RESUMEN

El mesotelioma pleural maligno es un tumor extremadamente agresivo, difícil de diagnosticar, que se origina en el mesotelio de la membrana pleural y que comúnmente se asocia a la exposición al asbesto. Los síntomas se manifiestan después de 20-40 años de la exposición al carcinógeno, pero posterior al diagnóstico presenta una sobrevivencia de 9-12 meses. La prueba diagnóstica confirmatoria del mesotelioma pleural maligno o «estándar de oro» es la tinción por inmunohistoquímica para marcadores tisulares; pero al no existir un marcador 100% certero del diagnóstico, éste suele ser difícil y complejo. Aunado a lo anterior, el mesotelioma pleural maligno es difícil de distinguir de carcinomas de origen epitelial que invaden la pleura, tal como el adenocarcinoma pulmonar. Los miRNAs son RNAs de doble hebra que regulan los mecanismos celulares esenciales a nivel postranscripcional, son tejido-específico y su expresión no depende de la edad o raza del individuo. Estudios recientes han demostrado que la expresión de los miRNAs es aberrante en diversos tumores y que podría utilizarse como biomarcador de diagnóstico, revelando una herramienta diagnóstica alternativa. La presente revisión se enfoca en los estudios de los miRNAs tisulares como posibles biomarcadores de diagnóstico del mesotelioma pleural maligno, así como en las características biológicas de los miRNAs.

PALABRAS CLAVE

Mesotelioma pleural maligno, diagnóstico, microRNAs.

REFERENCIAS

1. Kaufman AJ, Pass HI. Current concepts in malignant pleural mesothelioma. Expert Rev Anticancer Ther 2008;8:293-303.

2. Bianchi C, Bianchi T. Malignant mesotelioma: global incidence and relationship with asbestos. Ind Health 2007;45:379-387.

3. Roggli VL, Sharma A, Butnor KJ, Sporn T, Vollmer RT. Malignant mesothelioma and occupational exposure to asbestos: a clinicopathological correlation of 1445 cases. Ultrastruct Pathol 2002;26:55-65.

4. Robinson BW, Lake RA. Advances in malignant mesothelioma. N Engl J Med 2005;353:1591-1603.

5. Ray M, Kindler HL. Malignant pleural mesothelioma an update on biomarkers and treatment. Chest 2009;136:888-896.

6. Delgermaa V, Takahashi K, Park EK, Le GV, Hara T, Sorahan T. Global mesothelioma deaths reported to the World Health Organization between 1994 and 2008. Bull World Health Organ 2011;89:716-724.

7. Park EK, Takahashi K, Hoshuyama T, et al. Global magnitude of reported and unreported mesothelioma. Environ Health Perspect 2011;119:514-518.

8. Aguilar-Madrid G, Robles-Pérez E, Juárez-Pérez CA, Alvarado-Caballero I, Rico-Méndez FG, Javier KG. Case-control study of pleural mesothelioma in workers with social security in Mexico. Am J Ind Med 2010;53:241-251.

9. Addis B, Roche H. Problems in mesothelioma diagnosis. Histopathology 2009;54:55-68.

10. Husain AN, Colby TV, Ordóñez NG, et al. Guidelines for pathologic diagnosis of malignant mesothelioma: a consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med 2009;133:1317-1331.

11. Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell 2009;136:642-655.

12. Ortiz-Quintero B. RNA interferente: from origins to a novel tool for gene silencing. Rev Invest Clin 2009;61:412-427.

13. Calin GA, Croce CM. MicroRNA-cancer connection: the beginning of a new tale. Cancer Res 2006;66:7390-7394.

14. Schetter AJ, Leung SY, Sohn JJ. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 2008; 299: 425-436.

15. Yanaihara N, Caplen N, Bowman E, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006;9:189-198.

16. Patnaik SK, Kannisto E, Knudsen S, Yendamuri S. Evaluation of microRNA expression profiles that may predict recurrence of localized stage I non-small cell lung cancer after surgical resection. Cancer Res 2010;70:36-45.

