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Identification of circulating biomarkers for differentiating patients with papillary thyroid cancers from benign thyroid tumors

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Abstract

Background

This study aimed to identify the potential circulating biomarkers of protein, mRNAs, and long non-coding RNAs (lncRNAs) to differentiate the papillary thyroid cancers from benign thyroid tumors.

Methods

The study population of 100 patients was classified into identification (10 patients with papillary thyroid cancers and 10 patients with benign thyroid tumors) and validation groups (45 patients with papillary thyroid cancers and 35 patients with benign thyroid tumors). The Sengenics Immunome Protein Array-combined data mining approach using the Open Targets Platform was used to identify the putative protein biomarkers, and their expression validated using the enzyme-linked immunosorbent assay. Next-generation sequencing by Illumina HiSeq was used for the detection of dysregulated mRNAs and lncRNAs. The website Timer v2.0 helped identify the putative mRNA biomarkers, which were significantly over-expressed in papillary thyroid cancers than in adjacent normal thyroid tissue. The mRNA and lncRNA biomarker expression was validated by a real-time polymerase chain reaction.

Results

Although putative protein and mRNA biomarkers have been identified, their serum expression could not be confirmed in the validation cohorts. In addition, seven lncRNAs (TCONS_00516490, TCONS_00336559, TCONS_00311568, TCONS_00321917, TCONS_00336522, TCONS_00282483, and TCONS_00494326) were identified and validated as significantly downregulated in patients with papillary thyroid cancers compared to those with benign thyroid tumors. These seven lncRNAs showed moderate accuracy based on the area under the curve (AUC = 0.736) of receiver operating characteristic in predicting the occurrence of papillary thyroid cancers.

Conclusions

We identified seven downregulated circulating lncRNAs with the potential for predicting the occurrence of papillary thyroid cancers.

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Data availability

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

References

  1. Bomeli SR, LeBeau SO, Ferris RL (2010) Evaluation of a thyroid nodule. Otolaryngol Clin North Am 43:229–238

    Article  PubMed  PubMed Central  Google Scholar 

  2. Mazeh H, Beglaibter N, Prus D, Ariel I, Freund HR (2007) Cytohistologic correlation of thyroid nodules. Am J Surg 194:161–163

    Article  PubMed  Google Scholar 

  3. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L (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(2016):1–133

    Google Scholar 

  4. Paschou SA, Vryonidou A, Goulis DG (2017) Thyroid nodules: alpha guide to assessment, treatment and follow-up. Maturitas 96:1–9

    Article  PubMed  Google Scholar 

  5. Bhuiyan MM, Machowski A (2015) Nodular thyroid disease and thyroid malignancy: experience at Polokwane Mankweng Hospital Complex, Limpopo Province, South Africa. S Afr Med J 105:570–572

    Article  CAS  PubMed  Google Scholar 

  6. Doubi A, Al-Qannass A, Al-Angari SS, Al-Qahtani KH, Alessa M, Al-Dhahri S (2019) Trends in thyroid carcinoma among thyroidectomy patients: a 12-year multicenter study. Ann Saudi Med 39:345–349

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lawal O, Agbakwuru A, Olayinka OS, Adelusola K (2001) Thyroid malignancy in endemic nodular goitres: prevalence, pattern and treatment. Eur J Surg Oncol 27:157–161

    Article  CAS  PubMed  Google Scholar 

  8. Gorbea E, Goldrich DY, Agarwal J, Nayak R, Iloreta AM (2020) The impact of surgeon volume on total thyroidectomy outcomes among otolaryngologists. Am J Otolaryngol 41:102726

    Article  PubMed  Google Scholar 

  9. Lee DJ, Chin CJ, Hong CJ, Perera S, Witterick IJ (2018) Outpatient versus inpatient thyroidectomy: a systematic review and meta-analysis. Head Neck 40:192–202

