MicroRNA-based molecular classification of papillary thyroid carcinoma

Rosignolo,Francesca; Memeo,Lorenzo; Monzani,Fabio; Colarossi,Cristina; Pecce,Valeria; Verrienti,Antonella; Durante,Cosimo; Grani,Giorgio; Lamartina,Livia; Forte,Stefano; Martinetti,Daniela; Giuffrida,Dario; Russo,Diego; Basolo,Fulvio; Filetti,Sebastiano; Sponziello,Marialuisa

doi:10.3892/ijo.2017.3960

MicroRNA-based molecular classification of papillary thyroid carcinoma

Authors:
- Francesca Rosignolo
- Lorenzo Memeo
- Fabio Monzani
- Cristina Colarossi
- Valeria Pecce
- Antonella Verrienti
- Cosimo Durante
- Giorgio Grani
- Livia Lamartina
- Stefano Forte
- Daniela Martinetti
- Dario Giuffrida
- Diego Russo
- Fulvio Basolo
- Sebastiano Filetti
- Marialuisa Sponziello
View Affiliations

Affiliations: Department of Internal Medicine and Medical Specialties, ‘Sapienza’ University of Rome, Rome, Italy, Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, Italy, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, IOM Ricerca, Viagrande, Italy, Department of Health Sciences, University of Catanzaro ‘Magna Graecia’, Catanzaro, Italy, Department of Histopathology, University of Pisa, Pisa, Italy
Published online on: April 7, 2017 https://doi.org/10.3892/ijo.2017.3960
Pages: 1767-1777

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNA (miRNA) expression is dysregulated in many human malignancies, and a growing number of studies are focused on their potential use as tumor biomarkers. To identify a miRNA signature for papillary thyroid carcinomas (PTC), we investigated miRNA expression profiles in two independent cohorts of PTCs, which included major histological subtypes [classical-type (PTC‑CT), follicular-variant (PTC‑FV), and tall-cell variant (PTC‑TCV)] and cases with low or intermediate risk of recurrence. Using TaqMan® Array Human MicroRNA A+B Cards v3.0, we first performed microRNA profiling of normal and neoplastic thyroid tissues from 29 PTC patients. Promising candidates were then investigated in a second, independent cohort of 76 PTCs using Custom TaqMan® Array MicroRNA Cards. We identified a molecular signature of 11 miRNAs that were significantly upregulated (miR‑146b-5p, miR‑146b-3p, miR‑221-3p, miR‑222‑5p, miR‑222‑3p) or downregulated (miR‑1179, miR‑486‑5p, miR‑204-5p, miR‑7-2-3p, miR‑144-5p, miR‑140-3p) in PTC tissues vs. normal thyroid tissue. Upregulation of miR‑146b-5p and miR‑222‑3p was also significantly associated with an increased risk of recurrence. Higher than normal expression of miR‑146b-5p and miR‑146b-3p characterized PTC‑CT and PTC‑TCV but not PTC‑FV, whereas miR‑21-5p was significantly upregulated only in PTC‑TCV. When PTC‑FV were subclassified as encapsulated (PTC‑EFV) or infiltrative (PTC‑IFV), miR‑204-5p was downregulated in all histological subtypes except PTC‑EFV, which displayed expression levels similar to those of normal thyroid tissues. These findings provide new insights into the molecular classification of PTC, showing that different miRNA expression profiles are associated with different histological types of PTC and different risks of recurrence.

