MicroRNA‑mRNA integrated analysis based on a case of well‑differentiated thyroid cancer with both metastasis and metastatic recurrence

Zhang,Yun‑Jie; Ma,Yu‑Shui; Xia,Qing; Yu,Fei; Lv,Zhong‑Wei; Jia,Cheng‑You; Jiang,Xiao‑Xin; Zhang,Liang; Shao,Yun‑Chao; Xie,Wen‑Ting; Lu,Gai‑Xia; Yv,Xia‑Qing; Zhong,Peng; Fu,Da; Wang,Xiao‑Feng

doi:10.3892/or.2018.6739

MicroRNA‑mRNA integrated analysis based on a case of well‑differentiated thyroid cancer with both metastasis and metastatic recurrence

Authors:
- Yun‑Jie Zhang
- Yu‑Shui Ma
- Qing Xia
- Fei Yu
- Zhong‑Wei Lv
- Cheng‑You Jia
- Xiao‑Xin Jiang
- Liang Zhang
- Yun‑Chao Shao
- Wen‑Ting Xie
- Gai‑Xia Lu
- Xia‑Qing Yv
- Peng Zhong
- Da Fu
- Xiao‑Feng Wang
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Affiliations: Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China, Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China, Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
Published online on: September 26, 2018 https://doi.org/10.3892/or.2018.6739
Pages: 3803-3811

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Abstract

The incidence of well‑differentiated thyroid cancer (WDTC) is rapidly increasing. Poor survival follows distant metastasis (DM) and recurrence. In the present study, we aimed to analyze the expression alterations in different stages of WDTC and the regulatory mechanism of DM and the recurrence of DM. A male patient diagnosed with follicular thyroid cancer and distant metastasis in the eleventh thoracic vertebrae received total thyroidectomy and the removal of a metastatic lesion. A local relapse was found in the vertebrae after four‑time iodine‑131 treatment. We performed mRNA and microRNA microarray on the paracancerous, cancerous, metastatic and metastatic recurrent tissue. In combination with the data of The Cancer Genome Atlas (TCGA), we used bioinformatics approaches to analyze the common alterations and microRNA‑mRNA interactions among the processes of tumorigenesis and metastasis. Metastatic lesions and recurrent lesions were used to investigate the molecular mechanism of tumor evolution and recurrence in this case. A total of four mRNAs and two microRNAs were newly found to be related to patient survival in WDTC. The microRNA‑mRNA interactions were predicted for the overlapped mRNAs and microRNAs. Lineage deregulation of genes, such as C‑X‑C motif chemokine receptor 4 (CXCR4) and thyroglobulin (TG) were found from the tumorigenic stage to the metastatic stage. The ribosome pathway was highly enriched in the bone metastasis compared with the cancerous tissue. The downstreaming effects of p53 were impaired in the recurrent lesion due to deregulation of several functional genes. The integrated analysis with TCGA data indicated several prognostic markers and regulatory networks for potential treatment. Our results also provided possible molecular mechanisms in which the ribosome and p53 pathways may respectively contribute to bone metastasis and local recurrence of metastasis.