    Article  PubMed  Google Scholar 

  10. Padur AA, Kumar N, Guru A, Badagabettu SN, Shanthakumar SR, Virupakshamurthy MB, Patil J (2016) Safety and effectiveness of total thyroidectomy and its comparison with subtotal thyroidectomy and other thyroid surgeries: a systematic review. Journal of thyroid research 2016:7594615

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Paduraru DN, Ion D, Carsote M, Andronic O, Bolocan A (2019) Post-thyroidectomy hypocalcemia—risk factors and management. Chirurgia (Bucur) 114:564–570

    Article  Google Scholar 

  12. Pan JH, Zhou H, Zhao XX, Ding H, Wei L, Qin L, Pan YL (2017) Robotic thyroidectomy versus conventional open thyroidectomy for thyroid cancer: a systematic review and meta-analysis. Surg Endosc 31:3985–4001

    Article  PubMed  Google Scholar 

  13. Gallo M, Pesenti M, Valcavi R (2003) Ultrasound thyroid nodule measurements: the “gold standard” and its limitations in clinical decision making. Endocrine Practice: Off J Am College Endocrinol Am Assoc Clin Endocrinol 9:194–199

    Article  Google Scholar 

  14. McCaffrey TV (2000) Evaluation of the thyroid nodule. Cancer Control: J Moffitt Cancer Center 7:223–228

    Article  CAS  Google Scholar 

  15. Mistry R, Hillyar C, Nibber A, Sooriyamoorthy T, Kumar N (2020) Ultrasound classification of thyroid nodules: a systematic review. Cureus 12:e7239

    PubMed  PubMed Central  Google Scholar 

  16. Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedüs L, Vitti P (2010) American association of clinical endocrinologists Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules. Endocrine Practice: Off J Am College Endocrinol Am Assoc Clin Endocrinol 16(Suppl 1):1–43

    Article  Google Scholar 

  17. Anil G, Hegde A, Chong FH (2011) Thyroid nodules: risk stratification for malignancy with ultrasound and guided biopsy. Cancer Imaging: Off Publ Int Cancer Imaging Soc 11:209–223

    Google Scholar 

  18. Hasukic B, Jakubovic-Cickusic A, Sehanovic E, Osmic H (2019) Fine needle aspiration cytology and thyroglobulin antibodies in preoperative diagnosis of thyroid malignancy. Med Arch (Sarajevo, Bosnia and Herzegovina) 73:382–385

    Google Scholar 

  19. Frates MC, Benson CB, Charboneau JW, Cibas ES, Clark OH, Coleman BG, Cronan JJ, Doubilet PM, Evans DB, Goellner JR, Hay ID, Hertzberg BS, Intenzo CM, Jeffrey RB, Langer JE, Larsen PR, Mandel SJ, Middleton WD, Reading CC, Sherman SI, Tessler FN (2005) Management of thyroid nodules detected at US: society of radiologists in ultrasound consensus conference statement. Radiology 237:794–800

    Article  PubMed  Google Scholar 

  20. Jackson BS (2018) Controversy regarding when clinically suspicious thyroid nodules should be subjected to surgery: review of current guidelines. Medicine (Baltimore) 97:e13634

    Article  Google Scholar 

  21. Chang JW, Shih CL, Wang CL, Luo JD, Wang CW, Hsieh JJ, Yu CJ, Chiou CC (2020) Transcriptomic analysis in liquid biopsy identifies circulating PCTAIRE-1 mRNA as a biomarker in NSCLC. Cancer Genomics Proteomics 17:91–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang R, Wu Y, Yu J, Yang G, Yi H, Xu B (2020) Plasma messenger RNAs identified through bioinformatics analysis are novel, non-invasive prostate cancer biomarkers. OncoTargets Therapy 13:541–548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Otandault A, Anker P, Al Amir Dache Z, Guillaumon V, Meddeb R, Pastor B, Pisareva E, Sanchez C, Tanos R, Tousch G, Schwarzenbach H, Thierry AR (2019) Recent advances in circulating nucleic acids in oncology. Ann Oncol 30:374–384