View Figures

View References

1	Davies L and Welch HG: Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 140:317–322. 2014. View Article : Google Scholar : PubMed/NCBI
2	Hay ID, Thompson GB, Grant CS, Bergstralh EJ, Dvorak CE, Gorman CA, Maurer MS, McIver B, Mullan BP, Oberg AL, et al: Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940–1999): Temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. World J Surg. 26:879–885. 2002. View Article : Google Scholar : PubMed/NCBI
3	Lam AK-Y, Lo C-Y and Lam KS-L: Papillary carcinoma of thyroid: A 30-yr clinicopathological review of the histological variants. Endocr Pathol. 16:323–330. 2005. View Article : Google Scholar
4	Shi X, Liu R, Basolo F, Giannini R, Shen X, Teng D, Guan H, Shan Z, Teng W, Musholt TJ, et al: Differential clinicopathological risk and prognosis of major papillary thyroid cancer variants. J Clin Endocrinol Metab. 101:264–274. 2016. View Article : Google Scholar :
5	Agrawal N, Akbani R, Aksoy BA, Ally A, Arachchi H, Asa SL, Auman JT, Balasundaram M, Balu S, Baylin SB, et al Cancer Genome Atlas Research Network: Integrated genomic characterization of papillary thyroid carcinoma. Cell. 159:676–690. 2014. View Article : Google Scholar :
6	Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, et al: Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 499:214–218. 2013. View Article : Google Scholar : PubMed/NCBI
7	Elsheikh TM, Asa SL, Chan JKC, DeLellis RA, Heffess CS, LiVolsi VA and Wenig BM: Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol. 130:736–744. 2008. View Article : Google Scholar : PubMed/NCBI
8	Ghossein R and Livolsi VA: Papillary thyroid carcinoma tall cell variant. Thyroid. 18:1179–1181. 2008. View Article : Google Scholar : PubMed/NCBI
9	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
10	Hall JS, Taylor J, Valentine HR, Irlam JJ, Eustace A, Hoskin PJ, Miller CJ and West CM: Enhanced stability of microRNA expression facilitates classification of FFPE tumour samples exhibiting near total mRNA degradation. Br J Cancer. 107:684–694. 2012. View Article : Google Scholar : PubMed/NCBI
11	Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, et al: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 105:10513–10518. 2008. View Article : Google Scholar : PubMed/NCBI
12	Rosignolo F, Sponziello M, Giacomelli L, Russo D, Pecce V, Biffoni M, Bellantone R, Lombardi CP, Lamartina L, Grani G, et al: Identification of thyroid-associated serum microRNA profiles and their potential use in thyroid cancer follow-up. J Endocr Soc. 1:3–13. 2017.
13	Saiselet M, Pita JM, Augenlicht A, Dom G, Tarabichi M, Fimereli D, Dumont JE, Detours V and Maenhaut C: miRNA expression and function in thyroid carcinomas: A comparative and critical analysis and a model for other cancers. Oncotarget. 7:52475–52492. 2016.PubMed/NCBI
14	Swierniak M, Wojcicka A, Czetwertynska M, Stachlewska E, Maciag M, Wiechno W, Gornicka B, Bogdanska M, Koperski L, de la Chapelle A, et al: In-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma. J Clin Endocrinol Metab. 98:E1401–E1409. 2013. View Article : Google Scholar : PubMed/NCBI
15	Huang Y, Liao D, Pan L, Ye R, Li X, Wang S, Ye C and Chen L: Expressions of miRNAs in papillary thyroid carcinoma and their associations with the BRAFV600E mutation. Eur J Endocrinol. 168:675–681. 2013. View Article : Google Scholar : PubMed/NCBI
16	Hu Y, Wang H, Chen E, Xu Z, Chen B and Lu G: Candidate microRNAs as biomarkers of thyroid carcinoma: A systematic review, meta-analysis, and experimental validation. Cancer Med. 5:2602–2614. 2016. View Article : Google Scholar : PubMed/NCBI
17	Aragon Han P, Weng C-H, Khawaja HT, Nagarajan N, Schneider EB, Umbricht CB, Witwer KW and Zeiger MA: MicroRNA expression and association with clinicopathologic features in papillary thyroid cancer: A systematic review. Thyroid. 25:1322–1329. 2015. View Article : Google Scholar : PubMed/NCBI
18	Dettmer M, Perren A, Moch H, Komminoth P, Nikiforov YE and Nikiforova MN: Comprehensive MicroRNA expression profiling identifies novel markers in follicular variant of papillary thyroid carcinoma. Thyroid. 23:1383–1389. 2013. View Article : Google Scholar : PubMed/NCBI
19	Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, et al: 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 26:1–133. 2016. View Article : Google Scholar :
