The combined use of miRNAs and mRNAs as biomarkers for the diagnosis of papillary thyroid carcinoma

Zhao,Yinlong; Liu,Xiaodong; Zhong,Lili; He,Mengzi; Chen,Silin; Wang,Tiejun; Ma,Shumei

doi:10.3892/ijmm.2015.2305

The combined use of miRNAs and mRNAs as biomarkers for the diagnosis of papillary thyroid carcinoma

Authors:
- Yinlong Zhao
- Xiaodong Liu
- Lili Zhong
- Mengzi He
- Silin Chen
- Tiejun Wang
- Shumei Ma
View Affiliations

Affiliations: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: August 5, 2015 https://doi.org/10.3892/ijmm.2015.2305
Pages: 1097-1103

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

Thyroid carcinoma (TC) is the most common malignancy of the endocrine system, and papillary thyroid carcinoma (PTC) accounts for the largest proportion of cases with TC. Although histology is considered the gold standard in the diagnosis of PTC, the sensitivity and specificity of this method is low. Therefore, developing novel diagnostic and prognostic biomarkers for PTC is essential. MicroRNAs (miRNAs or miRs) and their target RNAs play critical roles in tumorigenesis and tumor progression. Thus, the characteristic miRNA and mRNA expression profiles may function as diagnostic biomarkers for tumors, making it possible to predict the tumor stage and the prognosis of patients. In the present study, we detected miRNAs and mRNAs which can function as novel biomarkers for the diagnosis of PTC. The sensitivity of the diagnostic tests was evaluated by receiver operating characteristic curve analysis. Pearson's correlation analysis was used to determine the correlation between mRNAs and miRNAs, and cancer types. We found that the area under the curve (AUC) values of 8 miRNAs (miR-106a, miR-15a, miR-30a, miR-30b, miR-20a, miR-20b, miR-30d and miR-30e) and 8 mRNAs [axis inhibition protein 2 (AXIN2), integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor) (ITGA3), tumor protein p53 inducible nuclear protein (TP53INP)1, TP53INP2, B-cell CLL/lymphoma 2 (BCL2), phosphatase and tensin homolog (PTEN), FOS and K(lysine) acetyltransferase 2B (KAT2B)] were >0.90. The combination of miR-15a and AXIN2 significantly improved the diagnostic accuracy. Therefore, our data indicate that the differential expression of miRNAs combined with that of their target mRNAs may serve as a powerful biomarker for distinguishing PTC from benign tissues.