    Article  CAS  PubMed  Google Scholar 

  24. Le Rhun E, Seoane J, Salzet M, Soffietti R, Weller M (2020) Liquid biopsies for diagnosing and monitoring primary tumors of the central nervous system. Cancer Lett 480:24–28

    Article  PubMed  CAS  Google Scholar 

  25. Buschmann D, Haberberger A, Kirchner B, Spornraft M, Riedmaier I, Schelling G, Pfaffl MW (2016) Toward reliable biomarker signatures in the age of liquid biopsies—how to standardize the small RNA-Seq workflow. Nucleic Acids Res 44:5995–6018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. St Laurent G, Wahlestedt C, Kapranov P (2015) The landscape of long noncoding RNA classification. Trends Genet 31:239–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sanchez Calle A, Kawamura Y, Yamamoto Y, Takeshita F, Ochiya T (2018) Emerging roles of long non-coding RNA in cancer. Cancer Sci 109:2093–2100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mitra SA, Mitra AP, Triche TJ (2012) A central role for long non-coding RNA in cancer. Front Genet 3:17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Fatica A, Bozzoni I (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15:7–21

    Article  CAS  PubMed  Google Scholar 

  30. Hsieh CH, Hsu SY, Hsieh HY, Chen YC (2017) Differences between the sexes in motorcycle-related injuries and fatalities at a Taiwanese level I trauma center. Biomed J 40:113–120

    Article  PubMed  PubMed Central  Google Scholar 

  31. Hsieh CH, Liu HT, Hsu SY, Hsieh HY, Chen YC (2017) Motorcycle-related hospitalizations of the elderly. Biomed J 40:121–128

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hsieh CH, Chen YC, Hsu SY, Hsieh HY, Chien PC (2018) Defining polytrauma by abbreviated injury scale >/= 3 for a least two body regions is insufficient in terms of short-term outcome: a cross-sectional study at a level I trauma center. Biomed J 41:321–327

    Article  PubMed  PubMed Central  Google Scholar 

  33. Poulsen TBG, Damgaard D, Jørgensen MM, Senolt L, Blackburn JM, Nielsen CH, Stensballe A (2020) Identification of novel native autoantigens in rheumatoid arthritis. Biomedicines 8

  34. Soe HJ, Yong YK, Al-Obaidi MMJ, Raju CS, Gudimella R, Manikam R, Sekaran SD (2018) Identifying protein biomarkers in predicting disease severity of dengue virus infection using immune-related protein microarray. Medicine (Baltimore) 97:e9713

    Article  CAS  Google Scholar 

  35. Sumera A, Anuar ND, Radhakrishnan AK, Ibrahim H, Rutt NH, Ismail NH, Tan TM, Baba AA (2020) A novel method to identify autoantibodies against putative target proteins in serum from beta-thalassemia major: a pilot study. Biomedicines 8:97

    Article  CAS  PubMed Central  Google Scholar 

  36. Suwarnalata G, Tan AH, Isa H, Gudimella R, Anwar A, Loke MF, Mahadeva S, Lim SY, Vadivelu J (2016) Augmentation of autoantibodies by helicobacter pylori in Parkinson’s Disease patients may be linked to greater severity. PLoS ONE 11:e0153725

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Koscielny G, An P, Carvalho-Silva D, Cham JA, Fumis L, Gasparyan R, Hasan S, Karamanis N, Maguire M, Papa E, Pierleoni A, Pignatelli M, Platt T, Rowland F, Wankar P, Bento AP, Burdett T, Fabregat A, Forbes S, Gaulton A, Gonzalez CY, Hermjakob H, Hersey A, Jupe S, Kafkas Ş, Keays M, Leroy C, Lopez FJ, Magarinos MP, Malone J, McEntyre J, Munoz-Pomer Fuentes A, O’Donovan C, Papatheodorou I, Parkinson H, Palka B, Paschall J, Petryszak R, Pratanwanich N, Sarntivijal S, Saunders G, Sidiropoulos K, Smith T, Sondka Z, Stegle O, Tang YA, Turner E, Vaughan B, Vrousgou O, Watkins X, Martin MJ, Sanseau P, Vamathevan J, Birney E, Barrett J, Dunham I (2017) Open targets: a platform for therapeutic target identification and validation. Nucleic Acids Res 45:D985-d994

