Journals / Aydın Sağlık Dergisi / 2026 / Cilt: 6 Sayı: 2

A New Candidate Biomarker in Peripheral Blood of Patients with Metastatic Lung Cancer: High DICER1 Expression Level

Metastatik Akciğer Kanserli Hastaların Periferik Kanında Yeni Aday Biyomarker: Yüksek DICER1 Ekspresyon Düzeyi

Mukaddes Avşar Saral(İSTANBUL ÜNİVERSİTESİ)0000-0002-5489-9088
Nurcan Çırak(İSTANBUL ÜNİVERSİTESİ)0000-0001-5974-4731
Gözde Türkcan(İSTANBUL ÜNİVERSİTESİ)0000-0003-0964-4817
Demet A. Ödemiş(İSTANBUL ÜNİVERSİTESİ)0000-0002-2271-8481
Şeref Buğra Tunçer(İSTANBUL ÜNİVERSİTESİ)0000-0001-8023-3223
Seda K. Erciyas(İSTANBUL ÜNİVERSİTESİ)0000-0003-4417-4005
Özge Ş. Erdoğan(İSTANBUL ÜNİVERSİTESİ)0000-0002-0893-1251
Makbule Tambaş(İSTANBUL ÜNİVERSİTESİ)0000-0003-2464-0101
Hülya Yazıcı(İSTANBUL ÜNİVERSİTESİ)0000-0002-8919-0482
Pages
123–138
Publication Date
2020-06-01
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

In addition, the study is the first to investigate DICER1 expression in the peripheral blood samples of lung cancer patients.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Objective: Lung cancer is in the first place in the world in terms of cancerrelated incidence and mortality.
📊
Key Findings & Data:DICER1 has an important function in microRNA biogenesis.
💡
Conclusion & Impact:In addition, the study is the first to investigate DICER1 expression in the peripheral blood samples of lung cancer patients.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Akciğer kanseri · DICER1 · Metastaz

Abstract

Objective: Lung cancer is in the first place in the world in terms of cancerrelated incidence and mortality. Since cancer is a multifactorial disease, it is very important to try to illuminate the mechanisms associated with cancer. It is known that miRNA activity, which is closely related to carcinogenesis, is impaired with various mechanisms. One of these mechanisms is the molecular changes that occur during miRNA process. DICER1 has an important function in microRNA biogenesis. In our study, it was aimed to investigate the effect of DICER1 gene expression level on metastatic lung cancer development. Material and Method: The study groups consist of peripheral blood samples of 47 patients with metastatic lung cancer who had recently been diagnosed but had never been treated and 45 healthy people. The investigated DICER1 target gene was examined simultaneously with the HPRT1 reference gene by using the Real-Time PCR method. The results of DICER1 gene expression levels of patients and those of healthy individuals were compared. The results were evaluated by using the 2-ΔΔCT method. Results: The expression level of DICER1 gene in the peripheral blood lymphocytes of patients with metastatic lung cancer was increased by 1.756 (2-ΔΔCt) fold compared to the healthy control group and the increased expression level was statistically significant, p <0.05. Discussion and Conclusion: The results of our study were found correlated with the results of the study on tumor tissue of lung cancer in the literature. In this context, it is suggested that DICER1 expression in the peripheral blood lymphocytes will provide information about the level of DICER1 expression in tumor tissue of metastatic lung patients whose tissues cannot be reached. In addition, the study is the first to investigate DICER1 expression in the peripheral blood samples of lung cancer patients.

