Genomics & Informatics

Korea Genome Organization (한국유전체학회)
권호 표지
DOI QR코드

DOI QR Code

Cell-Free miR-27a, a Potential Diagnostic and Prognostic Biomarker for Gastric Cancer

  • Park, Jong-Lyul (Epigenome Research Center, Genome Institute, KRIBB) ;
  • Kim, Mirang (Epigenome Research Center, Genome Institute, KRIBB) ;
  • Song, Kyu-Sang (Department of Pathology, Chungnam National University College of Medicine) ;
  • Kim, Seon-Young (Epigenome Research Center, Genome Institute, KRIBB) ;
  • Kim, Yong Sung (Epigenome Research Center, Genome Institute, KRIBB)
  • Received : 2015.06.23
  • Accepted : 2015.09.02
  • Published : 2015.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

MicroRNAs (miRNAs) have been demonstrated to play an important role in carcinogenesis. Previous studies revealed that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. In this study, we measured the plasma expression levels of three miRNAs (miR-21, miR-27a, and miR-155) to investigate the usefulness of miRNAs for gastric cancer detection. We initially examined plasma miRNA expression levels in a screening cohort consisting of 15 patients with gastric cancer and 15 healthy controls from Korean population, using TaqMan quantitative real-time polymerase chain reaction. We observed that the expression level of miR-27a was significantly higher in patients with gastric cancer than in healthy controls, whereas the miR-21 and miR-155a expression levels were not significantly higher in the patients with gastric cancer. Therefore, we further validated the miR-27a expression level in 73 paired gastric cancer tissues and in a validation plasma cohort from 35 patients with gastric cancer and 35 healthy controls. In both the gastric cancer tissues and the validation plasma cohort, the miR-27a expression levels were significantly higher in patients with gastric cancer. Receiver-operator characteristic (ROC) analysis of the validation cohort, revealed an area under the ROC curve value of 0.70 with 75% sensitivity and 56% specificity in discriminating gastric cancer. Thus, the miR-27a expression level in plasma could be a useful biomarker for the diagnosis and/or prognosis of gastric cancer.

