Öz
Amaç: Bu çalışmanın amacı tiroid kanserlerini belirlemede mikroRNA16-5P ve 221-3P düzeylerinin biyobelirteç olarak kullanılabilirliğini araştırmaktır.
Gereç ve Yöntemler: Şüpheli tiroid nodülü nedeniyle tiroid operasyonu yapılan hastalar çalışmaya alındı. Çalışmaya katılmayı kabul eden toplam 142 hastadan operasyon öncesi EDTA’lı tüpe ve biyokimya tüpüne 3-5 cc venöz kanları alındı. Ameliyat sonrası dönemde patoloji sonuçlarına göre patoloji sonucu malign olan 68 hasta ile patoloji sonucu benign olan 74 hasta kontrol grubu olarak gruplandırıldı. Hastalardan alınan serum örneklerinde miRNA-16-5p ve miRNA-221-3p düzeyleri ölçüldü. miRNA düzeylerinin malign ve benign hasta gruplarındaki düzeyleri analiz edildi.
Sonuçlar: Malign hastaların miRNA-16-5p ve miRNA-221-3p düzeyleri benign hastalara göre istastistiksel olarak anlamlı derecede daha düşük saptandı (p<0.001). Yapılan analizde miRNA-221-3p ve miRNA-16-5p değerlerinin tiroid malignitesini öngörmede tanısal değeri olduğu görüldü. miRNA-221-3p için 21.69’luk bir kesme değeri kullanılarak, ROC eğrisi analizi %89.7’lik sensitivite ve %71.4’lik spesifite saptandı (AUC=0.779, p<0.001). miRNA-16-5p için 15.34’luk bir kesme değeri kullanılarak, ROC eğrisi analizi %32.3’lük sensitivite ve %100’lük spesifite saptandı (AUC=0.708, p<0.001).
Sonuç: miRNA-221-3p ve miRNA-16-5p değerlerinin tiroid malignitesini öngörmede tanısal değeri olduğu, potansiyel biyobelirteç olabilecekleri görülmüştür.
Anahtar Kelimeler
Kaynakça
- 1. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1-133.
- 2. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. cell. 2004;116(2):281-97.
- 3. Boufraqech M, Klubo-Gwiezdzinska J, Kebebew E. MicroRNAs in the thyroid. Best Practice & Research Clinical Endocrinology & Metabolism. 2016;30(5):603-19.
- 4. Liang W, Xie Z, Cui W, Guo Y, Xu L, Wu J, et al. Comprehensive gene and microRNA expression profiling reveals a role for miRNAs in the oncogenic roles of SphK1 in papillary thyroid cancer. Journal of cancer research and clinical oncology. 2017;143:601-11.
- 5. Wang Y, Gong W, Yuan Q. Effects of miR-27a upregulation on thyroid cancer cells migration, invasion, and angiogenesis. Genet Mol Res. 2016;15(4):1-10.
- 6. Zhao H, Tang H, Huang Q, Qiu B, Liu X, Fan D, et al. MiR-101 targets USP22 to inhibit the tumorigenesis of papillary thyroid carcinoma. American journal of cancer research. 2016;6(11):2575.
- 7. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences. 2005;102(39):13944-9.
- 8. Nedaeinia R, Manian M, Jazayeri M, Ranjbar M, Salehi R, Sharifi M, et al. Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer. Cancer gene therapy. 2017;24(2):48-56.
- 9. Visone R, Croce CM. MiRNAs and cancer. The American journal of pathology. 2009;174(4):1131-8.
- 10. Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri M, Troncone G, et al. MicroRNA deregulation in human thyroid papillary carcinomas. Endocrine-related cancer. 2006;13(2):497-508.
- 11. Varkonyi-Gasic E, Hellens RP. Quantitative stem-loop RT-PCR for detection of microRNAs. RNAi and Plant Gene Function Analysis: Methods and Protocols. 2011:145-57.
- 12. Suárez B, Solé C, Márquez M, Nanetti F, Lawrie CH. Circulating microRNAs as cancer biomarkers in liquid biopsies. Systems Biology of MicroRNAs in Cancer. 2022:23-73.
- 13. Gu Z, Li Z, Xu R, Zhu X, Hu R, Xue Y, et al. miR-16-5p suppresses progression and invasion of osteosarcoma via targeting at Smad3. Frontiers in Pharmacology. 2020;11:1324.
- 14. Ruan L, Qian X. MiR-16-5p inhibits breast cancer by reducing AKT3 to restrain NF-κB pathway. Bioscience reports. 2019;39(8):BSR20191611.
- 15. Wang Z, Hu S, Li X, Liu Z, Han D, Wang Y, et al. MiR-16-5p suppresses breast cancer proliferation by targeting ANLN. BMC cancer. 2021;21:1-12.