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1	Kilfoy BA, Zheng T, Holford TR, Han X, Ward MH, Sjodin A, Zhang Y, Bai Y, Zhu C, Guo GL, et al: International patterns and trends in thyroid cancer incidence, 1973–2002. Cancer Causes Control. 20:525–531. 2009. View Article : Google Scholar : PubMed/NCBI
2	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
3	Sherman SI: Thyroid carcinoma. Lancet. 361:501–511. 2003. View Article : Google Scholar : PubMed/NCBI
4	Xing M, Haugen BR and Schlumberger M: Progress in molecular-based management of differentiated thyroid cancer. Lancet. 381:1058–1069. 2013. View Article : Google Scholar : PubMed/NCBI
5	Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE and Fagin JA: High prevalence of BRAF mutations in thyroid cancer: Genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res. 63:1454–1457. 2003.PubMed/NCBI
6	Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW and Sidransky D: BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 95:625–627. 2003. View Article : Google Scholar : PubMed/NCBI
7	Ciampi R, Knauf JA, Kerler R, Gandhi M, Zhu Z, Nikiforova MN, Rabes HM, Fagin JA and Nikiforov YE: Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. J Clin Invest. 115:94–101. 2005. View Article : Google Scholar : PubMed/NCBI
8	Wreesmann VB, Sieczka EM, Socci ND, Hezel M, Belbin TJ, Childs G, Patel SG, Patel KN, Tallini G, Prystowsky M, et al: Genome-wide profiling of papillary thyroid cancer identifies MUC1 as an independent prognostic marker. Cancer Res. 64:3780–3789. 2004. View Article : Google Scholar : PubMed/NCBI
9	Moon S, Song YS, Kim YA, Lim JA, Cho SW, Moon JH, Hahn S, Park DJ and Park YJ: Effects of coexistent BRAF^V600E and TERT promoter mutations on poor clinical outcomes in papillary thyroid cancer: A meta-analysis. Thyroid. 27:651–660. 2017. View Article : Google Scholar : PubMed/NCBI
10	Lee JJ, Wang TY, Liu CL, Chien MN, Chen MJ, Hsu YC, Leung CH and Cheng SP: Dipeptidyl peptidase IV as a prognostic marker and therapeutic target in papillary thyroid carcinoma. J Clin Endocrinol Metab. 102:2930–2940. 2017. View Article : Google Scholar : PubMed/NCBI
11	Chowdhury S, Veyhl J, Jessa F, Polyakova O, Alenzi A, MacMillan C, Ralhan R and Walfish PG: Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants. Oncotarget. 7:32318–32328. 2016. View Article : Google Scholar : PubMed/NCBI
12	Samaan NA, Schultz PN, Hickey RC, Goepfert H, Haynie TP, Johnston DA and Ordonez NG: The results of various modalities of treatment of well differentiated thyroid carcinomas: A retrospective review of 1599 patients. J Clin Endocrinol Metab. 75:714–720. 1992. View Article : Google Scholar : PubMed/NCBI
13	Schlumberger MJ: Papillary and follicular thyroid carcinoma. N Engl J Med. 338:297–306. 1998. View Article : Google Scholar : PubMed/NCBI
14	Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, Caillou B, Ricard M, Lumbroso JD, De Vathaire F, et al: Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: Benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 91:2892–2899. 2006. View Article : Google Scholar : PubMed/NCBI
15	Haugen BR: 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: What is new and what has changed? Cancer. 123:372–381. 2017. View Article : Google Scholar : PubMed/NCBI
16	O'Neill CJ, Oucharek J, Learoyd D and Sidhu SB: Standard and emerging therapies for metastatic differentiated thyroid cancer. Oncologist. 15:146–156. 2010. View Article : Google Scholar : PubMed/NCBI
17	Mazzaferri EL and Kloos RT: Clinical review 128: Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab. 86:1447–1463. 2001. View Article : Google Scholar : PubMed/NCBI