Keywords

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108. https://doi.org/10.3322/canjclin.55.2.74
  2. Rifai N, Gillette MA, Carr SA. Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol 2006;24:971-983. https://doi.org/10.1038/nbt1235
  3. Kim VN. Small RNAs: classification, biogenesis, and function. Mol Cells 2005;19:1-15. https://doi.org/10.1016/j.molcel.2005.05.026
  4. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281-297. https://doi.org/10.1016/S0092-8674(04)00045-5
  5. Bushati N, Cohen SM. MicroRNA functions. Annu Rev Cell Dev Biol 2007;23:175-205. https://doi.org/10.1146/annurev.cellbio.23.090506.123406
  6. Iorio MV, Croce CM. MicroRNAs in cancer: small molecules with a huge impact. J Clin Oncol 2009;27:5848-5856. https://doi.org/10.1200/JCO.2009.24.0317
  7. Meola N, Gennarino VA, Banfi S. MicroRNAs and genetic diseases. Pathogenetics 2009;2:7. https://doi.org/10.1186/1755-8417-2-7
  8. Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated microRNAs impair TGFbetadependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 2008;13:272-286. https://doi.org/10.1016/j.ccr.2008.02.013
  9. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007;133:647-658. https://doi.org/10.1053/j.gastro.2007.05.022
  10. Jiang S, Zhang HW, Lu MH, He XH, Li Y, Gu H, et al. MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res 2010;70:3119-3127. https://doi.org/10.1158/0008-5472.CAN-09-4250
  11. Lee KH, Chen YL, Yeh SD, Hsiao M, Lin JT, Goan YG, et al. MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation. Oncogene 2009;28:3360- 3370. https://doi.org/10.1038/onc.2009.192
  12. Mishra PJ, Song B, Mishra PJ, Wang Y, Humeniuk R, Banerjee D, et al. miR-24 tumor suppressor activity is regulated independent of p53 and through a target site polymorphism. PLoS One 2009;4:e8445. https://doi.org/10.1371/journal.pone.0008445
  13. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 2006;103:2257-2261. https://doi.org/10.1073/pnas.0510565103
  14. Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 2007; 282:14328-14336. https://doi.org/10.1074/jbc.M611393200
  15. Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, et al. Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci U S A 2008;105:7004-7009. https://doi.org/10.1073/pnas.0801615105
  16. Liu T, Tang H, Lang Y, Liu M, Li X. MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin. Cancer Lett 2009;273:233-242. https://doi.org/10.1016/j.canlet.2008.08.003
  17. Sun Q, Gu H, Zeng Y, Xia Y, Wang Y, Jing Y, et al. Hsa-mir-27a genetic variant contributes to gastric cancer susceptibility through affecting miR-27a and target gene expression. Cancer Sci 2010;101:2241-2247. https://doi.org/10.1111/j.1349-7006.2010.01667.x
  18. Nikolic Z, Savic Pavicevic D, Vucic N, Cidilko S, Filipovic N, Cerovic S, et al. Assessment of association between genetic variants in microRNA genes hsa-miR-499, hsa-miR-196a2 and hsa-miR-27a and prostate cancer risk in Serbian population. Exp Mol Pathol 2015;99:145-150. https://doi.org/10.1016/j.yexmp.2015.06.009
  19. Shi D, Li P, Ma L, Zhong D, Chu H, Yan F, et al. A genetic variant in pre-miR-27a is associated with a reduced renal cell cancer risk in a Chinese population. PLoS One 2012;7:e46566. https://doi.org/10.1371/journal.pone.0046566
  20. Gironella M, Seux M, Xie MJ, Cano C, Tomasini R, Gommeaux J, et al. Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci U S A 2007;104: 16170-16175. https://doi.org/10.1073/pnas.0703942104
  21. Kong W, He L, Coppola M, Guo J, Esposito NN, Coppola D, et al. MicroRNA-155 regulates cell survival, growth, and chemosensitivity by targeting FOXO3a in breast cancer. J Biol Chem 2010;285:17869-17879. https://doi.org/10.1074/jbc.M110.101055
  22. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008;105:10513-10518. https://doi.org/10.1073/pnas.0804549105
  23. El-Hefnawy T, Raja S, Kelly L, Bigbee WL, Kirkwood JM, Luketich JD, et al. Characterization of amplifiable, circulating RNA in plasma and its potential as a tool for cancer diagnostics. Clin Chem 2004;50:564-573. https://doi.org/10.1373/clinchem.2003.028506
  24. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008;18: 997-1006. https://doi.org/10.1038/cr.2008.282
  25. Chim SS, Shing TK, Hung EC, Leung TY, Lau TK, Chiu RW, et al. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem 2008;54:482-490. https://doi.org/10.1373/clinchem.2007.097972
  26. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, et al. Serum microRNAs are promising novel biomarkers. PLoS One 2008;3:e3148. https://doi.org/10.1371/journal.pone.0003148
  27. Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, et al. Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer 2010;102:1174-1179. https://doi.org/10.1038/sj.bjc.6605608
  28. Liu CJ, Kao SY, Tu HF, Tsai MM, Chang KW, Lin SC. Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer. Oral Dis 2010;16:360-364. https://doi.org/10.1111/j.1601-0825.2009.01646.x
  29. Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X. Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer 2010;127:118-126. https://doi.org/10.1002/ijc.25007
  30. Yamamoto Y, Kosaka N, Tanaka M, Koizumi F, Kanai Y, Mizutani T, et al. MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma. Biomarkers 2009;14: 529-538. https://doi.org/10.3109/13547500903150771
  31. Wang Y, Lee CG. MicroRNA and cancer: focus on apoptosis. J Cell Mol Med 2009;13:12-23.
  32. Ferracin M, Lupini L, Salamon I, Saccenti E, Zanzi MV, Rocchi A, et al. Absolute quantification of cell-free microRNAs in cancer patients. Oncotarget 2015;6:14545-14555. https://doi.org/10.18632/oncotarget.3859
  33. Du M, Shi D, Yuan L, Li P, Chu H, Qin C, et al. Circulating miR-497 and miR-663b in plasma are potential novel biomarkers for bladder cancer. Sci Rep 2015;5:10437. https://doi.org/10.1038/srep10437
  34. Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res 2011;39:7223-7233. https://doi.org/10.1093/nar/gkr254
  35. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 2011;13:423-433. https://doi.org/10.1038/ncb2210
  36. Liu R, Zhang C, Hu Z, Li G, Wang C, Yang C, et al. A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer 2011;47:784-791. https://doi.org/10.1016/j.ejca.2010.10.025
  37. Ma Y, Yu S, Zhao W, Lu Z, Chen J. miR-27a regulates the growth, colony formation and migration of pancreatic cancer cells by targeting Sprouty2. Cancer Lett 2010;298:150-158. https://doi.org/10.1016/j.canlet.2010.06.012
  38. Lerner M, Lundgren J, Akhoondi S, Jahn A, Ng HF, Akbari Moqadam F, et al. MiRNA-27a controls FBW7/hCDC4-dependent cyclin E degradation and cell cycle progression. Cell Cycle 2011;10:2172-2183. https://doi.org/10.4161/cc.10.13.16248

Cited by

  1. Protective mechanisms of microRNA-27a against oxygen-glucose deprivation-induced injuries in hippocampal neurons vol.11, pp.8, 2016, https://doi.org/10.4103/1673-5374.189194
  2. Differential expression of miRNAs in the seminal plasma and serum of testicular cancer patients vol.57, pp.3, 2017, https://doi.org/10.1007/s12020-016-1150-z
  3. The Diverse Roles of microRNAs at the Host–Virus Interface vol.10, pp.8, 2018, https://doi.org/10.3390/v10080440
  4. MicroRNAs as non-invasive diagnostic biomarkers for gastric cancer: Current insights and future perspectives vol.24, pp.30, 2018, https://doi.org/10.3748/wjg.v24.i30.3313