Özet

Amaç: Akciğer kanseri, dünyada kansere bağlı insidans ve mortalite açısından birinci sırada yer almaktadır. Kanserin multifaktoriyel bir hastalık olması nedeniyle kanserle ilişkili mekanizmaların aydınlatılmaya çalışılması oldukça önem taşımaktadır. Kanserle yakından ilgili olan miRNA aktivitesinin çeşitli mekanizmalarla bozulduğu bilinmektedir. Bu mekanizmalardan biri de miRNA işlenmesi sırasında meydana gelen moleküler değişikliklerdir. DICER1, microRNA biyogenezinde önemli bir yere sahiptir. Çalışmamızda, akciğer kanserli hastaların periferik kan lenfositlerinde DICER1 gen ifade düzeyinin sağlıklı kişilerle karşılaştırılarak metastatik akciğer kanseri gelişimindeki etkisinin araştırılması amaçlanmıştır. Materyal ve Metot: Çalışma grubu yeni tanı almış ve daha önce hiç tedavi görmemiş 47 akciğer kanserli hasta ile 45 sağlıklı kişinin periferik kan örneklerinden oluşturuldu. Araştırılan DICER1 hedef geni, HPRT1 referans geni ile eş zamanlı olarak Gerçek-Zamanlı PCR yöntemiyle incelendi. Akciğer kanser hastalarına ait gen ekspresyon düzeyi ile sağlıklı kişilerden oluşan kontrol grubu DICER1 gen ekspresyon sonuçları karşılaştırıldı. Sonuçlar 2-ΔΔCT metodu kullanılarak değerlendirildi. Sonuçlar: Akciğer kanser hastalarının periferik kan lenfositlerinde DICER1 gen ifade düzeyinin (2-ΔΔCt) kontrol grubuna göre 1,756 kat arttığı, bu artmış ekspresyon düzeyinin istatistiksel açıdan anlamlı (p< 0,05) olduğu görüldü. Tartışma: Metastatik akciğer kanserli hastaların periferik kan lenfositlerinde yapılan çalışmamızdan çıkan sonuçlar literatürde tümör dokusunda yapılan çalışma ile korelasyon göstermektedir. Bu bağlamda periferik kan lenfositlerindeki DICER1 ekspresyon düzeyinin, metastatik akciğer hastalarının tümör dokusundaki DICER1 gen ekspresyon düzeyi hakkında bilgi vereceğini ve dokusuna ulaşılamayan hastalar için iyi bir uygulama olacağını düşündürmektedir. Ayrıca çalışma literatürde akciğer kanserli hastaların periferik kan örneklerinde DICER1 ekspresyonunun araştırıldığı ilk çalışma niteliği taşımaktadır.

🔖

Cite This Article

Saral, M. A., Çırak, N., Türkcan, G., Ödemiş, D. A., Tunçer, Ş. B., Erciyas, S. K., Erdoğan, Ö. Ş., Tambaş, M., Yazıcı, H. (2020). A New Candidate Biomarker in Peripheral Blood of Patients with Metastatic Lung Cancer: High DICER1 Expression Level. Aydın Sağlık Dergisi, Cilt: 6 Sayı: 2, 123–138. https://ajindex.com/articles/1458676

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (39)

