Document Type : Original Article


1 Institute of Health Sciences, Canakkale Onsekiz Mart University, 17100, Canakkale, Turkey

2 Department of Head and Neck Surgery, Faculty of Medicine, Canakkale Onsekiz Mart University, 17100, Canakkale, Turkey

3 Vocational School of Health Services, Canakkale Onsekiz Mart University, 17100, Canakkale, Turkey


It has been aimed to compare the level of cell-free nucleic acids (DNA, RNA, and miRNA) concentrations in laryngeal cancer patients with the control group composed of healthy individuals. It has been utilized 46 patients with laryngeal carcinoma who were previously diagnosed and treated were included and 46 healthy individuals were included as a control group. Peripheral blood samples were obtained from all participants. DNA, RNA, and miRNA were fluorometrically measured. We applied Mann Whitney U test to compare both groups and the adjusted general lineal model to identify associations between nucleic acid concentrations and tumor stages.  Circulating cell-free microRNA and RNA concentrations in the laryngeal cancer patients were significantly different  (p<0.05). Most importantly, tumor stages were the main factor that altered miRNA concentration in circulation. Our findings support that circulating cell-free miRNA and RNA have potential to be associated with laryngeal cancer. Finally, cell-free miRNAs can be used as a tool to predict different stages of laryngeal cancer.

Graphical Abstract

Evaluation of circulating cell-free nucleic acids in plasma as biomarkers of laryngeal cancer


Main Subjects

Selected author of this article by journal

Dr. Ozge Caglar Cil

Canakkale Onsekiz Mart University


Home Page


Open Access

This article is licensed under a CC BY License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit:


Publisher’s Note

CMBR journal remains neutral with regard to jurisdictional claims in published maps and institutional afflictions.


Letters to Editor

Given that CMBR Journal's policy in accepting articles will be strict and will do its best to ensure that in addition to having the highest quality published articles, the published articles should have the least similarity (maximum 15%). Also, all the figures and tables in the article must be original and the copyright permission of images must be prepared by authors. However, some articles may have flaws and have passed the journal filter, which dear authors may find fault with. Therefore, the editor of the journal asks the authors, if they see an error in the published articles of the journal, to email the article information along with the documents to the journal office.

CMBR Journal welcomes letters to the editor ([email protected], [email protected]) for the post-publication discussions and corrections which allows debate post publication on its site, through the Letters to Editor. Critical letters can be sent to the journal editor as soon as the article is online. Following points are to be considering before sending the letters (comments) to the editor.

[1] Letters that include statements of statistics, facts, research, or theories should include appropriate references, although more than three are discouraged.

[2] Letters that are personal attacks on an author rather than thoughtful criticism of the author’s ideas will not be considered for publication.

[3] There is no limit to the number of words in a letter.

[4] Letter writers should include a statement at the beginning of the letter stating that it is being submitted either for publication or not.

[5] Anonymous letters will not be considered.

[6] Letter writers must include Name, Email Address, Affiliation, mobile phone number, and Comments.

[7] Letters will be answered as soon as possible.