    Article  CAS  PubMed  Google Scholar 

  38. Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, Li B, Liu XS (2020) TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res 48:W509-w514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845

    Article  CAS  PubMed  Google Scholar 

  40. Akobeng AK (2007) Understanding diagnostic tests 3: receiver operating characteristic curves. Acta Paediatr 96:644–647

    Article  PubMed  Google Scholar 

  41. Discacciati A, Crippa A, Orsini N (2017) Goodness of fit tools for dose-response meta-analysis of binary outcomes. Res Synthesis Methods 8:149–160

    Article  Google Scholar 

  42. Doyle LM, Wang MZ (2019) Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells 8:727

    Article  CAS  PubMed Central  Google Scholar 

  43. Cao W, Zhou D, Tang W, An H, Zhang Y (2019) Discovery of plasma messenger RNA as novel biomarker for gastric cancer identified through bioinformatics analysis and clinical validation. PeerJ 7:e7025

    Article  PubMed  PubMed Central  Google Scholar 

  44. D’Avola D, Villacorta-Martin C, Martins-Filho SN, Craig A, Labgaa I, von Felden J, Kimaada A, Bonaccorso A, Tabrizian P, Hartmann BM, Sebra R, Schwartz M, Villanueva A (2018) High-density single cell mRNA sequencing to characterize circulating tumor cells in hepatocellular carcinoma. Sci Rep 8:11570

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Zhou D, Tang W, Liu X, An HX, Zhang Y (2017) Clinical verification of plasma messenger RNA as novel noninvasive biomarker identified through bioinformatics analysis for lung cancer. Oncotarget 8:43978–43989

    Article  PubMed  PubMed Central  Google Scholar 

  46. Chen Q, Zhu C, Jin Y, Si X, Jiao W, He W, Mao W, Li M, Luo G (2020) Plasma long non-coding RNA RP11–438N53 as a novel biomarker for non-small cell lung cancer. Cancer Manage Res 12:1513–1521

    Article  CAS  Google Scholar 

  47. Iempridee T, Wiwithaphon S, Piboonprai K, Pratedrat P, Khumkhrong P, Japrung D, Temisak S, Laiwejpithaya S, Chaopotong P, Dharakul T (2018) Identification of reference genes for circulating long noncoding RNA analysis in serum of cervical cancer patients. FEBS Open Bio 8:1844–1854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Shen X, Xue Y, Cong H, Wang X, Fan Z, Cui X, Ju S (2020) Circulating lncRNA DANCR as a potential auxillary biomarker for the diagnosis and prognostic prediction of colorectal cancer, Biosci Rep 40

  49. Takahashi K, Ota Y, Kogure T, Suzuki Y, Iwamoto H, Yamakita K, Kitano Y, Fujii S, Haneda M, Patel T, Ota T (2020) Circulating extracellular vesicle-encapsulated HULC is a potential biomarker for human pancreatic cancer. Cancer Sci 111:98–111

    Article  CAS  PubMed  Google Scholar 

  50. Wang J, Gao Y, Wang X, Gao Y, Li L, Zhang J, Zhang L, Che F (2020) Circulating lncRNAs as noninvasive biomarkers in bladder cancer: a diagnostic meta-analysis based on 15 published articles. Int J Biol Markers 35:40–48

    Article  PubMed  Google Scholar 

  51. Yao Y, Chen X, Lu S, Zhou C, Xu G, Yan Z, Yang J, Yu T, Chen W, Qian Y, Ding S, Tang J, Chen Y, Zhang Y (2018) Circulating Long noncoding RNAs as biomarkers for predicting head and neck squamous cell carcinoma. Cell Physiol Biochem 50:1429–1440