- 16. Feng X, Dong X, Wu D, Zhao H, Xu C, Li H. Long noncoding RNA small nucleolar RNA host gene 12 promotes papillary thyroid carcinoma cell growth and invasion by targeting miR16-5p. 2020.
- 17. Fang Y, Zhang Q, Chen Z, Guo C, Wu J. Clinical significance and immune characteristics analysis of miR-221-3p and its key target genes related to epithelial-mesenchymal transition in breast cancer. Aging (Albany NY). 2024;16(1):322.
- 18. Krebs M, Solimando AG, Kalogirou C, Marquardt A, Frank T, Sokolakis I, et al. miR-221-3p regulates VEGFR2 expression in high-risk prostate cancer and represents an escape mechanism from sunitinib in vitro. Journal of Clinical Medicine. 2020;9(3):670.
- 19. Rogucki M, Sidorkiewicz I, Niemira M, Dzięcioł JB, Buczyńska A, Adamska A, et al. Expression profile and diagnostic significance of MicroRNAs in papillary thyroid cancer. Cancers. 2022;14(11):2679.
- 20. Diao Y, Fu H, Wang Q. MiR-221 exacerbate cell proliferation and invasion by targeting TIMP3 in papillary thyroid carcinoma. American Journal of Therapeutics. 2017;24(3):e317-e28.
- 21. Ye T, Zhong L, Ye X, Liu J, Li L, Yi H. miR-221-3p and miR-222-3p regulate the SOCS3/STAT3 signaling pathway to downregulate the expression of NIS and reduce radiosensitivity in thyroid cancer. Experimental and Therapeutic Medicine. 2021;21(6):652.
- 22. Rosignolo F, Sponziello M, Giacomelli L, Russo D, Pecce V, Biffoni M, et al. Identification of thyroid-associated serum microRNA profiles and their potential use in thyroid cancer follow-up. Journal of the Endocrine Society. 2017;1(1):3-13.
- 23. Zhang Y, Xu D, Pan J, Yang Z, Chen M, Han J, et al. Dynamic monitoring of circulating microRNAs as a predictive biomarker for the diagnosis and recurrence of papillary thyroid carcinoma. Oncology letters. 2017;13(6):4252-66.
- 24. Verrienti A, Pecce V, Grani G, Del Gatto V, Barp S, Maranghi M, et al. Serum microRNA-146a-5p and microRNA-221-3p as potential clinical biomarkers for papillary thyroid carcinoma. Journal of Endocrinological Investigation. 2024:1-13.
Öz
Objective: The aim of this study is to investigate the usability of microRNA16-5P and 221-3P levels as biomarkers in determining thyroid cancers.
Material and Methods: Patients who underwent thyroid surgery due to suspicious thyroid nodules were included in the study. A total of 142 patients who agreed to participate in the study had 3-5 cc venous blood taken into EDTA tubes and biochemistry tubes before the operation. In the postoperative period, 68 patients with malignant pathology results and 74 patients with benign pathology results were grouped as the control group. miRNA16-5p and miRNA221-3p levels were measured in serum samples taken from the patients. The levels of miRNA levels in malignant and benign patient groups were analyzed.
Results: The miRNA 16-5p and miRNA221-3p levels of malignant patients were statistically significantly lower than those of benign patients (p<0.001). The analysis showed that miRNA-221-3p and miRNA-16-5p values had diagnostic value in predicting thyroid malignancy. Using a cut-off value of 21.69 for miRNA-221-3p, ROC curve analysis detected 89.7% sensitivity and 71.4% specificity (AUC=0.779, p<0.001). Using a cut-off value of 15.34 for miRNA-16-5p, ROC curve analysis detected 32.3% sensitivity and 100% specificity (AUC=0.708, p<0.001).
Conclusion: It was observed that miRNA-221-3p and miRNA-16-5p values had diagnostic value in predicting thyroid malignancy and could be potential biomarkers.
Anahtar Kelimeler
Etik Beyan
Prior to the study, approval was obtained from the Adnan Menderes University Faculty of Medicine Clinical Research Ethics Committee (Date of Approval: 10.10.2019 Protocol No: 2019/120).
Destekleyen Kurum
There is no organization supporting the study.
Kaynakça
- 1. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1-133.
- 2. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. cell. 2004;116(2):281-97.
- 3. Boufraqech M, Klubo-Gwiezdzinska J, Kebebew E. MicroRNAs in the thyroid. Best Practice & Research Clinical Endocrinology & Metabolism. 2016;30(5):603-19.
- 4. Liang W, Xie Z, Cui W, Guo Y, Xu L, Wu J, et al. Comprehensive gene and microRNA expression profiling reveals a role for miRNAs in the oncogenic roles of SphK1 in papillary thyroid cancer. Journal of cancer research and clinical oncology. 2017;143:601-11.
