Blood biomarkers in differentiated thyroid cancer: current status and advances_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

GAO Xu , YU Qing’an , YAN Xiao ,  DAI Wenjie

Department of Thyroid Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, P. R. China;

Corresponding author：

DAI Wenjie, Email: davidhmu@163.com

Keywords：

differentiated thyroid cancer; blood marker; thyroglobulin; liquid biospy

DOI：

10.7507/1007-9424.202102059

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective In order to improve the levels of clinical diagnosis and treatment of differentiated thyroid cancer, the research status and progress of blood markers of differentiated thyroid cancer in recent years were reviewed.Method The literatures about blood markers and liquid biopsy of differentiated thyroid cancer at home and abroad in recent years were searched and summarized.Results Thyroglobulin and thyroglobulin antibody were the most commonly used for markers of differentiated thyroid cancer. The application value of blood markers such as microRNA and long non-coding RNA in the diagnosis, treatment and follow-up of differentiated thyroid cancer had also been found.Conclusion Because of the advantages of high specificity, high sensitivity, and no-invasion, blood markers are useful indicators to help improve the diagnosis of thyroid cancer patients and monitor the disease progression and recurrence in the future.

Citation： GAO Xu, YU Qing’an, YAN Xiao, DAI Wenjie. Blood biomarkers in differentiated thyroid cancer: current status and advances. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(1): 118-123. doi: 10.7507/1007-9424.202102059 Copy