  1. Alberg, A. J., Ford, J. G., Samet, J. M., & American College of Chest, P. (2007). Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest, 132(3 Suppl), 29S-55S. doi: 10.1378/chest.07-1347
  2. Bade, B. C., & Dela Cruz, C. S. (2020). Lung Cancer 2020: Epidemiology, Etiology, and Prevention. Clin Chest Med, 41(1), 1-24. doi: 10.1016/j.ccm.2019.10.001
  3. Boeri, M., Pastorino, U., & Sozzi, G. (2012). Role of microRNAs in lung cancer: microRNA signatures in cancer prognosis. Cancer J, 18(3), 268-274. doi: 10.1097/PPO.0b013e318258b743
  4. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 68(6), 394-424. doi: 10.3322/caac.21492
  5. Cagle, P. T., Allen, T. C., & Olsen, R. J. (2013). Lung cancer biomarkers: present status and future developments. Arch Pathol Lab Med, 137(9), 1191-1198. doi: 10.5858/arpa.2013-0319-CR
  6. Chatziandreou, I., Tsioli, P., Sakellariou, S., Mourkioti, I., Giannopoulou, I., Levidou, G.,. Saetta, A. A. (2015). Comprehensive Molecular Analysis of NSCLC; Clinicopathological Associations. PLoS One, 10(7), e0133859. doi: 10.1371/journal.pone.0133859
  7. Chen, X., Li, W. F., Wu, X., Zhang, H. C., Chen, L., Zhang, P. Y.,. Tang, K. F. (2017). Dicer regulates non-homologous end joining and is associated with chemosensitivity in colon cancer patients. Carcinogenesis, 38(9), 873-882. doi: 10.1093/carcin/bgx059
  8. Cheng, L., Alexander, R. E., Maclennan, G. T., Cummings, O. W., Montironi, R., Lopez-Beltran, A.,. Zhang, S. (2012). Molecular pathology of lung cancer: key to personalized medicine. Mod Pathol, 25(3), 347-369. doi: 10.1038/modpathol.2011.215
  9. Chiosea, S., Jelezcova, E., Chandran, U., Acquafondata, M., McHale, T., Sobol, R. W., & Dhir, R. (2006). Up-regulation of dicer, a component of the MicroRNA machinery, in prostate adenocarcinoma. Am J Pathol, 169(5), 1812-1820. doi: 10.2353/ajpath.2006.060480
  10. Chiosea, S., Jelezcova, E., Chandran, U., Luo, J., Mantha, G., Sobol, R. W., & Dacic, S. (2007). Overexpression of Dicer in precursor lesions of lung adenocarcinoma. Cancer Res, 67(5), 2345-2350. doi: 10.1158/0008- 5472.CAN-06-3533
  11. Del Vescovo, V., & Denti, M. A. (2015). microRNA and Lung Cancer. Adv Exp Med Biol, 889, 153-177. doi: 10.1007/978-3-319-23730-5_9
  12. Erson, A. E., & Petty, E. M. (2009). miRNAs and cancer: New research developments and potential clinical applications. Cancer Biol Ther, 8(24), 2317-2322. doi: 10.4161/cbt.8.24.10765
  13. Foulkes, W. D., Priest, J. R., & Duchaine, T. F. (2014). DICER1: mutations, microRNAs and mechanisms. Nat Rev Cancer, 14(10), 662- 672. doi: 10.1038/nrc3802
  14. Gurtner, A., Falcone, E., Garibaldi, F., & Piaggio, G. (2016). Dysregulation of microRNA biogenesis in cancer: the impact of mutant p53 on Drosha complex activity. J Exp Clin Cancer Res, 35, 45. doi: 10.1186/s13046-016-0319-x
  15. Iwakawa, H. O., & Tomari, Y. (2015). The Functions of MicroRNAs: mRNA Decay and Translational Repression. Trends Cell Biol, 25(11), 651-665. doi: 10.1016/j.tcb.2015.07.011
  16. Jakymiw, A., Patel, R. S., Deming, N., Bhattacharyya, I., Shah, P., Lamont, R. J.,. Chan, E. K. (2010). Overexpression of dicer as a result of reduced let-7 MicroRNA levels contributes to increased cell proliferation of oral cancer cells. Genes Chromosomes Cancer, 49(6), 549-559. doi: 10.1002/gcc.20765
  17. Karube, Y., Tanaka, H., Osada, H., Tomida, S., Tatematsu, Y., Yanagisawa, K.,. Takahashi, T. (2005). Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci, 96(2), 111-115. doi: 10.1111/j.1349-7006.2005.00015.x
  18. Lee, S. S., Min, H., Ha, J. Y., Kim, B. H., Choi, M. S., & Kim, S. (2019). Dysregulation of the miRNA biogenesis components DICER1, DROSHA, DGCR8 and AGO2 in clear cell renal cell carcinoma in both a Korean cohort and the cancer genome atlas kidney clear cell carcinoma cohort. Oncol Lett, 18(4), 4337-4345. doi: 10.3892/ol.2019.10759
  19. Macfarlane, L. A., & Murphy, P. R. (2010). MicroRNA: Biogenesis, Function and Role in Cancer. Curr Genomics, 11(7), 537-561. doi: 10.2174/138920210793175895