- 5. Wang Y, Gong W, Yuan Q. Effects of miR-27a upregulation on thyroid cancer cells migration, invasion, and angiogenesis. Genet Mol Res. 2016;15(4):1-10.
- 6. Zhao H, Tang H, Huang Q, Qiu B, Liu X, Fan D, et al. MiR-101 targets USP22 to inhibit the tumorigenesis of papillary thyroid carcinoma. American journal of cancer research. 2016;6(11):2575.
- 7. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences. 2005;102(39):13944-9.
- 8. Nedaeinia R, Manian M, Jazayeri M, Ranjbar M, Salehi R, Sharifi M, et al. Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer. Cancer gene therapy. 2017;24(2):48-56.
- 9. Visone R, Croce CM. MiRNAs and cancer. The American journal of pathology. 2009;174(4):1131-8.
- 10. Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri M, Troncone G, et al. MicroRNA deregulation in human thyroid papillary carcinomas. Endocrine-related cancer. 2006;13(2):497-508.
- 11. Varkonyi-Gasic E, Hellens RP. Quantitative stem-loop RT-PCR for detection of microRNAs. RNAi and Plant Gene Function Analysis: Methods and Protocols. 2011:145-57.
- 12. Suárez B, Solé C, Márquez M, Nanetti F, Lawrie CH. Circulating microRNAs as cancer biomarkers in liquid biopsies. Systems Biology of MicroRNAs in Cancer. 2022:23-73.
- 13. Gu Z, Li Z, Xu R, Zhu X, Hu R, Xue Y, et al. miR-16-5p suppresses progression and invasion of osteosarcoma via targeting at Smad3. Frontiers in Pharmacology. 2020;11:1324.
- 14. Ruan L, Qian X. MiR-16-5p inhibits breast cancer by reducing AKT3 to restrain NF-κB pathway. Bioscience reports. 2019;39(8):BSR20191611.
- 15. Wang Z, Hu S, Li X, Liu Z, Han D, Wang Y, et al. MiR-16-5p suppresses breast cancer proliferation by targeting ANLN. BMC cancer. 2021;21:1-12.
- 16. Feng X, Dong X, Wu D, Zhao H, Xu C, Li H. Long noncoding RNA small nucleolar RNA host gene 12 promotes papillary thyroid carcinoma cell growth and invasion by targeting miR16-5p. 2020.
- 17. Fang Y, Zhang Q, Chen Z, Guo C, Wu J. Clinical significance and immune characteristics analysis of miR-221-3p and its key target genes related to epithelial-mesenchymal transition in breast cancer. Aging (Albany NY). 2024;16(1):322.
- 18. Krebs M, Solimando AG, Kalogirou C, Marquardt A, Frank T, Sokolakis I, et al. miR-221-3p regulates VEGFR2 expression in high-risk prostate cancer and represents an escape mechanism from sunitinib in vitro. Journal of Clinical Medicine. 2020;9(3):670.
- 19. Rogucki M, Sidorkiewicz I, Niemira M, Dzięcioł JB, Buczyńska A, Adamska A, et al. Expression profile and diagnostic significance of MicroRNAs in papillary thyroid cancer. Cancers. 2022;14(11):2679.
- 20. Diao Y, Fu H, Wang Q. MiR-221 exacerbate cell proliferation and invasion by targeting TIMP3 in papillary thyroid carcinoma. American Journal of Therapeutics. 2017;24(3):e317-e28.
- 21. Ye T, Zhong L, Ye X, Liu J, Li L, Yi H. miR-221-3p and miR-222-3p regulate the SOCS3/STAT3 signaling pathway to downregulate the expression of NIS and reduce radiosensitivity in thyroid cancer. Experimental and Therapeutic Medicine. 2021;21(6):652.
- 22. Rosignolo F, Sponziello M, Giacomelli L, Russo D, Pecce V, Biffoni M, et al. Identification of thyroid-associated serum microRNA profiles and their potential use in thyroid cancer follow-up. Journal of the Endocrine Society. 2017;1(1):3-13.
- 23. Zhang Y, Xu D, Pan J, Yang Z, Chen M, Han J, et al. Dynamic monitoring of circulating microRNAs as a predictive biomarker for the diagnosis and recurrence of papillary thyroid carcinoma. Oncology letters. 2017;13(6):4252-66.
- 24. Verrienti A, Pecce V, Grani G, Del Gatto V, Barp S, Maranghi M, et al. Serum microRNA-146a-5p and microRNA-221-3p as potential clinical biomarkers for papillary thyroid carcinoma. Journal of Endocrinological Investigation. 2024:1-13.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Onkoloji |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Erken Görünüm Tarihi | 22 Haziran 2025 |
| Yayımlanma Tarihi | 23 Haziran 2025 |
| Gönderilme Tarihi | 18 Nisan 2025 |
| Kabul Tarihi | 17 Haziran 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 26 Sayı: 2 |