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2.	Evans C, Tennant S, Perros P. Serum thyroglobulin in the monitoring of differentiated thyroid cancer. Scand J Clin Lab Invest Suppl, 2016, 245: S119-S123.
3.	Spencer C, Petrovic I, Fatemi S. Current thyroglobulin autoantibody (TgAb) assays often fail to detect interfering TgAb that can result in the reporting of falsely low/undetectable serum Tg IMA values for patients with differentiated thyroid cancer. J Clin Endocrinol Metab, 2011, 96(5): 1283-1291.
4.	Netzel BC, Grebe SK, Carranza Leon BG, et al. Thyroglobulin (Tg) testing revisited: Tg assays, TgAb assays, and correlation of results with clinical outcomes. J Clin Endocrinol Metab, 2015, 100(8): E1074-E1083.
5.	Azmat U, Porter K, Senter L, et al. Thyroglobulin liquid chromatography-tandem mass spectrometry has a low sensitivity for detecting structural disease in patients with antithyroglobulin antibodies. Thyroid, 2017, 27(1): 74-80.
6.	Shuford CM, Johnson JS, Thompson JW, et al. More sensitivity is always better: measuring sub-clinical levels of serum thyroglobulin on a μLC–MS/MS system. Clinical Mass Spectrometry, 2020, 15: 29-35.
7.	Verburg FA, Luster M, Cupini C, et al. Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement. Thyroid, 2013, 23(10): 1211-1225.
8.	Haugen BR, Alexander EK, Bible KC, 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, 2016, 26(1): 1-133.
9.	Kars A, Aktan B, Kilic K, et al. Preoperative serum thyroglobulin level as a useful predictive marker to differentiate thyroid cancer. ORL J Otorhinolaryngol Relat Spec, 2018, 80(5-6): 290-295.
10.	Kim H, Park SY, Choe JH, et al. Preoperative serum thyroglobulin and its correlation with the burden and extent of differentiated thyroid cancer. Cancers (Basel), 2020, 12(3): 625.
11.	Kim H, Kim YN, Kim HI, et al. Preoperative serum thyroglobulin predicts initial distant metastasis in patients with differentiated thyroid cancer. Sci Rep, 2017, 7(1): 16955.
12.	Patell R, Mikhael A, Tabet M, et al. Assessing the utility of preoperative serum thyroglobulin in differentiated thyroid cancer: a retrospective cohort study. Endocrine, 2018, 61(3): 506-510.
13.	Huang Z, Song M, Wang S, et al. Preoperative serum thyroglobulin is a risk factor of skip metastasis in papillary thyroid carcinoma. Ann Transl Med, 2020, 8(6): 389.
14.	Yu Q, Liu K, Xie C, et al. Development and validation of a preoperative prediction model for follicular thyroid carcinoma. Clin Endocrinol (Oxf), 2019, 91(2): 348-355.
15.	Spencer CA. Clinical review: Clinical utility of thyroglobulin antibody (TgAb) measurements for patients with differentiated thyroid cancers (DTC). J Clin Endocrinol Metab, 2011, 96(12): 3615-3627.
16.	Kim ES, Lim DJ, Baek KH, et al. Thyroglobulin antibody is associated with increased cancer risk in thyroid nodules. Thyroid, 2010, 20(8): 885-891.
17.	Phan HT, Jager PL, van der Wal JE, et al. The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation. Eur J Endocrinol, 2008, 158(1): 77-83.
18.	Tsushima Y, Miyauchi A, Ito Y, et al. Prognostic significance of changes in serum thyroglobulin antibody levels of pre- and post-total thyroidectomy in thyroglobulin antibody-positive papillary thyroid carcinoma patients. Endocr J, 2013, 60(7): 871-876.
19.	Durante C, Tognini S, Montesano T, et al. Clinical aggressiveness and long-term outcome in patients with papillary thyroid cancer and circulating anti-thyroglobulin autoantibodies. Thyroid, 2014, 24(7): 1139-1145.
20.	Lee ZJO, Eslick GD, Edirimanne S. Investigating antithyroglobulin antibody as a prognostic marker for differentiated thyroid cancer: a meta-analysis and systematic review. Thyroid, 2020, 30(11): 1601-1612.
21.	Albano D, Tulchinsky M, Dondi F, et al. Thyroglobulin doubling time offers a better threshold than thyroglobulin level for selecting optimal candidates to undergo localizing ¹⁸F FDG PET/CT in non-iodine avid differentiated thyroid carcinoma. Eur J Nucl Med Mol Imaging, 2021, 48(2): 461-468.
22.	Landenberger GMC, de Souza Salerno ML, Golbert L, et al. Thyroglobulin antibodies as a prognostic factor in papillary thyroid carcinoma patients with indeterminate response after initial therapy. Horm Metab Res, 2021, 53(2): 94-99.
23.	Côrtes MCS, Rosario PW, Oliveira LFF, et al. Clinical impact of detectable antithyroglobulin antibodies below the reference limit (borderline) in patients with papillary thyroid carcinoma with undetectable serum thyroglobulin and normal neck ultrasonography after ablation: a prospective study. Thyroid, 2018, 28(2): 229-235.