    Article  CAS  PubMed  Google Scholar 

  52. Mahmoudian-Sani MR, Jalali A, Jamshidi M, Moridi H, Alghasi A, Shojaeian A, Mobini GR (2019) Long non-coding RNAs in thyroid cancer: implications for pathogenesis, diagnosis, and therapy. Oncol Res Treatment 42:136–142

    Article  CAS  Google Scholar 

  53. Min X, Liu K, Zhu H, Zhang J (2018) Long noncoding RNA LINC003121 inhibits proliferation and invasion of thyroid cancer cells by suppression of the phosphatidylinositol-3-Kinase (PI3K)/Akt signaling pathway. Med Sci Monitor: Int Med J Exp Clin Res 24:4592–4601

    Article  CAS  Google Scholar 

  54. Qin L, Luo JZ, Tang XL, Han CG (2019) Identification of long noncoding RNA MIR22HG as a novel biomarker in thyroid cancer. Pathol Oncol Res 25:703–710

    Article  CAS  PubMed  Google Scholar 

  55. Gu Y, Feng C, Liu T, Zhang B, Yang L (2018) The downregulation of lncRNA EMX2OS might independently predict shorter recurrence-free survival of classical papillary thyroid cancer. PLoS ONE 13:e0209338

    Article  PubMed  PubMed Central  Google Scholar 

  56. Liu Y, Li J, Li F, Li M, Shao Y, Wu L (2019) SNHG15 functions as a tumor suppressor in thyroid cancer. J Cell Biochem 120:6120–6126

    Article  CAS  PubMed  Google Scholar 

  57. Zhang K, Lv J, Peng X, Liu J, Li C, Li J, Yin N, Li H, Li Z (2019) Down-regulation of DANCR acts as a potential biomarker for papillary thyroid cancer diagnosis. Biosci Rep 39

  58. Jiao X, Lu J, Huang Y, Zhang J, Zhang H, Zhang K (2019) Long non-coding RNA H19 may be a marker for prediction of prognosis in the follow-up of patients with papillary thyroid cancer. Cancer Biomarkers: Section A Disease Markers 26:203–207

    Article  CAS  Google Scholar 

  59. Zhou T, Zhong M, Zhang S, Wang Z, Xie R, Xiong C, Lv Y, Chen W, Yu J (2018) LncRNA CASC2 expression is down- regulated in papillary thyroid cancer and promotes cell invasion by affecting EMT pathway. Cancer Biomarkers: Section A Disease markers 23:185–191

    Article  CAS  Google Scholar 

  60. Shao L, Sun W, Wang Z, Dong W, Qin Y (2020) Long noncoding RNA SAMMSON promotes papillary thyroid carcinoma progression through p300/Sp1 axis and serves as a novel diagnostic and prognostic biomarker. IUBMB Life 72:237–246

    Article  CAS  PubMed  Google Scholar 

  61. Luzon-Toro B, Fernandez RM, Martos-Martinez JM, Rubio-Manzanares-Dorado M, Antinolo G, Borrego S (2019) LncRNA LUCAT1 as a novel prognostic biomarker for patients with papillary thyroid cancer. Sci Rep 9:14374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhang H, Cai Y, Zheng L, Zhang Z, Lin X, Jiang N (2018) LncRNA BISPR promotes the progression of thyroid papillary carcinoma by regulating miR-21-5p. Int J Immunopathol Pharmacol 32:2058738418772652

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Jiang L, Wu Z, Meng X, Chu X, Huang H, Xu C (2019) LncRNA HOXA-AS2 facilitates tumorigenesis and progression of papillary thyroid cancer by modulating the miR-15a-5p/HOXA3 Axis. Hum Gene Ther 30:618–631

    Article  CAS  PubMed  Google Scholar 

  64. Cui M, Chang Y, Du W, Liu S, Qi J, Luo R, Luo S (2018) Upregulation of lncRNA-ATB by transforming growth factor β1 (TGF-β1) promotes migration and invasion of papillary thyroid carcinoma cells. Med Sci Monitor: Int Med J Exp Clin Res 24:5152–5158

