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Identification of Differentially Expressed MicroRNA in Parathyroid Tumors

  • Translational Research and Biomarkers
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Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The molecular factors that control parathyroid tumorigenesis are poorly understood. In the absence of local invasion or metastasis, distinguishing benign from malignant parathyroid neoplasm is difficult on histologic examination. We studied the microRNA (miRNA) profile in normal, hyperplastic, and benign and malignant parathyroid tumors to better understand the molecular factors that may play a role in parathyroid tumorigenesis and that may serve as diagnostic markers for parathyroid carcinoma.

Methods

miRNA arrays containing 825 human microRNAs with four duplicate probes per miRNA were used to profile parathyroid tumor (12 adenomas, 9 carcinomas, and 15 hyperplastic) samples normalized to four reference normal parathyroid glands. Differentially expressed miRNA were validated by real-time quantitative TaqMan polymerase chain reaction (PCR).

Results

One hundred fifty-six miRNAs in parathyroid hyperplasia, 277 microRNAs in parathyroid adenoma, and 167 microRNAs in parathyroid carcinomas were significantly dysregulated as compared with normal parathyroid glands [false discovery rate (FDR) < 0.05]. By supervised clustering analysis, all parathyroid carcinomas clustered together. Three miRNAs (miR-26b, miR-30b, and miR-126*) were significantly dysregulated between parathyroid carcinoma and parathyroid adenoma. Receiver-operating characteristic curve analysis showed mir-126* was the best diagnostic marker, with area under the curve of 0.776.

Conclusions

Most miRNAs are downregulated in parathyroid carcinoma, while in parathyroid hyperplasia most miRNAs are upregulated. miRNA profiling shows distinct differentially expressed miRNAs by tumor type which may serve as helpful adjunct to distinguish parathyroid adenoma from carcinoma.

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References

  1. Kebebew E, Clark OH. Parathyroid adenoma, hyperplasia, and carcinoma: localization, technical details of primary neck exploration, and treatment of hypercalcemic crisis. Surg Oncol Clin North Am. 1998;7(4):721–48.

    CAS  Google Scholar 

  2. Carpten JD, Robbins CM, Villablanca A, et al. HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet. 2002;32(4):676–80.

    Google Scholar 

  3. Fernandez-Ranvier GG, Khanafshar E, Tacha D, et al. Defining a molecular phenotype for benign and malignant parathyroid tumors. Cancer. 2009;115(2):334–44.

    Article  PubMed  Google Scholar 

  4. Haven CJ, Howell VM, Eilers PH, et al. Gene expression of parathyroid tumors: molecular subclassification and identification of the potential malignant phenotype. Cancer Res. 2004;64(20):7405–11.

    Article  PubMed  CAS  Google Scholar 

  5. Fujimoto Y, Obara T. How to recognize and treat parathyroid carcinoma. Surg Clin North Am. 1987;67(2):343–57.

    PubMed  CAS  Google Scholar 

  6. Schantz A, Castleman B. Parathyroid carcinoma. A study of 70 cases. Cancer. 1973;31(3):600–5.

    Article  PubMed  CAS  Google Scholar 

  7. Shattuck TM, Valimaki S, Obara T, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 2003;349(18):1722–9.

    Article  PubMed  CAS  Google Scholar 

  8. Mallya SM, Arnold A. Cyclin D1 in parathyroid disease. Front Biosci. 2000;5:D367–71.

    Article  PubMed  CAS  Google Scholar 

  9. Yano S, Sugimoto T, Tsukamoto T, et al. Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas. Eur J Endocrinol. 2003;148(4):403–11.

    Article  PubMed  CAS  Google Scholar 

  10. Iorio MV, Croce CM. MicroRNAs in cancer: small molecules with a huge impact. J Clin Oncol. 2009;27(34):5848–56.

    Article  PubMed  CAS  Google Scholar 

  11. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.

    Article  PubMed  CAS  Google Scholar 

  12. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.