  1. Gupta B, Johnson NW, Kumar N (2016) Global epidemiology of head and neck cancers: a continuing challenge. Oncology 91 (1): 13-23. doi:
  2. Falco M, Tammaro C, Takeuchi T, Cossu AM, Scafuro G, Zappavigna S, Itro A, Addeo R, Scrima M, Lombardi A (2022) Overview on molecular biomarkers for laryngeal cancer: looking for new answers to an old problem. Cancers 14 (7): 1716. doi:
  3. Salhab HA, Fares MY, Khachfe HH, Khachfe HM (2019) Epidemiological Study of Lung Cancer Incidence in Lebanon. Medicina 55 (6): 217. doi:
  4. Pera E, Moreno A, Galindo L (1986) Prognostic factors in laryngeal carcinoma: a multifactorial study of 416 cases. Cancer 58 (4): 928-934. doi:;2-J
  5. Mayeux R (2004) Biomarkers: potential uses and limitations. NeuroRx 1: 182-188. doi:
  6. Fernández-Lázaro D, García Hernández JL, García AC, Córdova Martínez A, Mielgo-Ayuso J, Cruz-Hernández JJ (2020) Liquid biopsy as novel tool in precision medicine: Origins, properties, identification and clinical perspective of cancer’s biomarkers. Diagnostics 10 (4): 215. doi:
  7. Sargeant AM, Pandiri AR, Funk K, Nolte T, Keane K (2023) Carcinogenicity Assessment. In: Haschek and Rousseaux's Handbook of Toxicologic Pathology, Volume 2: Safety Assessment Environmental Toxicologic Pathology. Elsevier, pp 125-172. doi:
  8. Mattox AK, Douville C, Wang Y, Popoli M, Ptak J, Silliman N, Dobbyn L, Schaefer J, Lu S, Pearlman AH (2023) The origin of highly elevated cell-free DNA in healthy individuals and patients with pancreatic, colorectal, lung, or ovarian cancer. Cancer discovery 13 (10): 2166-2179. doi:
  9. Cabus L, Lagarde J, Curado J, Lizano E, Perez-Boza J (2022) Current challenges and best practices for cell-free long RNA biomarker discovery. Biomarker research 10 (1): 62. doi:
  10. Ray SK, Mukherjee S (2022) Cell Free DNA as an Evolving Liquid Biopsy Biomarker for Initial Diagnosis and Therapeutic Nursing in Cancer- An Evolving Aspect in Medical Biotechnology. Curr Pharm Biotechnol 23 (1): 112-122. doi:
  11. Zhang L, Liu X, Wang C, Li X, Tian G, Wang W (2023) Cell-Free RNA Sequencing from Biofluid Samples. Methods in molecular biology (Clifton, NJ) 2695: 9-25. doi:
  12. Pallante P, Visone R, Croce CM, Fusco A (2010) Deregulation of microRNA expression in follicular cell-derived human thyroid carcinomas. Endocrine-related cancer 17 (1): F91-F104. doi:
  13. Salajegheh A, Vosgha H, Rahman AM, Amin M, Smith RA, Lam AK-Y (2015) Modulatory role of miR-205 in. Endocrinology 55: 183-196. doi:
  14. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. cell 75 (5): 843-854. doi:
  15. Yates LA, Norbury CJ, Gilbert RJ (2013) The long and short of microRNA. Cell 153 (3): 516-519. doi:
  16. Møller HG, Rasmussen AP, Andersen HH, Johnsen KB, Henriksen M, Duroux M (2013) A systematic review of microRNA in glioblastoma multiforme: micro-modulators in the mesenchymal mode of migration and invasion. Molecular neurobiology 47: 131-144. doi:
  17. Hayes J, Peruzzi PP, Lawler S (2014) MicroRNAs in cancer: biomarkers, functions and therapy. Trends in molecular medicine 20 (8): 460-469. doi:
  18. Wang J, Chen J, Sen S (2016) MicroRNA as biomarkers and diagnostics. Journal of cellular physiology 231 (1): 25-30. doi:
  19. Cirmena G, Dameri M, Ravera F, Fregatti P, Ballestrero A, Zoppoli G (2021) Assessment of circulating nucleic acids in cancer: from current status to future perspectives and potential clinical applications. Cancers 13 (14): 3460. doi:
  20. Brancaccio M, Natale F, Falco G, Angrisano T (2019) Cell-free DNA methylation: the new frontiers of pancreatic cancer biomarkers’ discovery. Genes 11 (1): 14. doi:
  21. Zhong XY, Ladewig A, Schmid S, Wight E, Hahn S, Holzgreve W (2007) Elevated level of cell-free plasma DNA is associated with breast cancer. Archives of gynecology and obstetrics 276: 327-331. doi:
  22. Kamat AA, Bischoff FZ, Dang D, Baldwin M, Han LY, Lin YG, Merritt WM, Landen CN, Lu C, Gershenson DM (2006) Circulating cell-free DNA: a novel biomarker for response to therapy in ovarian carcinoma. Cancer biology & therapy 5 (10): 1369-1374. doi:
  23. Umetani N, Giuliano AE, Hiramatsu SH, Amersi F, Nakagawa T, Martino S, Hoon DS (2006) Prediction of breast tumor progression by integrity of free circulating DNA in serum. Journal of clinical oncology 24 (26): 4270-4276. doi:
  24. Nunes DN, Kowalski LP, Simpson AJ (2001) Circulating tumor‐derived DNA may permit the early diagnosis of head and neck squamous cell carcinomas. International journal of cancer 92 (2): 214-219. doi:;2-C
  25. Gahan PB (2016) Circulating nucleic acids in early diagnosis, prognosis and treatment monitoring, vol 5. Springer. doi:
  26. Wong BC, Chan KA, Chan AT, Leung S-F, Chan LY, Chow KC, Lo YD (2006) Reduced plasma RNA integrity in nasopharyngeal carcinoma patients. Clinical cancer research 12 (8): 2512-2516. doi:
  27. Xuan L, Qu L, Zhou H, Wang P, Yu H, Wu T, Wang X, Li Q, Tian L, Liu M (2016) Circular RNA: a novel biomarker for progressive laryngeal cancer. American journal of translational research 8 (2): 932. doi:
  28. Hussen BM, Hidayat HJ, Salihi A, Sabir DK, Taheri M, Ghafouri-Fard S (2021) MicroRNA: A signature for cancer progression. Biomedicine & Pharmacotherapy 138: 111528. doi:
  29. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proceedings of the National Academy of Sciences 101 (9): 2999-3004. doi:
  30. Naeini MM, Ardekani AM (2009) Noncoding RNAs and cancer. Avicenna journal of medical biotechnology 1 (2): 55-70. doi:
  31. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nature reviews cancer 6 (11): 857-866. doi:
  32. Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G, Wells W, Kauppinen S, Cole CN (2007) Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer research 67 (24): 11612-11620. doi:
  33. Faber C, Kirchner T, Hlubek F (2009) The impact of microRNAs on colorectal cancer. Virchows Archiv 454: 359-367. doi:
  34. Saito K, Inagaki K, Kamimoto T, Ito Y, Sugita T, Nakajo S, Hirasawa A, Iwamaru A, Ishikura T, Hanaoka H (2013) MicroRNA-196a is a putative diagnostic biomarker and therapeutic target for laryngeal cancer. PloS one 8 (8): e71480. doi:
  35. Kokoska MS, Piccirillo JF, Haughey BH (1995) Gender differences in cancer of the larynx. Annals of Otology, Rhinology & Laryngology 104 (6): 419-424. doi:
  36. Meddeb R, Dache ZAA, Thezenas S, Otandault A, Tanos R, Pastor B, Sanchez C, Azzi J, Tousch G, Azan S (2019) Quantifying circulating cell-free DNA in humans. Scientific reports 9 (1): 5220. doi: