Endocrine

, Volume 60, Issue 2, pp 246–254 | Cite as

Verification of candidate microRNA markers for parathyroid carcinoma

Endocrine Genetics/Epigenetics

Abstract

Purpose

Parathyroid carcinoma (PCa) is a rare endocrine malignancy with poor prognosis and is often difficult to accurately diagnose both before and after surgery. Dysregulated microRNA (miRNA) levels have been identified in PCa using a limited number of samples. The aim of the present study was to verify a group of miRNA markers in a new series of samples to explore their potential significance in PCa diagnosis.

Methods

A total of 58 tissue samples, including 17 PCa lesions and 41 sporadic parathyroid adenomas (PAds), were obtained from 56 primary hyperparathyroidism (pHPT) patients. Candidate miRNAs (miR-139-5p, miR-155-5p, miR-222-3p, miR-26b-5p, miR-296-5p, miR-30b-5p, miR-372-3p, miR-503-5p, miR-517c-3p, miR-7-5p, and miR-126-5p) were quantified by TaqMan real-time quantitative PCR assays.

Results

Up-regulated miR-222 (p = 0.041) levels and down-regulated miR-139 (p = 0.003), miR-30b (p < 0.001), miR-517c (p = 0.038), and miR-126* (p = 0.002) levels were found in PCa relative to PAd. Binary logistic regression analysis showed that miR-139 and miR-30b were the best diagnostic markers. The combination of miR-139 and miR-30b yielded an area under the receiver operating characteristic curve of 0.888. Additionally, serum calcium (r s  = −0.518, p < 0.001), intact parathyroid hormone (iPTH) (r s  = −0.495, p < 0.001), and alkaline phosphatase (ALP) (r s  = −0.523, p < 0.001) levels were negatively correlated with miR-30b levels.

Conclusions

miR-139, miR-222, miR-30b, miR-517c, and miR-126* were differentially expressed between PCa and PAd. The combined analysis of miR-139 and miR-30b may be used as a potential diagnostic strategy for distinguishing PCa from PAd.

Keywords

Parathyroid carcinoma MiRNA Markers RT-qPCR 

Notes

Funding

This work was supported by the Peking Union Medical College Innovative Team Development Program and the Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS-I2M) (2017-I2M-1-001).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12020_2018_1551_MOESM1_ESM.pdf (228 kb)
Supplementary Table 1

References

  1. 1.
    C. Marcocci, F. Saponaro, Epidemiology, pathogenesis of primary hyperparathyroidism: current data. Ann. Endocrinol. 76, 113–115 (2015).  https://doi.org/10.1016/j.ando.2015.03.015 CrossRefGoogle Scholar
  2. 2.
    C. Verdelli, S. Corbetta, Epigenetic alterations in parathyroid cancers. Int. J. Mol. Sci. 18, pii: E310 (2017).  https://doi.org/10.3390/ijms18020310 CrossRefGoogle Scholar
  3. 3.
    K.M. Schulte, N. Talat, Diagnosis and management of parathyroid cancer. Nat. Rev. Endocrinol. 8, 612–622 (2012).  https://doi.org/10.1038/nrendo.2012.102 CrossRefPubMedGoogle Scholar
  4. 4.
    A. Agarwal, R. Pradhan, N. Kumari, N. Krishnani, P. Shukla, S.K. Gupta, G. Chand, A. Mishra, G. Agarwal, A.K. Verma, S.K. Mishra, Molecular characteristics of large parathyroid adenomas. World J. Surg. 40, 607–614 (2016).  https://doi.org/10.1007/s00268-015-3380-2 CrossRefPubMedGoogle Scholar
  5. 5.
    G. Di Leva, M. Garofalo, C.M. Croce, MicroRNAs in cancer. Annu. Rev. Pathol. 9, 287–314 (2014).  https://doi.org/10.1146/annurev-pathol-012513-104715 CrossRefPubMedGoogle Scholar
  6. 6.
    B. Smith, P. Agarwal, N.A. Bhowmick, MicroRNA applications for prostate, ovarian and breast cancer in the era of precision medicine. Endocr. Relat. Cancer 24, R157–R172 (2017).  https://doi.org/10.1530/ERC-16-0525 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    V. Shilo, I.Z. Ben-Dov, M. Nechama, J. Silver, T. Naveh-Many, Parathyroid-specific deletion of dicer-dependent microRNAs abrogates the response of the parathyroid to acute and chronic hypocalcemia and uremia. FASEB J. 29, 3964–3976 (2015).  https://doi.org/10.1096/fj.15-274191 CrossRefPubMedGoogle Scholar
  8. 8.
    V. Vaira, C. Verdelli, I. Forno, S. Corbetta, MicroRNAs in parathyroid physiopathology. Mol. Cell. Endocrinol. 456, 9–15 (2017).  https://doi.org/10.1016/j.mce.2016.10.035 CrossRefPubMedGoogle Scholar
  9. 9.
    S. Corbetta, V. Vaira, V. Guarnieri, A. Scillitani, C. Eller-Vainicher, S. Ferrero, L. Vicentini, I. Chiodini, M. Bisceglia, P. Beck-Peccoz, S. Bosari, A. Spada, Differential expression of microRNAs in human parathyroid carcinomas compared with normal parathyroid tissue. Endocr. Relat. Cancer 17, 135–146 (2010).  https://doi.org/10.1677/ERC-09-0134 CrossRefPubMedGoogle Scholar
  10. 10.
    R. Rahbari, A.K. Holloway, M. He, E. Khanafshar, O.H. Clark, E. Kebebew, Identification of differentially expressed microRNA in parathyroid tumors. Ann. Surg. Oncol. 18, 1158–1165 (2011).  https://doi.org/10.1245/s10434-010-1359-7 CrossRefPubMedGoogle Scholar
  11. 11.
    V. Vaira, F. Elli, I. Forno, V. Guarnieri, C. Verdelli, S. Ferrero, A. Scillitani, L. Vicentini, F. Cetani, G. Mantovani, A. Spada, S. Bosari, S. Corbetta, The microRNA cluster C19MC is deregulated in parathyroid tumours. J. Mol. Endocrinol. 49, 115–124 (2012).  https://doi.org/10.1530/JME-11-0189 CrossRefPubMedGoogle Scholar
  12. 12.
    G. Westin, Molecular genetics and epigenetics of nonfamilial (sporadic) parathyroid tumours. J. Intern. Med. 280, 551–558 (2016).  https://doi.org/10.1111/joim.12458 CrossRefPubMedGoogle Scholar
  13. 13.
    M.I. Rather, M.N. Nagashri, S.S. Swamy, K.S. Gopinath, A. Kumar, Oncogenic microRNA-155 down-regulates tumor suppressor CDC73 and promotes oral squamous cell carcinoma cell proliferation: implications for cancer therapeutics. J. Biol. Chem. 288, 608–618 (2013).  https://doi.org/10.1074/jbc.M112.425736 CrossRefPubMedGoogle Scholar
  14. 14.
    Z.J. Zhao, J. Shen, Circular RNA participates in the carcinogenesis and the malignant behavior of cancer. RNA Biol. 14, 514–521 (2017).  https://doi.org/10.1080/15476286.2015.1122162 CrossRefPubMedGoogle Scholar
  15. 15.
    R.V. Lloyd, R.Y. Osamura, G. Klöppel, J. Rosai, WHO/IARC Classification of Tumours (4th edn., Volume 10) WHO Classification of Tumours of Endocrine Organs. IARC, Lyon (2017)Google Scholar
  16. 16.
    T.D. Schmittgen, K.J. Livak, Analyzing real-time PCR data by the comparative C(t) method. Nat. Protoc. 3, 1101–1108 (2008).  https://doi.org/10.1038/nprot.2008.73 CrossRefPubMedGoogle Scholar
  17. 17.
    D.W. Hosmer, N.L. Hjort, Goodness-of-fit processes for logistic regression: simulation results. Stat. Med. 21, 2723–2738 (2002).  https://doi.org/10.1002/sim.1200 CrossRefPubMedGoogle Scholar
  18. 18.
    J.M. Sharretts, E. Kebebew, W.F. Simonds, Parathyroid cancer. Semin. Oncol. 37, 580–590 (2010).  https://doi.org/10.1053/j.seminoncol.2010.10.013 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    C. Verdelli, I. Forno, V. Vaira, S. Corbetta, MicroRNA deregulation in parathyroid tumours suggests an embryonic signature. J. Endocrinol. Invest. 38, 383–388 (2015).  https://doi.org/10.1007/s40618-014-0234-y CrossRefPubMedGoogle Scholar
  20. 20.
    O. Wang, C. Wang, M. Nie, Q. Cui, H. Guan, Y. Jiang, M. Li, W. Xia, X. Meng, X. Xing, Novel HRPT2/CDC73 gene mutations and loss of expression of parafibromin in Chinese patients with clinically sporadic parathyroid carcinomas. PLoS ONE 7, e45567 (2012).  https://doi.org/10.1371/journal.pone.0045567 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    J.D. Carpten, C.M. Robbins, A. Villablanca, L. Forsberg, S. Presciuttini, J. Bailey-Wilson, W.F. Simonds, E.M. Gillanders, A.M. Kennedy, J.D. Chen, S.K. Agarwal, R. Sood, M.P. Jones, T.Y. Moses, C. Haven, D. Petillo, P.D. Leotlela, B. Harding, D. Cameron, A.A. Pannett, A. Höög, H. Heath, L.A. James-Newton, B. Robinson, R.J. Zarbo, B.M. Cavaco, W. Wassif, N.D. Perrier, I.B. Rosen, U. Kristoffersson, P.D. Turnpenny, L.O. Farnebo, G.M. Besser, C.E. Jackson, H. Morreau, J.M. Trent, R.V. Thakker, S.J. Marx, B.T. Teh, C. Larsson, HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat. Genet. 32, 676–680 (2002).  https://doi.org/10.1038/ng1048 CrossRefPubMedGoogle Scholar
  22. 22.
    F. Cetani, E. Pardi, C. Marcocci, Update on parathyroid carcinoma. J. Endocrinol. Invest. 39, 595–606 (2016).  https://doi.org/10.1007/s40618-016-0447-3 CrossRefPubMedGoogle Scholar
  23. 23.
    C. Pandya, A.V. Uzilov, J. Bellizzi, C.Y. Lau, A.S. Moe, M. Strahl, W. Hamou, L.C. Newman, M.Y. Fink, Y. Antipin, W. Yu, M. Stevenson, B.M. Cavaco, B.T. Teh, R.V. Thakker, H. Morreau, E.E. Schadt, R. Sebra, S.D. Li, A. Arnold, R. Chen, Genomic profiling reveals mutational landscape in parathyroid carcinomas. JCI Insight 2, e92061 (2017).  https://doi.org/10.1172/jci.insight.92061 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    F. Cetani, C. Banti, E. Pardi, S. Borsari, P. Viacava, P. Miccoli, L. Torregrossa, F. Basolo, M.R. Pelizzo, M. Rugge, G. Pennelli, G. Gasparri, M. Papotti, M. Volante, E. Vignali, F. Saponaro, C. Marcocci, CDC73 mutational status and loss of parafibromin in the outcome of parathyroid cancer. Endocr. Connect. 2, 186–195 (2013).  https://doi.org/10.1530/EC-13-0046 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    M. Bacci, E. Giannoni, A. Fearns, R. Ribas, Q. Gao, M.L. Taddei, G. Pintus, M. Dowsett, C.M. Isacke, L.A. Martin, P. Chiarugi, A. Morandi, miR-155 drives metabolic reprogramming of ER+ breast cancer cells following long-term estrogen deprivation and predicts clinical response to aromatase inhibitors. Cancer Res. 76, 1615–1626 (2016).  https://doi.org/10.1158/0008-5472.CAN-15-2038 CrossRefPubMedGoogle Scholar
  26. 26.
    C. Chen, F. Luo, X. Liu, L. Lu, H. Xu, Q. Yang, J. Xue, L. Shi, J. Li, A. Zhang, Q. Liu, NF-kB-regulated exosomal miR-155 promotes the inflammation associated with arsenite carcinogenesis. Cancer Lett. 388, 21–33 (2017).  https://doi.org/10.1016/j.canlet.2016.11.027 CrossRefPubMedGoogle Scholar