18	Mazzaferri EL and Jhiang SM: Differentiated thyroid cancer long-term impact of initial therapy. Trans Am Clin Climatol Assoc. 106(151–168): discussion 168–170. 1995.PubMed/NCBI
19	Visone R, Russo L, Pallante P, De Martino I, Ferraro A, Leone V, Borbone E, Petrocca F, Alder H, Croce CM and Fusco A: MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle. Endocr Relat Cancer. 14:791–798. 2007. View Article : Google Scholar : PubMed/NCBI
20	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
21	Cancer Genome Atlas Research Network: Integrated genomic characterization of papillary thyroid carcinoma. Cell. 159:676–690. 2014. View Article : Google Scholar : PubMed/NCBI
22	Zhao M, Wang KJ, Tan Z, Zheng CM, Liang Z and Zhao JQ: Identification of potential therapeutic targets for papillary thyroid carcinoma by bioinformatics analysis. Oncol Lett. 11:51–58. 2016. View Article : Google Scholar : PubMed/NCBI
23	Geraldo MV and Kimura ET: Integrated analysis of thyroid cancer public datasets reveals role of post-transcriptional regulation on tumor progression by targeting of immune system mediators. PLoS One. 10:e01417262015. View Article : Google Scholar : PubMed/NCBI
24	Dweep H and Gretz N: miRWalk2.0: A comprehensive atlas of microRNA-target interactions. Nat Methods. 12:6972015. View Article : Google Scholar : PubMed/NCBI
25	Betel D, Wilson M, Gabow A, Marks DS and Sander C: The microRNA.org resource: Targets and expression. Nucleic Acids Res. 36:D149–D153. 2008. View Article : Google Scholar : PubMed/NCBI
26	Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. Elife. 4:e050052015. View Article : Google Scholar :
27	Kanehisa M, Sato Y, Kawashima M, Furumichi M and Tanabe M: KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44:D457–D462. 2016. View Article : Google Scholar : PubMed/NCBI
28	Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al: Gene ontology: Tool for the unification of biology. The gene ontology consortium. Nat Genet. 25:25–29. 2000. View Article : Google Scholar : PubMed/NCBI
29	da Huang W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using david bioinformatics resources. Nat Protoc. 4:44–57. 2009. View Article : Google Scholar : PubMed/NCBI
30	Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W and Smyth GK: Limma powers differential expression analyses for rna-sequencing and microarray studies. Nucleic Acids Res. 43:e472015. View Article : Google Scholar : PubMed/NCBI
31	Benjamini Y and Hochberg Y: Controlling the false discovery rate-a practical and powerful approach to multiple testing. J R Stat Soc Ser B-Methodol. 57:289–300. 1995.
32	Le Pennec S, Konopka T, Gacquer D, Fimereli D, Tarabichi M, Tomas G, Savagner F, Decaussin-Petrucci M, Tresallet C, Andry G, et al: Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases. Endocr Relat Cancer. 22:205–216. 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	Lin RY: Thyroid cancer stem cells. Nat Rev Endocrinol. 7:609–616. 2011. View Article : Google Scholar : PubMed/NCBI
35	Takano T, Miyauchi A, Yokozawa T, Matsuzuka F, Maeda I, Kuma K and Amino N: Preoperative diagnosis of thyroid papillary and anaplastic carcinomas by real-time quantitative reverse transcription-polymerase chain reaction of oncofetal fibronectin messenger RNA. Cancer Res. 59:4542–4545. 1999.PubMed/NCBI
36	Are C and Shaha AR: Anaplastic thyroid carcinoma: Biology, pathogenesis, prognostic factors, and treatment approaches. Ann Surg Oncol. 13:453–464. 2006. View Article : Google Scholar : PubMed/NCBI
37	Hou Z, Meyer S, Propson NE, Nie J, Jiang P, Stewart R and Thomson JA: Characterization and target identification of a DNA aptamer that labels pluripotent stem cells. Cell Res. 25:390–393. 2015. View Article : Google Scholar : PubMed/NCBI
