Potency of Various MicroRNA as Sputum Biomarker in Lung Cancer

Ahmad Razi Maulana Alnaz, Aqyl Hanif Abdillah, Rasyid Ridha


Introduction: Lung cancer is one the deadliest cancer known. Current method using low-dose CT scan to screen lung cancer applied are proved to reduce mortality, but lack in accuracy leading to overdiagnosis. Current researches are mostly seeking for a non-invasive and cost-effective method, hence biomarkers such as microRNA has a potency to screen and diagnose lung cancer. This literature review aimed to discuss the potency of microRNA in sputum as a biomarker in screening lung cancer.

Methods: The study is conducted by literature searching for related journals in search engines such as PubMed, Science Direct, and Google Scholar with keywords. 35 articles were included with relevance and within 10 years publication.

Result: MicroRNA is a short non-coding RNA which regulates gene expression. It acts in an oncogene or tumor suppressor gene regulation. DNA mutations or defects occurred in cancer particularly in lung cancer causes increase or decrease of microRNA expression. Alterations of microRNA expression in sputum detected by rt-PCR may represent progressions of lung cancer from a cell cycle dysregulation and provides better sensitivity and specificity among other biomarkers. Combinations of miRNA species offer increase of  sensitivity and specificity. Particular types of microRNA are able to classify the types of lung cancer in progress.

Conclusion: MicroRNA has the promising potency and strong accuracy with a non-invasive and cost-effective procedure in detecting early signs of lung cancer occurrence and can be further applied as biomarker used in lung cancer.

Keywords: Biomarker; Lung Cancer; microRNA; Screening; Sputum


Biomarker; Lung Cancer; microRNA; Screening; Sputum

Full Text:



Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. 2. American Cancer Society. Global Cancer Facts & Figures. 4th ed. Atlanta: American Cancer Society; 2018. 3. Shoshan-Barmatz V, Bishitz Y, Paul A, Krelin Y, Nakdimon I, Peled N, et al. A molecular signature of lung cancer: Potential biomarkers for adenocarcinoma and squamous cell carcinoma. Oncotarget. 2017;8(62):105492–509. 4. Barta JA, Powell CA, Wisnivesky JP. Global epidemiology of lung cancer. Ann Glob Heal. 2019;85(1):1–16. 5. Hirsch FR, Scagliotti G V., Mulshine JL, Kwon R, Curran WJ, Wu YL, et al. Lung cancer: current therapies and new targeted treatments. Lancet [Internet]. 2017;389(10066):299–311. Available from: http://dx.doi.org/10.1016/S0140-6736(16)30958-8 6. Sears CR, Mazzone PJ. Biomarkers in Lung Cancer. Clin Chest Med [Internet]. 2020;41(1):115–27. Available from: https://doi.org/10.1016/j.ccm.2019.10.004 7. Azar FE, Azami-Aghdash S, Pournaghi-Azar F, Mazdaki A, Rezapour A, Ebrahimi P, et al. Cost-effectiveness of lung cancer screening and treatment methods: A systematic review of systematic reviews. BMC Health Serv Res. 2017;17(1):1–9. 8. Hubers AJ, Prinsen CFM, Sozzi G, Witte BI, Thunnissen E. Molecular sputum analysis for the diagnosis of lung cancer. Br J Cancer [Internet]. 2013;109(3):530–7. Available from: http://dx.doi.org/10.1038/bjc.2013.393 9. Seijo LM, Peled N, Ajona D, Boeri M, Field JK, Sozzi G, et al. Biomarkers in Lung Cancer Screening: Achievements, Promises, and Challenges. J Thorac Oncol [Internet]. 2019;14(3):343–57. Available from: https://doi.org/10.1016/j.jtho.2018.11.023 10. Gustafson D, Tyryshkin K, Renwick N. microRNA-guided diagnostics in clinical samples. Best Pract Res Clin Endocrinol Metab [Internet]. 2016;30(5):563–75. Available from: http://dx.doi.org/10.1016/j.beem.2016.07.002 11. Lampignano R, Kloten V, Krahn T, Schlange T. Integrating circulating miRNA analysis in the clinical management of lung cancer: Present or future? Mol Aspects Med [Internet]. 2020;72(January):100844. Available from: https://doi.org/10.1016/j.mam.2020.100844 12. Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018;141(4):1202–7. 13. Ghafouri-Fard S, Shoorei H, Branicki W, Taheri M. Non-coding RNA profile in lung cancer. Exp Mol Pathol [Internet]. 2020;114:104411. Available from: https://doi.org/10.1016/j.yexmp.2020.104411 14. Travis WD. Lung Cancer Pathology: Current Concepts. Clin Chest Med [Internet]. 2020;41(1):67–85. Available from: https://doi.org/10.1016/j.ccm.2019.11.001 15. Wu KL, Tsai YM, Lien CT, Kuo PL, Hung JY. The roles of microRNA in lung cancer. Int J Mol Sci. 2019;20(7):1–25. 16. Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis. 2015;35(1):3–11. 17. Gulyaeva LF, Kushlinskiy NE. Regulatory mechanisms of microRNA expression. J Transl Med. 2016 Dec 20;14(1):143. 18. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell [Internet]. 2011;144(5):646–74. Available from: http://dx.doi.org/10.1016/j.cell.2011.02.013 19. Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther. 2016;(November 2015). 20. Xing L, Su J, Guarnera MA, Zhang H, Cai L, Zhou R, et al. Sputum microRNA biomarkers for identifying lung cancer in indeterminate solitary pulmonary nodules. Clin Cancer Res. 2015;21(2):484–9. 21. Anjuman N, Li N, Guarnera M, Stass SA, Jiang F. Evaluation of lung flute in sputum samples for molecular analysis of lung cancer. Clin Transl Med. 2013;2(1):15. 22. Razzak R, Bédard ELR, Kim JO, Gazala S, Guo L, Ghosh S, et al. MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small-cell lung cancer: A prospective case-control study. Curr Oncol. 2016;23(2):e86–94. 23. Xie Y, Todd NW, Liu Z, Zhan M, Fang H Bin, Peng H, et al. Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer. Lung Cancer. 2010 Feb;67(2):170–6. 24. Li N, Ma J, Guarnera MA, Fang H, Cai L, Jiang F. Digital PCR quantification of miRNAs in sputum for diagnosis of lung cancer. J Cancer Res Clin Oncol. 2014;140(1):145–50. 25. Xing L, Todd NW, Yu L, Fang H, Jiang F. Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers. Mod Pathol. 2010;23(8):1157–64. 26. A. B, H.R.K. K, S.J. M, H.A. M, A. M, M. Y, et al. Altered miR-223 expression in sputum for diagnosis of non-small cell lung cancer. Avicenna J Med Biotechnol. 2017;9(4):189–95. 27. Shen J, Liao J, Guarnera MA, Fang H Bin, Cai L, Stass SA, et al. Analysis of microRNAs in sputum to improve computed tomography for lung cancer diagnosis. J Thorac Oncol [Internet]. 2014;9(1):33–40. Available from: http://dx.doi.org/10.1097/JTO.0000000000000025 28. Kim CE, Tchou-Wong KM, Rom WN. Sputum-based molecular biomarkers for the early detection of lung cancer: Limitations and promise. Cancers (Basel). 2011;3(3):2975–89. 29. Su Y, Fang H Bin, Jiang F. Integrating DNA methylation and microRNA biomarkers in sputum for lung cancer detection. Clin Epigenetics [Internet]. 2016;8(1):1–9. Available from: http://dx.doi.org/10.1186/s13148-016-0275-5 30. Inamura K, Ishikawa Y. MicroRNA In Lung Cancer: Novel Biomarkers and Potential Tools for Treatment. J Clin Med. 2016;5(3):36. 31. Su J, Anjuman N, Guarnera MA, Zhang H, Stass SA, Jiang F. Analysis of Lung Flute-collected Sputum for Lung Cancer Diagnosis. Biomark Insights. 2015;10:55–61. 32. Gyoba J, Shan S, Roa W, Bédard ELR. Diagnosing Lung Cancers through Examination of Micro-RNA Biomarkers in Blood , Plasma , Serum and Sputum : A Review and Summary of Current Literature. 2016;(Lcc):1–14. 33. Rivard C, Rozeboom L, Feser W, Baron A, Miller Y, Bunn P, et al. miRNA for Early Detection of Lung Cancer: Comparison of Tissue, Sputum and Plasma Signatures. J Thorac Oncol. 2017;12(8):S1540. 34. Lu S, Kong H, Hou Y, Ge D, Huang W, Ou J, et al. Two plasma microRNA panels for diagnosis and subtype discrimination of lung cancer. Lung Cancer. 2018;123(November 2017):44–51. 35. Poroyko V, Mirzapoiazova T, Nam A, Mambetsariev I, Mambetsariev B, Wu X, et al. Exosomal miRNAs species in the blood of small cell and nonsmall cell lung cancer patients. Oncotarget. 2018;9(28):19793–806.


  • There are currently no refbacks.