers for diag nosis and predicting the outcome in patients with BM treated with GKR.
Material and Methods: We included nine patients with brain metastasis who received GKR in this study. Samples were taken from patients at different time intervals (before GKR, 1 month after GKR, and at recurrence). Eight age- and gender-matched eight controls were used as healthy individuals. cfDNA, exosome, serum miRNA, and serum exosomal miRNA were isolated from the patient and control groups.
Results: The levels of cfDNA and exosomes were higher in BM patients than in the healthy group. Exosome and cfDNA levels decreased after GKR and increased at recurrence. The expression of serum miR-208a and serum exosomal miR-208a was increased after GKR. The expression of serum miR-208a was significantly higher in patients with lung cancer than in healthy controls and non-lung cancer patients. The expression of serum exosomal miR-208a was found to be significantly higher in patients with lung cancer than in healthy controls.
Conclusion: Our results showed that cfDNA and exosome levels might be used as diagnostic markers for BM patients.
Keywords
Ethical Statement
This study was approved by the Ethical Committee of Bezmialem Vakif University (Ethical no: 2020 - 538).
Supporting Institution
Bezmialem Vakif University
Project Number
BAP-20200209
Thanks
The authors thank Bezmialem Vakif University for its infrastructure and support.
References
- Talmadge JE, Fidler IJ. AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res 2010;70(14):5649-69. google scholar
- Fares J, Fares MY, Khachfe HH, Salhab HA, Fares Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct Target Ther 2020;5(1):28. google scholar
- Nathoo N, Chahlavi A, Barnett GH, Toms SA. Pathobiology of brain metastases. J Clin Pathol 2005;58(3):237-42. google scholar
- Hatiboglu MA, Akdur K, Sawaya R. Neurosurgical management of patients with brain metastasis. Neurosurg Rev 2020;43(2):483-95. google scholar
- Fidler IJ. The Biology of Brain Metastasis: Challenges for Therapy. Cancer J 2015;21(4):284-93. google scholar
- Bankole NDA, Melhaoui A, Arkha Y, Semmar A, Bouyakhlef K, Jiddane M, et al. Outcomes of single brain metastasis treated with gamma knife stereotaxic radiosurgery (GKSR). Our experience on 103 cases. IBRO Neurosci Rep 2023;14:138-45. google scholar
- Hatiboglu MA, Tuzgen S, Akdur K, Chang EL. Treatment of high numbers of brain metastases with Gamma Knife radiosurgery: a review. Acta Neurochir (Wien) 2016;158(4):625-34. google scholar
- Siravegna G, Marsoni S, Siena S, Bardelli A. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol 2017;14(9):531-48. google scholar
- Karacam B, Elbasan EB, Khan I, Akdur K, Mahfooz S, Cavusoglu M, et al. Role of cell-free DNA and extracellular vesicles for diagnosis and surveillance in patients with glioma. The Journal of Liquid Biopsy 2024;4. google scholar
- Khan I, Akdur K, Mahfooz S, Elbasan EB, Sakarcan A, Karacam B, et al. Gamma Knife Radiosurgery Modulates micro-RNA Levels in Patients with Brain Metastasis. Curr Radiopharm 2023;16(3):204-13. google scholar
- Cheok SK, Narayan A, Arnal-Estape A, Gettinger S, Goldberg SB, Kluger HM, et al. Tumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF. JCO Precis Oncol 2021;5. google scholar
- Wu J, Liu Z, Huang T, Wang Y, Song MM, Song T, et al. Cerebrospinal fluid circulating tumor DNA depicts profiling of brain metastasis in NSCLC. Mol Oncol 2023;17(5):810-24. google scholar
- Sabedot TS, Malta TM, Snyder J, Nelson K, Wells M, deCarvalho AC, et al. A serumbased DNA methylation assay provides accurate detection of glioma. Neuro Oncol 2021;23(9):1494-508. google scholar
- Wei L, Wu W, Han L, Yu W, Du Y. A quantitative analysis of the potential biomarkers of non-small cell lung cancer by circulating cell-free DNA. Oncol Lett 2018;16(4):4353-60. google scholar
- Bera A, Russ E, Karaian J, Landa A, Radhakrishnan S, Subramanian M, et al. Circulating Cell-free DNA in Serum as a Marker for the Early Detection of Tumor Recurrence in Breast Cancer Patients. Cancer Diagn Progn 2022;2(3):285-92. google scholar
- Conigliaro A, Cicchini C. Exosome-Mediated Signaling in Epithelial to Mesenchymal Transition and Tumor Progression. J Clin Med 2018;8(1). google scholar
- Oliveira FD, Castanho M, Neves V. Exosomes and Brain Metastases: A Review on Their Role and Potential Applications. Int J Mol Sci 2021;22(19). google scholar
- Aili Y, Maimaitiming N, Qin H, Ji W, Fan G, Wang Z, et al. Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application. Front Oncol 2022;12:983878. google scholar
- Graham R, Gazinska P, Zhang B, Khiabany A, Sinha S, Alaguthurai T, et al. Serum-derived extracellular vesicles from breast cancer patients contribute to differential regulation of T-cell-mediated immune-escape mechanisms in breast cancer subtypes. Front Immunol 2023;14:1204224. google scholar
- Meng X, Muller V, Milde-Langosch K, Trillsch F, Pantel K, Schwarzenbach H. Diagnostic and prognostic relevance of circulating exosomal miR-373, miR-200a, miR-200b and miR-200c in patients with epithelial ovarian cancer. Oncotarget 2016;7(13):16923-35. google scholar
- Shi S, Wang L, Wang C, Xu J, Niu Z. Serum-derived exosomes function as tumor antigens in patients with advanced hepatocellular carcinoma. Mol Immunol 2021;134:210-7. google scholar
- Li Z, Yang H, Ye L, Quan R, Chen M. Role of exosomal miRNAs in brain metastasis affected by radiotherapy. Transl Neurosci 2021;12(1):127-37. google scholar
- Catelan S, Olioso D, Santangelo A, Scapoli C, Tamanini A, Pinna G, et al. miRNAs in Serum Exosomes for Differential Diagnosis of Brain Metastases Cancers (Basel) 2022;14(14). google scholar
- Tang Y, Cui Y, Li Z, Jiao Z, Zhang Y, He Y, et al. Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells. J Exp Clin Cancer Res 2016;35:7. google scholar
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences (Other) |
| Journal Section | Research Article |
| Authors | |
| Project Number | BAP-20200209 |
| Publication Date | June 30, 2025 |
| Submission Date | April 14, 2025 |
| Acceptance Date | May 14, 2025 |
| Published in Issue | Year 2025 Volume: 8 Issue: 2 |