38	Rao SR, Snaith AE, Marino D, Cheng X, Lwin ST, Orriss IR, Hamdy FC and Edwards CM: Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer. Br J Cancer. 116:227–236. 2017. View Article : Google Scholar : PubMed/NCBI
39	Iwadate Y, Suganami A, Tamura Y, Matsutani T, Hirono S, Shinozaki N, Hiwasa T, Takiguchi M and Saeki N: The pluripotent stem-cell marker alkaline phosphatase is highly expressed in refractory glioblastoma with DNA hypomethylation. Neurosurgery. 80:248–256. 2017. View Article : Google Scholar : PubMed/NCBI
40	Vosa U, Vooder T, Kolde R, Vilo J, Metspalu A and Annilo T: Meta-analysis of microRNA expression in lung cancer. Int J Cancer. 132:2884–2893. 2013. View Article : Google Scholar : PubMed/NCBI
41	Tan X, Qin W, Zhang L, Hang J, Li B, Zhang C, Wan J, Zhou F, Shao K, Sun Y, et al: A 5-microRNA signature for lung squamous cell carcinoma diagnosis and hsa-miR-31 for prognosis. Clin Cancer Res. 17:6802–6811. 2011. View Article : Google Scholar : PubMed/NCBI
42	Zhang X, Zhang T, Yang K, Zhang M and Wang K: miR-486-5p suppresses prostate cancer metastasis by targeting Snail and regulating epithelial-mesenchymal transition. Onco Targets Ther. 9:6909–6914. 2016. View Article : Google Scholar : PubMed/NCBI
43	Burton A: Regulation of RANKL might reduce bone metastases. Lancet Oncol. 7:3672006. View Article : Google Scholar : PubMed/NCBI
44	Torregrossa L, Giannini R, Borrelli N, Sensi E, Melillo RM, Leocata P, Materazzi G, Miccoli P, Santoro M and Basolo F: Cxcr4 expression correlates with the degree of tumor infiltration and braf status in papillary thyroid carcinomas. Mod Pathol. 25:46–55. 2012. View Article : Google Scholar : PubMed/NCBI
45	Ponnusamy MP, Lakshmanan I, Jain M, Das S, Chakraborty S, Dey P and Batra SK: Muc4 mucin-induced epithelial to mesenchymal transition: A novel mechanism for metastasis of human ovarian cancer cells. Oncogene. 29:5741–5754. 2010. View Article : Google Scholar : PubMed/NCBI
46	Singh AP, Moniaux N, Chauhan SC, Meza JL and Batra SK: Inhibition of muc4 expression suppresses pancreatic tumor cell growth and metastasis. Cancer Res. 64:622–630. 2004. View Article : Google Scholar : PubMed/NCBI
47	Rowson-Hodel AR, Wald JH, Hatakeyama J, O'Neal WK, Stonebraker JR, VanderVorst K, Saldana MJ, Borowsky AD, Sweeney C and Carraway KL III: Membrane mucin muc4 promotes blood cell association with tumor cells and mediates efficient metastasis in a mouse model of breast cancer. Oncogene. 37:197–207. 2018. View Article : Google Scholar : PubMed/NCBI
48	Li W, Liu C, Zhao C, Zhai L and Lv S: Downregulation of β3 integrin by miR-30a-5p modulates cell adhesion and invasion by interrupting Erk/Ets-1 network in triple-negative breast cancer. Int J Oncol. 48:1155–1164. 2016. View Article : Google Scholar : PubMed/NCBI
49	Wei W, Yang Y, Cai J, Cui K, Li RX, Wang H, Shang X and Wei D: miR-30a-5p suppresses tumor metastasis of human colorectal cancer by targeting ITGB3. Cell Physiol Biochem. 39:1165–1176. 2016. View Article : Google Scholar : PubMed/NCBI
50	Chung YH, Li SC, Kao YH, Luo HL, Cheng YT, Lin PR, Tai MH and Chiang PH: miR-30a-5p inhibits epithelial-to-mesenchymal transition and upregulates expression of tight junction protein claudin-5 in human upper tract urothelial carcinoma cells. Int J Mol Sci. 18:E18262017. View Article : Google Scholar : PubMed/NCBI
51	Ruggero D and Pandolfi PP: Does the ribosome translate cancer? Nat Rev Cancer. 3:179–192. 2003. View Article : Google Scholar : PubMed/NCBI
52	Ma ZF and Skeaff SA: Thyroglobulin as a biomarker of iodine deficiency: A review. Thyroid. 24:1195–1209. 2014. View Article : Google Scholar : PubMed/NCBI
53	Vermeulen L, Sprick MR, Kemper K, Stassi G and Medema JP: Cancer stem cells-old concepts, new insights. Cell Death Differ. 15:947–958. 2008. View Article : Google Scholar : PubMed/NCBI