    Article  CAS  Google Scholar 

  65. Feng Z, Chen R, Huang N, Luo C (2020) Long non-coding RNA ASMTL-AS1 inhibits tumor growth and glycolysis by regulating the miR-93-3p/miR-660/FOXO1 axis in papillary thyroid carcinoma. Life Sci 244:117298

    Article  CAS  PubMed  Google Scholar 

  66. Li H, Han Q, Chen Y, Chen X, Ma R, Chang Q, Yin D (2019) Upregulation of the long non-coding RNA FOXD2-AS1 is correlated with tumor progression and metastasis in papillary thyroid cancer. Am J Trans Res 11:5457–5471

    CAS  Google Scholar 

  67. Li G, Kong Q (2019) LncRNA LINC00460 promotes the papillary thyroid cancer progression by regulating the LINC00460/miR-485-5p/Raf1 axis. Biol Res 52:61

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Song B, Li R, Zuo Z, Tan J, Liu L, Ding D, Lu Y, Hou D (2019) LncRNA ENST00000539653 acts as an oncogenic factor via MAPK signalling in papillary thyroid cancer. BMC Cancer 19:297

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the experimental support from the Genomic and Proteomic Core Laboratory, Kaohsiung Chang Gung Memorial Hospital.

Funding

This work was supported by Chang Gung Memorial Hospital CMRPG8I0451 & CMRPG8I0452 to Shun-Yu Chi supported this research.

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Author notes

  1. S.-C. Wu and S.-Y. Chi: equal contribution for first authorship.

Authors and Affiliations

  1. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, Taiwan

    S.-C. Wu

  2. Department of General Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, Taiwan

    S.-Y. Chi

  3. Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, Taiwan

    C.-S. Rau

  4. Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No.123, Ta-Pei Road, Niao-Song District, Kaohsiung City 833, Taiwan

    P.-J. Kuo, L.-H. Huang, Y.-C. Wu, C.-J. Wu, H.-P. Lin & C.-H. Hsieh

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Contributions

Writing—original draft: C-SR; writing—review and proof-reading: S-CW; surgery and specimen collection: S-YC; writing—tables and figures: P-JK; experiment (protein array and ELISA): L-HH; experiment (NGS): Y-CW; experiment (real-time PCR): C-JW; collection of medical data and specimen: H-PL; conceptualization, bioinformatic analysis and data interpretation: C-HH; all authors read and approved the final manuscript.

Corresponding author

Correspondence to C.-H. Hsieh.

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The authors declare that they have no competing interests.

Ethical approval and consent to participate

This study was pre-approved by the Institutional Review Board (IRB) of Chang Gung Memorial Hospital (approved number: 201801437B0). All patients read and signed the consent form before the collection of the blood samples.

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Supplementary Information

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40618_2021_1543_MOESM1_ESM.xlsx

Supplementary file1 (XLSX 19 KB) Table 1. Significantly-dysregulated mRNAs determined by next-generation sequencing in the serum of patients with papillary thyroid cancers compared to those with benign thyroid tumors

40618_2021_1543_MOESM2_ESM.xlsx

Supplementary file2 (XLSX 18 KB) Table 2. Annotation and sequence information of the significantly-dysregulated lncRNAs determined by next-generation sequencing in the serum of patients with papillary thyroid cancers compared to those with benign thyroid tumors

40618_2021_1543_MOESM3_ESM.xlsx

Supplementary file3 (XLSX 14 KB) Table 3. Association of the significantly-dysregulated lncRNAs determined by next-generation sequencing with the patient characteristics

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Wu, SC., Chi, SY., Rau, CS. et al. Identification of circulating biomarkers for differentiating patients with papillary thyroid cancers from benign thyroid tumors. J Endocrinol Invest 44, 2375–2386 (2021). https://doi.org/10.1007/s40618-021-01543-2

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