17. Zhou X, Marian C, Makambi KH. MicroRNA-9 as potential biomarker for breast cancer local recurrence and tumor estrogen receptor status. PloS One 2012;7:e39011.

18. Dedes KJ, Natrajan R, Lambros MB. Down-regulation of the miRNA master regulators Drosha ad Dicer is associated with specific subgroups of breast cancer. Eur J Cancer 2011;47:138-150.

19. Bloomston M, Frankel WL, Petrocca F, et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA 2007;297:1901-1908.

20. Wu H, Zhu S, Mo YY. Suppression of cell growth and invasion by miR-205 in breast cancer. Cell Res 2009;19:439-448.

21. Asangani IA, Rasheed SA, Nikolova DA, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 2008;27:2128-2136.

22. Zhang X, Liu S, Hu T, Liu S, He Y, Sun S. Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology 2009;50:490-499.

23. Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000;403:901-906.

24. Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 2003;113:25-36.

25. Sato M, Shames DS, Gazdar AF, Minna JD. A translational view of the molecular pathogenesis of lung cancer. J Thorac Oncol 2007;2:327-343.

26. Salk JJ, Horwitz MS. Passenger mutations as a marker of clonal cell lineages in emerging neoplasia. Semin Cancer Biol 2010;20:294-303.

27. Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 2001;294:858-862.

28. Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J 2002;21:4663-4670.

29. Han J, Lee Y, Yeom KH, et al. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 2006;125:887-901.

30. Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 2004;10:185-191.

31. Provost P, Dishart D, Doucet J, Frendewey D, Samuelsson B, Radmark O. Ribonuclease activity and RNA binding of recombinant human Dicer. EMBO J 2002;21:5864-5874.

32. Azuma-Mukai A, Oguri H, Mituyama T, et al. Characterization of endogenous human Argonautes and their miRNA partners in RNA silencing. Proc Natl Acad Sci USA 2008;105:7964-7969.

33. Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci USA 2003;100:9779-9784.

34. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005;120:15-20.

35. Wang B, Yanez A, Novina CD. MicroRNA-repressed mRNAs contain 40S but not 60S components. Proc Natl Acad Sci 2008;105:5343-5348.

36. Giraldez AJ, Mishima Y, Rihel J, et al. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 2006;312:75-79.

37. Balatti V, Maniero S, Ferracin M, et al. MicroRNAs dysregulation in human malignant pleural mesothelioma. J Thorac Oncol 2011;6:844-851.

38. Sara Busacca, Germano S, De Cecco L, et al. MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications. Am J Respir Cell Mol Biol 2010;42:312-319.

39. Gee GV, Koestler DC, Christensen BC, et al. Downregulated microRNAs in the differential diagnosis of malignant pleural mesotelioma. Int J Cancer 2010;127:2859-2869.

40. Benjamin H, Lebanony D, Rosenwald S, et al. A diagnostic assay based on microRNA expression accurately identifies malignant pleural mesothelioma. J Mol Diagn 2010;12:771-779.

41. Santarelli L, Strafella E, Staffolani S, et al. Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma. PLoS One 2011;6:18232.

42. Guled M, Lahti L, Lindholm PM, et al. CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma -A miRNA microarray analysis. Genes Chromosomes Cancer 2009;48:615-623.

43. Pradervand S, Weber J, Lemoine F, et al. Concordance among digital gene expression, microarrays, and qPCR when measuring differential expression of microRNAs. Biotechniques 2010;48:219-222.

44. Sato F, Tsuchiya S, Terasawa K, Tsujimoto G. Intra-platform repeatability and inter-platform comparability of microRNA microarray technology. PLoS One 2009;4:5540.

45. Pepe MS, Etzioni R, Feng Z, et al. Phases of biomarker development for early detection of cancer. J Natl Cancer Inst 2001;93:1054-1061.