  27. 27.
    X. Fu, H. Wen, L. Jing, Y. Yang, W. Wang, X. Liang, K. Nan, Y. Yao, T. Tian, MicroRNA-155-5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway. Cancer Sci. 108, 620–631 (2017).  https://doi.org/10.1111/cas.13177 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    X.F. Zhang, R. Tu, K. Li, P. Ye, X. Cui, Tumor suppressor PTPRJ is a target of miR-155 in colorectal cancer. J. Cell. Biochem. 118, 3391–3400 (2017).  https://doi.org/10.1002/jcb.25995 CrossRefPubMedGoogle Scholar
  29. 29.
    D.N. Gu, Q. Huang, L. Tian, The molecular mechanisms and therapeutic potential of microRNA-7 in cancer. Expert Opin. Ther. Targets 19, 415–426 (2015).  https://doi.org/10.1517/14728222.2014.988708 CrossRefPubMedGoogle Scholar
  30. 30.
    A.R. Glover, J.T. Zhao, A.J. Gill, J. Weiss, N. Mugridge, E. Kim, A.L. Feeney, J.C. Ip, G. Reid, S. Clarke, P.S. Soon, B.G. Robinson, H. Brahmbhatt, J.A. MacDiarmid, S.B. Sidhu, MicroRNA-7 as a tumor suppressor and novel therapeutic for adrenocortical carcinoma. Oncotarget 6, 36675–36688 (2015).  https://doi.org/10.18632/oncotarget.5383 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    J.L. Horsham, C. Ganda, F.C. Kalinowski, R.A. Brown, M.R. Epis, P.J. Leedman, MicroRNA-7: a miRNA with expanding roles in development and disease. Int. J. Biochem. Cell Biol. 69, 215–224 (2015).  https://doi.org/10.1016/j.biocel.2015.11.001 CrossRefPubMedGoogle Scholar
  32. 32.
    T.B. Hansen, J. Kjems, C.K. Damgaard, Circular RNA and miR-7 in cancer. Cancer Res. 73, 5609–5612 (2013).  https://doi.org/10.1158/0008-5472.CAN-13-1568 CrossRefPubMedGoogle Scholar
  33. 33.
    A.M. Silva-Figueroa, N.D. Perrier, Epigenetic processes in sporadic parathyroid neoplasms. Mol. Cell. Endocrinol. (2017).  https://doi.org/10.1016/j.mce.2017.04.007
  34. 34.
    W. Liu, H. Li, Y. Wang, X. Zhao, Y. Guo, J. Jin, R. Chi, MiR-30b-5p functions as a tumor suppressor in cell proliferation, metastasis and epithelial-to-mesenchymal transition by targeting G-protein subunit alpha-13 in renal cell carcinoma. Gene 626, 275–281 (2017).  https://doi.org/10.1016/j.gene.2017.05.040 CrossRefPubMedGoogle Scholar
  35. 35.
    X. Qin, J. Chen, L. Wu, Z. Liu, MiR-30b-5p acts as a tumor suppressor, repressing cell proliferation and cell cycle in human hepatocellular carcinoma. Biomed. Pharmacother. 89, 742–750 (2017).  https://doi.org/10.1016/j.biopha.2017.02.062 CrossRefPubMedGoogle Scholar
  36. 36.
    L. Qin, H.Y. Deng, S.J. Chen, W. Wei, Y.T. Zhang, miR-139 acts as a tumor suppressor in T-cell acute lymphoblastic leukemia by targeting CX chemokine receptor 4. Am. J. Transl. Res. 9, 4059–4070 (2017)PubMedPubMedCentralGoogle Scholar
  37. 37.
    K. Wang, J. Jin, T. Ma, H. Zhai, MiR-139-5p inhibits the tumorigenesis and progression of oral squamous carcinoma cells by targeting HOXA9. J. Cell. Mol. Med. 21, 3730–3740 (2017).  https://doi.org/10.1111/jcmm.13282 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    L. Ng, T.M. Wan, J.H. Man, A.K. Chow, D. Iyer, G. Chen, T.C. Yau, O.S. Lo, D.C. Foo, J.T. Poon, W.K. Leung, R.W. Pang, W.L. Law, Identification of serum miR-139-3p as a non-invasive biomarker for colorectal cancer. Oncotarget 8, 27393–27400 (2017).  https://doi.org/10.18632/oncotarget.16171 PubMedPubMedCentralGoogle Scholar
  39. 39.
    H. Dai, D. Gallagher, S. Schmitt, Z.Y. Pessetto, F. Fan, A.K. Godwin, O. Tawfik, Role of miR-139 as a surrogate marker for tumor aggression in breast cancer. Hum. Pathol. 61, 68–77 (2017).  https://doi.org/10.1016/j.humpath.2016.11.001 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of General Surgery, Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina

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