View Figures

View References

1	Siegel R, Ma J, Zou Z and Jemal A: Cancer Statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Goldfarb M and Casillas J: Unmet information and support needs in newly diagnosed thyroid cancer: comparison of adolescents/young adults (AYA) and older patients. J Cancer Surviv. 8:394–401. 2014. View Article : Google Scholar : PubMed/NCBI
3	Olaleye O, Ekrikpo U, Moorthy R, Lyne O, Wiseberg J, Black M and Mitchell D: Increasing incidence of differentiated thyroid cancer in South East England: 1987–2006. Eur Arch Otorhinolaryngol. 268:899–906. 2011. View Article : Google Scholar
4	Chen AY, Jemal A and Ward EM: Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005. Cancer. 115:3801–3807. 2009. View Article : Google Scholar : PubMed/NCBI
5	Li X, Abdel-Mageed AB, Mondal D and Kandil E: MicroRNA expression profiles in differentiated thyroid cancer, a review. Int J Clin Exp Med. 6:74–80. 2013.
6	Sethi K, Sarkar S, Das S, Mohanty B and Mandal M: Biomarkers for the diagnosis of thyroid cancer. J Exp Ther Oncol. 8:341–352. 2010.
7	Torréns JI and Burch HB: Serum thyroglobulin measurement. Utility in clinical practice. Endocrinol Metab Clin North Am. 30:429–467. 2001. View Article : Google Scholar : PubMed/NCBI
8	Kebebew E and Reiff E: Patients with differentiated thyroid cancer have a venous gradient in thyroglobulin levels. Cancer. 109:1078–1081. 2007. View Article : Google Scholar : PubMed/NCBI
9	Weinberger PM, Adam BL, Gourin CG, Moretz WH III, Bollag RJ, Wang BY, Liu Z, Lee JR and Terris DJ: Association of nuclear, cytoplasmic expression of galectin-3 with beta-catenin/Wnt-pathway activation in thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 133:503–510. 2007. View Article : Google Scholar : PubMed/NCBI
10	Ito Y, Yoshida H, Tomoda C, Miya A, Kobayashi K, Matsuzuka F, Kakudo K, Kuma K and Miyauchi A: HBME-1 expression in follicular tumor of the thyroid: an investigation of whether it can be used as a marker to diagnose follicular carcinoma. Anticancer Res. 25:179–182. 2005.PubMed/NCBI
11	Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 9:189–198. 2006. View Article : Google Scholar : PubMed/NCBI
12	Sassen S, Miska EA and Caldas C: MicroRNA: implications for cancer. Virchows Archiv. 452:1–10. 2008. View Article : Google Scholar
13	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
14	Baranwal S and Alahari SK: miRNA control of tumor cell invasion and metastasis. Int J Cancer. 126:1283–1290. 2010.
15	Rathod SS, Rani SB, Khan M, Muzumdar D and Shiras A: Tumor suppressive miRNA-34a suppresses cell proliferation and tumor growth of glioma stem cells by targeting Akt and Wnt signaling pathways. FEBS Open Bio. 4:485–495. 2014. View Article : Google Scholar : PubMed/NCBI
16	Pencheva N and Tavazoie SF: Control of metastatic progression by microRNA regulatory networks. Nat Cell Biol. 15:546–554. 2013. View Article : Google Scholar : PubMed/NCBI
17	Ell B, Qiu Q, Wei Y, Mercatali L, Ibrahim T, Amadori D and Kang Y: The microRNA-23b/27b/24 cluster promotes breast cancer lung metastasis by targeting metastasis-suppressive gene prosaposin. J Biol Chem. 289:21888–21895. 2014. View Article : Google Scholar : PubMed/NCBI
18	Gu Y, Cheng Y, Song Y, Zhang Z, Deng M, Wang C, Zheng G and He Z: MicroRNA-493 suppresses tumor growth, invasion and metastasis of lung cancer by regulating E2F1. PLoS One. 9:e1026022014. View Article : Google Scholar : PubMed/NCBI
19	Skinner HD, Lee JH, Bhutani MS, Weston B, Hofstetter W, Komaki R, Shiozaki H, Wadhwa R, Sudo K, Elimova E, et al: A validated miRNA profile predicts response to therapy in esophageal adenocarcinoma. Cancer. 120:3635–3641. 2014. View Article : Google Scholar : PubMed/NCBI
20	Tumilson CA, Lea RW, Alder JE and Shaw L: Circulating microRNA biomarkers for glioma and predicting response to therapy. Mol Neurobiol. 50:545–558. 2014. View Article : Google Scholar : PubMed/NCBI
21	Saito Y, Suzuki H, Imaeda H, Matsuzaki J, Hirata K, Tsugawa H, Hibino S, Kanai Y, Saito H and Hibi T: The tumor suppressor microRNA-29c is downregulated and restored by celecoxib in human gastric cancer cells. Int J Cancer. 132:1751–1760. 2013. View Article : Google Scholar