  20. Malhotra, J., Malvezzi, M., Negri, E., La Vecchia, C., & Boffetta, P. (2016). Risk factors for lung cancer worldwide. Eur Respir J, 48(3), 889- 902. doi: 10.1183/13993003.00359-2016
  21. Pampalakis, G., Diamandis, E. P., Katsaros, D., & Sotiropoulou, G. (2010). Down-regulation of dicer expression in ovarian cancer tissues. Clin Biochem, 43(3), 324-327. doi: 10.1016/j.clinbiochem.2009.09.014
  22. Prodromaki, E., Korpetinou, A., Giannopoulou, E., Vlotinou, E., Chatziathanasiadou, M., Papachristou, N. I.,. Papachristou, D. J.
  23. . Expression of the microRNA regulators Drosha, Dicer and Ago2 in non-small cell lung carcinomas. Cell Oncol (Dordr), 38(4), 307-317. doi: 10.1007/s13402-015-0231-y
  24. Ramalingam, S. S., Owonikoko, T. K., & Khuri, F. R. (2011). Lung cancer: New biological insights and recent therapeutic advances. CA Cancer J Clin, 61(2), 91-112. doi: 10.3322/caac.20102
  25. Rupaimoole, R., & Slack, F. J. (2017). MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov, 16(3), 203-222. doi: 10.1038/nrd.2016.246
  26. To, S. K. Y., Mak, A. S. C., Eva Fung, Y. M., Che, C. M., Li, S. S., Deng, W.,. Wong, A. S. T. (2017). beta-catenin downregulates Dicer to promote ovarian cancer metastasis. Oncogene, 36(43), 5927-5938. doi: 10.1038/onc.2017.185
  27. Torre, L. A., Siegel, R. L., & Jemal, A. (2016). Lung Cancer Statistics. Adv Exp Med Biol, 893, 1-19. doi: 10.1007/978-3-319-24223-1_1
  28. Villalobos, P., & Wistuba, II. (2017). Lung Cancer Biomarkers. Hematol Oncol Clin North Am, 31(1), 13-29. doi: 10.1016/j.hoc.2016.08.006
  29. Wakelee, H. A., Chang, E. T., Gomez, S. L., Keegan, T. H., Feskanich, D., Clarke, C. A.,. West, D. W. (2007). Lung cancer incidence in never smokers. J Clin Oncol, 25(5), 472-478. doi: 10.1200/JCO.2006.07.2983
  30. Zhang, L., Huang, J., Yang, N., Greshock, J., Megraw, M. S., Giannakakis, A.,. Coukos, G. (2006). microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A, 103(24), 9136-9141. doi: 10.1073/pnas.0508889103
  31. Chatziandreou, I., Tsioli, P., Sakellariou, S., Mourkioti, I., Giannopoulou, I., Levidou, G.,. Saetta, A. A. (2015). Comprehensive Molecular Analysis of NSCLC; Clinicopathological Associations. PLoS One, 10(7), e0133859. doi: 10.1371/journal.pone.0133859
  32. Chen, X., Li, W. F., Wu, X., Zhang, H. C., Chen, L., Zhang, P. Y.,. Tang, K. F. (2017). Dicer regulates non-homologous end joining and is associated with chemosensitivity in colon cancer patients. Carcinogenesis, 38(9), 873-882. doi: 10.1093/carcin/bgx059
  33. Cheng, L., Alexander, R. E., Maclennan, G. T., Cummings, O. W., Montironi, R., Lopez-Beltran, A.,. Zhang, S. (2012). Molecular pathology of lung cancer: key to personalized medicine. Mod Pathol, 25(3), 347-369. doi: 10.1038/modpathol.2011.215
  34. Jakymiw, A., Patel, R. S., Deming, N., Bhattacharyya, I., Shah, P., Lamont, R. J.,. Chan, E. K. (2010). Overexpression of dicer as a result of reduced let-7 MicroRNA levels contributes to increased cell proliferation of oral cancer cells. Genes Chromosomes Cancer, 49(6), 549-559. doi: 10.1002/gcc.20765
  35. Karube, Y., Tanaka, H., Osada, H., Tomida, S., Tatematsu, Y., Yanagisawa, K.,. Takahashi, T. (2005). Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci, 96(2), 111-115. doi: 10.1111/j.1349-7006.2005.00015.x
  36. Prodromaki, E., Korpetinou, A., Giannopoulou, E., Vlotinou, E., Chatziathanasiadou, M., Papachristou, N. I.,. Papachristou, D. J.
  37. To, S. K. Y., Mak, A. S. C., Eva Fung, Y. M., Che, C. M., Li, S. S., Deng, W.,. Wong, A. S. T. (2017). beta-catenin downregulates Dicer to promote ovarian cancer metastasis. Oncogene, 36(43), 5927-5938. doi: 10.1038/onc.2017.185
  38. Wakelee, H. A., Chang, E. T., Gomez, S. L., Keegan, T. H., Feskanich, D., Clarke, C. A.,. West, D. W. (2007). Lung cancer incidence in never smokers. J Clin Oncol, 25(5), 472-478. doi: 10.1200/JCO.2006.07.2983
  39. Zhang, L., Huang, J., Yang, N., Greshock, J., Megraw, M. S., Giannakakis, A.,. Coukos, G. (2006). microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A, 103(24), 9136-9141. doi: 10.1073/pnas.0508889103