20	Rosignolo F, Maggisano V, Sponziello M, Celano M, Di Gioia CR, D'Agostino M, Giacomelli L, Verrienti A, Dima M, Pecce V, et al: Reduced expression of THRβ in papillary thyroid carcinomas: Relationship with BRAF mutation, aggressiveness and miR expression. J Endocrinol Invest. 38:1283–1289. 2015. View Article : Google Scholar : PubMed/NCBI
21	Sponziello M, Lavarone E, Pegolo E, Di Loreto C, Puppin C, Russo MA, Bruno R, Filetti S, Durante C, Russo D, et al: Molecular differences between human thyroid follicular adenoma and carcinoma revealed by analysis of a murine model of thyroid cancer. Endocrinology. 154:3043–3053. 2013. View Article : Google Scholar : PubMed/NCBI
22	R Development Core Team: R: A language and environment for statistical computing. R Foundation for Statistical Computing; Vienna: URL http://www.R-project.org/.
23	Wright SP: Adjusted P-values for simultaneous inference. Biometrics. 48:1005–1013. 1992. View Article : Google Scholar
24	Pencheva N, Tran H, Buss C, Huh D, Drobnjak M, Busam K and Tavazoie SF: Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell. 151:1068–1082. 2012. View Article : Google Scholar : PubMed/NCBI
25	Dong W, Yao C, Teng X, Chai J, Yang X and Li B: MiR-140–3p suppressed cell growth and invasion by downregulating the expression of ATP8A1 in non-small cell lung cancer. Tumour Biol. 37:2973–2985. 2016. View Article : Google Scholar
26	Liu R, Liu C, Zhang D, Liu B, Chen X, Rycaj K, Jeter C, Calhoun-Davis T, Li Y, Yang T, et al: miR-199a-3p targets stemness-related and mitogenic signaling pathways to suppress the expansion and tumorigenic capabilities of prostate cancer stem cells. Oncotarget. 7:56628–56642. 2016.PubMed/NCBI
27	Kinose Y, Sawada K, Nakamura K, Sawada I, Toda A, Nakatsuka E, Hashimoto K, Mabuchi S, Takahashi K, Kurachi H, et al: The hypoxia-related microRNA miR-199a-3p displays tumor suppressor functions in ovarian carcinoma. Oncotarget. 6:11342–11356. 2015. View Article : Google Scholar : PubMed/NCBI
28	Minna E, Romeo P, De Cecco L, Dugo M, Cassinelli G, Pilotti S, Degl'Innocenti D, Lanzi C, Casalini P, Pierotti MA, et al: miR-199a-3p displays tumor suppressor functions in papillary thyroid carcinoma. Oncotarget. 5:2513–2528. 2014. View Article : Google Scholar : PubMed/NCBI
29	Chou C-K, Chen R-F, Chou F-F, Chang HW, Chen YJ, Lee YF, Yang KD, Cheng JT, Huang CC and Liu RT: miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF (V600E) mutation. Thyroid. 20:489–494. 2010. View Article : Google Scholar : PubMed/NCBI
30	Mardente S, Mari E, Consorti F, Di Gioia C, Negri R, Etna M, Zicari A and Antonaci A: HMGB1 induces the overexpression of miR-222 and miR-221 and increases growth and motility in papillary thyroid cancer cells. Oncol Rep. 28:2285–2289. 2012.PubMed/NCBI
31	Qiu YH, Wei YP, Shen NJ, Wang ZC, Kan T, Yu WL, Yi B and Zhang YJ: miR-204 inhibits epithelial to mesenchymal transition by targeting slug in intrahepatic cholangiocarcinoma cells. Cell Physiol Biochem. 32:1331–1341. 2013. View Article : Google Scholar : PubMed/NCBI
32	Mancikova V, Castelblanco E, Pineiro-Yanez E, Perales-Paton J, de Cubas AA, Inglada-Perez L, Matias-Guiu X, Capel I, Bella M, Lerma E, et al: MicroRNA deep-sequencing reveals master regulators of follicular and papillary thyroid tumors. Mod Pathol. 28:748–757. 2015. View Article : Google Scholar : PubMed/NCBI
33	Saiselet M, Gacquer D, Spinette A, Craciun L, Decaussin-Petrucci M, Andry G, Detours V and Maenhaut C: New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer. BMC Genomics. 16:8282015. View Article : Google Scholar : PubMed/NCBI
34	Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, Barletta JA, Wenig BM, Al Ghuzlan A, Kakudo K, et al: Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: A paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol. 2:1023–1029. 2016. View Article : Google Scholar : PubMed/NCBI
35	Sheu S-Y, Grabellus F, Schwertheim S, Worm K, Broecker-Preuss M and Schmid KW: Differential miRNA expression profiles in variants of papillary thyroid carcinoma and encapsulated follicular thyroid tumours. Br J Cancer. 102:376–382. 2010. View Article : Google Scholar :
36	Borrelli N, Denaro M, Ugolini C, Poma AM, Miccoli M, Vitti P, Miccoli P and Basolo F: miRNA expression profiling of 'noninvasive follicular thyroid neoplasms with papillary-like nuclear features' compared with adenomas and infiltrative follicular variants of papillary thyroid carcinomas. Mod Pathol. 30:39–51. 2017. View Article : Google Scholar