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P. 170
itself. Second, 5 identified “HCC specific” miRNAs to 2005. J Clin Oncol 2009;27:1485-91.
were all down-regulated in tumor tissue, which 4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J
Clin 2015;65:5-29.
requires more sensitive methods of detection for 5. El Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology
future clinical application. It is known that RNA-seq and molecular carcinogenesis. Gastroenterology 2007;132:2557-76.
[61]
has a better sensitivity than RT-qPCR, but the latter 6. Cabibbo G, Maida M, Genco C, Antonucci M, Camma C. Causes of
and prevention strategies for hepatocellular carcinoma. Semin Oncol
is more accurate and usually used for the validation 2012;39:374-83.
of candidate miRNAs. We also observed that the 7. Wogan GN. Aflatoxins as risk factors for hepatocellular carcinoma in
[62]
changes of miRNAs in tumor tissue detected by RT- 8. humans. Cancer Res 1992;52:s2114-8.
Li J, Shi W, Gao Y, Yang B, Jing X, Shan S, Wang Y, Du Z. Analysis
qPCR were minor compared to those by RNA-seq of microRNA expression profiles in human hepatitis B virus-related
[Supplementary Table 3]. Even more challenging 9. hepatocellular carcinoma. Clin Lab 2013;59:1009-15.
Park KU, Seo YS, Lee YH, Park J, Hwang I, Kang KJ, Nam J, Kim
is to measure these miRNAs in circulation in pre- SW, Kim JY. Altered microRNA expression profile in hepatitis B virus-
diagnostic samples, which strongly suggests a dire related hepatocellular carcinoma. Gene 2015;573:278-84.
need for development of more sensitive PCR-based 10. Diaz G, Melis M, Tice A, Kleiner DE, Mishra L, Zamboni F, Farci P.
Identification of microRNAs specifically expressed in hepatitis C virus-
assays that can be used in large population studies. associated hepatocellular carcinoma. Int J Cancer 2013;133:816-24.
11. Edge SB, Compton CC. The American Joint Committee on Cancer: the
In conclusion, our study identified 33 miRNAs 7th edition of the AJCC cancer staging manual and the future of TNM.
Ann Surg Oncol 2010;17:1471-4.
significantly aberrantly expressed in HCC tumors with 12. Chu A, Robertson G, Brooks D, Mungall AJ, Birol I, Coope R, Ma
over 2-fold changes, and for the first time distinguished Y, Jones S, Marra MA. Large-scale profiling of microRNAs for The
Cancer Genome Atlas. Nucleic Acids Res 2016;44:e3.
5 of them as having “HCC tumor type specificity”, 13. Barrett T, Troup DB, Wilhite SE, Ledoux P, Rudnev D, Evangelista
while another 8 are “tumor common” alterations. C, Kim IF, Soboleva A, Tomashevsky M, Marshall KA, Phillippy
We also found several etiology-related miRNA panels, KH, Sherman PM, Muertter RN, Muertter RN. NCBI GEO: archive
but most overlap with those observed in overall HCC. for high-throughput functional genomic data. Nucleic Acids Res
2009;37:D885-90.
These findings have promising applications to better 14. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the
comparative C(T) method. Nat Protoc 2008;3:1101-8.
understand the common mechanisms underline 15. Eminaga S, Christodoulou DC, Vigneault F, Church GM, Seidman
tumorigenesis and improve precision prevention JG. Quantification of microRNA expression with next-generation
and therapy for specific cancers by targeting tumor sequencing. Curr Protoc Mol Biol 2013;Chapter 4:Unit.
specific miRNAs. Large retrospective and prospective 16. Rice J, Roberts H, Burton J, Pan J, States V, Rai SN, Galandiuk S.
Assay reproducibility in clinical studies of plasma miRNA. PLoS One
studies to evaluate miRNA changes in circulation and 2015;10:e0121948.
trends during cancer development are warranted. 17. Tibshirani R, Hastie T, Narasimhan B, Chu G. Diagnosis of multiple
cancer types by shrunken centroids of gene expression. Proc Natl Acad
Sci U S A 2002;99:6567-72.
Acknowledgments 18. Simon R, Lam A, Li MC, Ngan M, Menenzes S, Zhao Y. Analysis
We used public available miRNAs and clinical data of gene expression data using BRB-ArrayTools. Cancer Inform
2007;3:11-7.
from TCGA in this manuscript. Information about 19. Lu TP, Lee CY, Tsai MH, Chiu YC, Hsiao CK, Lai LC, Chuang EY.
TCGA and the investigators and institutions that miRSystem: an integrated system for characterizing enriched functions
constitute the TCGA research network can be found and pathways of microRNA targets. PLoS One 2012;7:e42390.
at http://cancergenome.nih.gov. 20. Chen J, Bardes EE, Aronow BJ, Jegga AG. ToppGene Suite for gene
list enrichment analysis and candidate gene prioritization. Nucleic
Acids Res 2009;37:W305-11.
Financial support and sponsorship 21. Lee L, Wang K, Li G, Xie Z, Wang Y, Xu J, Sun S, Pocalyko D, Bhak
This work is supported by NIH grants R01 ES005116, J, Kim C, Lee KH, Jang YJ, Yeom YI, Yoo HS, Hwang S. Liverome:
P30 ES009089, P30 CA013696, R03 CA156629. The a curated database of liver cancer-related gene signatures with self-
contained context information. BMC Genomics 2011;12 Suppl 3:S3.
Cancer Genome Atlas (TCGA) project is supported by 22. Hou W, Bonkovsky HL. Non-coding RNAs in hepatitis C-induced
the NCI and NHGRI. hepatocellular carcinoma: dysregulation and implications for
early detection, diagnosis and therapy. World J Gastroenterol
2013;19:7836-45.
Conflicts of interest 23. Pogribny IP, Rusyn I. Role of epigenetic aberrations in the development
There are no conflicts of interest. and progression of human hepatocellular carcinoma. Cancer Lett
2014;342:223-30.
24. Salvi A, Abeni E, Portolani N, Barlati S, De Petro G. Human
REFERENCES hepatocellular carcinoma cell-specific miRNAs reveal the differential
expression of miR-24 and miR-27a in cirrhotic/non-cirrhotic HCC. Int
1. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat J Oncol 2013;42:391-402.
Rev Cancer 2006;6:857-66. 25. Li B, Huang P, Qiu J, Liao Y, Hong J, Yuan Y. MicroRNA-130a is
2. Lyra-Gonzalez I, Flores-Fong LE, Gonzalez-Garcia I, Medina- down-regulated in hepatocellular carcinoma and associates with poor
Preciado D, Armendariz-Borunda J. MicroRNAs dysregulation in prognosis. Med Oncol 2014;31:230.
hepatocellular carcinoma: insights in genomic medicine. World J 26. Zhang X, Daucher M, Armistead D, Russell R, Kottilil S. MicroRNA
Hepatol 2015;7:1530-40. expression profiling in HCV-infected human hepatoma cells identifies
3. Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma potential anti-viral targets induced by interferon-alpha. PLoS One
incidence, mortality, and survival trends in the United States from 1975 2013;8:e55733.
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