22	Wang J, Zhang J, Wu J, Luo D, Su K, Shi W, Liu J, Tian Y and Wei L: MicroRNA-610 inhibits the migration and invasion of gastric cancer cells by suppressing the expression of vasodilator-stimulated phosphoprotein. Eur J Cancer. 48:1904–1913. 2012. View Article : Google Scholar
23	Oh HK, Tan AL, Das K, Ooi CH, Deng NT, Tan IB, Beillard E, Lee J, Ramnarayanan K, Rha SY, et al: Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer. Clin Cancer Res. 17:2657–2667. 2011. View Article : Google Scholar : PubMed/NCBI
24	Yu S, Liu Y, Wang J, Guo Z, Zhang Q, Yu F, Zhang Y, Huang K, Li Y, Song E, et al: Circulating microRNA profiles as potential biomarkers for diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab. 97:2084–2092. 2012. View Article : Google Scholar : PubMed/NCBI
25	Etheridge A, Lee I, Hood L, Galas D and Wang K: Extracellular microRNA: a new source of biomarkers. Mutat Res. 717:85–90. 2011. View Article : Google Scholar : PubMed/NCBI
26	Cortez MA, Welsh JW and Calin GA: Circulating microRNAs as noninvasive biomarkers in breast cancer. Recent Results Cancer Res. 195:151–161. 2012. View Article : Google Scholar : PubMed/NCBI
27	Yip L, Kelly L, Shuai Y, Armstrong MJ, Nikiforov YE, Carty SE and Nikiforova MN: MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma. Ann Surg Oncol. 18:2035–2041. 2011. View Article : Google Scholar : PubMed/NCBI
28	Fassina A, Cappellesso R, Simonato F, Siri M, Ventura L, Tosato F, Busund LT, Pelizzo MR and Fassan M: A 4-MicroRNA signature can discriminate primary lymphomas from anaplastic carcinomas in thyroid cytology smears. Cancer Cytopathol. 122:274–281. 2014. View Article : Google Scholar
29	Nikiforova MN, Tseng GC, Steward D, Diorio D and Nikiforov YE: MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab. 93:1600–1608. 2008. View Article : Google Scholar : PubMed/NCBI
30	Hébrant A, Dom G, Dewaele M, Andry G, Trésallet C, Leteurtre E, Dumont JE and Maenhaut C: mRNA expression in papillary and anaplastic thyroid carcinoma: molecular anatomy of a killing switch. PLoS One. 7:e378072012. View Article : Google Scholar : PubMed/NCBI
31	Lee JC, Zhao JT, Clifton-Bligh RJ, Gill A, Gundara JS, Ip JC, Glover A, Sywak MS, Delbridge LW, Robinson BG and Sidhu SB: MicroRNA-222 and microRNA-146b are tissue and circulating biomarkers of recurrent papillary thyroid cancer. Cancer. 119:4358–4365. 2013. View Article : Google Scholar : PubMed/NCBI
32	Ruggeri RM, Campennì A, Baldari S, Trimarchi F and Trovato M: What is New on Thyroid Cancer Biomarkers. Biomark Insights. 3:237–252. 2008.PubMed/NCBI
33	He M, Zhao Y, Yi H, Sun H, Liu X and Ma S: The combination of TP53INP1, TP53INP2 and AXIN2: potential biomarkers in papillary thyroid carcinoma. Endocrine. 48:712–720. 2015. View Article : Google Scholar
34	Liu X, He M, Hou Y, Liang B, Zhao L, Ma S, Yu Y and Liu X: Expression profiles of microRNAs and their target genes in papillary thyroid carcinoma. Oncol Rep. 29:1415–1420. 2013.PubMed/NCBI
35	He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, et al: The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA. 102:19075–19080. 2005. View Article : Google Scholar : PubMed/NCBI
36	Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, Chiappetta G, Liu CG, Santoro M, Negrini M, et al: MicroRNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer. 13:497–508. 2006. View Article : Google Scholar : PubMed/NCBI
37	Shen R, Liyanarachchi S, Li W, Wakely PE Jr, Saji M, Huang J, Nagy R, Farrell T, Ringel MD, de la Chapelle A, et al: MicroRNA signature in thyroid fine needle aspiration cytology applied to 'atypia of undetermined significance' cases. Thyroid. 22:9–16. 2012. View Article : Google Scholar :
38	Gharib H: Changing trends in thyroid practice: understanding nodular thyroid disease. Endocr Pract. 10:31–39. 2004. View Article : Google Scholar : PubMed/NCBI
39	Prasad NB, Somervell H, Tufano RP, Dackiw AP, Marohn MR, Califano JA, Wang Y, Westra WH, Clark DP, Umbricht CB, et al: Identification of genes differentially expressed in benign versus malignant thyroid tumors. Clin Cancer Res. 14:3327–3337. 2008. View Article : Google Scholar : PubMed/NCBI
40	American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer; Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, et al: Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 19:1167–1214. 2009. View Article : Google Scholar : PubMed/NCBI