    Article  PubMed  CAS  Google Scholar 

  13. Lagana A, Forte S, Giudice A, et al. miRo: a miRNA knowledge base. Database (Oxford). 2009; 2009:bap008.

  14. Smyth GK, Speed T. Normalization of cDNA microarray data. Methods. 2003;31(4):265–73.

    Article  PubMed  CAS  Google Scholar 

  15. Yang YH, Dudoit S, Luu P, et al. Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res. 2002;30(4):e15.

    Article  PubMed  Google Scholar 

  16. Smyth G. limma: linear models for microarray data. In: Gentleman R, Irizarry RA, Dudoit S, editors. Bioinformatics and computational biology solutions using R and Bioconductor. New York: Springer; 2005. p 397–420.

    Chapter  Google Scholar 

  17. Smyth GK. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004; 3:Article3.

    Google Scholar 

  18. Lee PK, Jarosek SL, Virnig BA, et al. Trends in the incidence and treatment of parathyroid cancer in the United States. Cancer. 2007;109(9):1736–41.

    Article  PubMed  Google Scholar 

  19. Kebebew E, Arici C, Duh QY, Clark OH. Localization and reoperation results for persistent and recurrent parathyroid carcinoma. Arch Surg. 2001;136(8):878–85.

    Article  PubMed  CAS  Google Scholar 

  20. Howell VM, Gill A, Clarkson A, et al. Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. J Clin Endocrinol Metab. 2009;94(2):434–41.

    Google Scholar 

  21. Cetani F, Ambrogini E, Viacava P, et al. Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma? Eur J Endocrinol. 2007;156(5):547–54.

    Article  PubMed  CAS  Google Scholar 

  22. Corbetta S, Vaira V, Guarnieri V, et al. Differential expression of microRNAs in human parathyroid carcinomas compared with normal parathyroid tissue. Endocr Relat Cancer. 2010;17(1):135–46.

    Article  PubMed  CAS  Google Scholar 

  23. Kytola S, Farnebo F, Obara T, et al. Patterns of chromosomal imbalances in parathyroid carcinomas. Am J Pathol. 2000;157(2):579–86.

    Article  PubMed  CAS  Google Scholar 

  24. Lu Y, Ryan SL, Elliott DJ, et al. Amplification and overexpression of Hsa-miR-30b, Hsa-miR-30d and KHDRBS3 at 8q24.22-q24.23 in medulloblastoma. PLoS One. 2009;4(7):e6159.

    Google Scholar 

  25. 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(7):615–23.

    Article  PubMed  CAS  Google Scholar 

  26. Jardin F, Callanan M, Penther D, et al. Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4 + CD56 + haematodermic neoplasms and contribute to the aggressiveness of the disease. Leukemia. 2009;23(4):698–707.

    Article  PubMed  CAS  Google Scholar 

  27. Zanette DL, Rivadavia F, Molfetta GA, et al. miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia. Braz J Med Biol Res. 2007;40(11):1435–40.

    Article  PubMed  CAS  Google Scholar 

  28. Ji J, Shi J, Budhu A, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009;361(15):1437–47.

    Article  PubMed  CAS  Google Scholar 

  29. Liu X, Chen Z, Yu J, et al. MicroRNA Profiling and head and neck cancer. Comp Funct Genomics. 2009:837514.

  30. Liu B, Peng XC, Zheng XL, et al. MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer. 2009;66(2):169–75.

    Article  PubMed  Google Scholar 

  31. Sun Y, Bai Y, Zhang F, et al. miR-126 inhibits non-small cell lung cancer cells proliferation by targeting EGFL7. Biochem Biophys Res Commun. 2010;391(3):1483–9.

    Article  PubMed  CAS  Google Scholar 

  32. Guo C, Sah JF, Beard L, et al. The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Genes Chromosomes Cancer. 2008;47(11):939–46.

    Article  PubMed  CAS  Google Scholar 

  33. Hussein K, Dralle W, Theophile K, et al. Megakaryocytic expression of miRNA 10a, 17-5p, 20a and 126 in Philadelphia chromosome-negative myeloproliferative neoplasm. Ann Hematol. 2009;88(4):325–32.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported in part by grants from the UCSF Comprehensive Cancer Center, American Cancer Society, and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

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Correspondence to Electron Kebebew MD.

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Rahbari, R., Holloway, A.K., He, M. et al. Identification of Differentially Expressed MicroRNA in Parathyroid Tumors. Ann Surg Oncol 18, 1158–1165 (2011). https://doi.org/10.1245/s10434-010-1359-7

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  • DOI: https://doi.org/10.1245/s10434-010-1359-7

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