24.	Yin N, Sherman SI, Pak Y, et al. The de novo detection of anti-thyroglobulin antibodies and differentiated thyroid cancer recurrence. Thyroid, 2020, 30(10): 1490-1495.
25.	Scappaticcio L, Trimboli P, Verburg FA, et al. Significance of “de novo”appearance of thyroglobulin antibodies in patients with differentiated thyroid cancer. Int J Biol Markers, 2020, 35(3): 41-49.
26.	Gupta M, Taguba L, Arciaga R, et al. Detection of circulating thyroid cancer cells by reverse transcription-PCR for thyroid-stimulating hormone receptor and thyroglobulin: the importance of primer selection. Clin Chem, 2002, 48: 1862-1865.
27.	Aliyev A, Gupta M, Nasr C, et al. Circulating thyroid-stimulating hormone receptor messenger RNA as a marker of tumor aggressiveness in patients with papillary thyroid microcarcinoma. Endocr Pract, 2015, 21(7): 777-781.
28.	Milas M, Shin J, Gupta M, et al. Circulating thyrotropin receptor mRNA as a novel marker of thyroid cancer: clinical applications learned from 1 758 samples. Ann Surg, 2010, 252(4): 643-651.
29.	Aliyev A, Patel J, Brainard J, et al. Diagnostic accuracy of circulating thyrotropin receptor messenger RNA combined with neck ultrasonography in patients with Bethesda Ⅲ-Ⅴ thyroid cytology. Surgery, 2016, 159(1): 113-117.
30.	Li YR, Tseng CP, Hsu HL, et al. Circulating epithelial cells as potential biomarkers for detection of recurrence in patients of papillary thyroid carcinoma with positive serum anti-thyroglobulin antibody. Clin Chim Acta, 2018, 477: 74-80.
31.	Aliyev A, Soundararajan S, Bucak E, et al. The utility of peripheral thyrotropin receptor mRNA in the management of differentiated thyroid cancer. Surgery, 2015, 158(4): 1089-1093.
32.	Salido-Guadarrama I, Romero-Cordoba S, Peralta-Zaragoza O, et al. MicroRNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer. Onco Targets Ther, 2014, 7: 1327-1338.
33.	Lee YS, Lim YS, Lee JC, et al. Differential expression levels of plasma-derived miR-146b and miR-155 in papillary thyroid cancer. Oral Oncol, 2015, 51(1): 77-83.
34.	Rosignolo F, Sponziello M, Giacomelli L, et al. Identification of thyroid-associated serum microRNA profiles and their potential use in thyroid cancer follow-up. J Endocr Soc, 2017, 1(1): 3-13.
35.	Zhang Y, Pan J, Xu D, et al. Combination of serum microRNAs and ultrasound profile as predictive biomarkers of diagnosis and prognosis for papillary thyroid microcarcinoma. Oncol Rep, 2018, 40(6): 3611-3624.
36.	Yoruker EE, Terzioglu D, Teksoz S, et al. MicroRNA expression profiles in papillary thyroid carcinoma, benign thyroid nodules and healthy controls. J Cancer, 2016, 7(7): 803-809.
37.	Xu SL, Tian YY, Zhou Y, et al. Diagnostic value of circulating microRNAs in thyroid carcinoma: A systematic review and meta-analysis. Clin Endocrinol (Oxf), 2020, 93(4): 489-498.
38.	Samsonov R, Burdakov V, Shtam T, et al. Plasma exosomal miR-21 and miR-181a differentiates follicular from papillary thyroid cancer. Tumour Biol, 2016, 37(9): 12011-12021.
39.	Pan W, Zhou L, Ge M, et al. Whole exome sequencing identifies lncRNA GAS8-AS1 and LPAR4 as novel papillary thyroid carcinoma driver alternations. Hum Mol Genet, 2016, 25(9): 1875-1884.
40.	Zhang D, Liu X, Wei B, et al. Plasma lncRNA GAS8-AS1 as a potential biomarker of papillary thyroid carcinoma in chinese patients. Int J Endocrinol, 2017, 2017: 2645904.
41.	Cui M, Chang Y, Du W, et al. Upregulation of lncRNA-ATB by transforming growth factor β1 (TGF-β1) promotes migration and invasion of papillary thyroid carcinoma cells. Med Sci Monit, 2018, 24: 5152-5158.
42.	Wu L, Shi Y, Liu B, et al. Expression of lncRNA-HOTAIR in the serum of patients with lymph node metastasis of papillary thyroid carcinoma and its impact. Oncol Lett, 2020, 20(1): 907-913.
43.	Liu C, Chen T, Liu Z. Associations between BRAF^V600E and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis. World J Surg Oncol, 2016, 14(1): 241.
44.	Lubitz CC, Zhan T, Gunda V, et al. Circulating BRAF^V600E levels correlate with treatment in patients with thyroid carcinoma. Thyroid, 2018, 28(3): 328-339.
45.	Jensen K, Thakur S, Patel A, et al. Detection of BRAF^V600E in liquid biopsy from patients with papillary thyroid cancer is associated with tumor aggressiveness and response to therapy. J Clin Med, 2020, 9(8): 2481.
46.	Almubarak H, Qassem E, Alghofaili L, et al. Non-invasive molecular detection of minimal residual disease in papillary thyroid cancer patients. Front Oncol, 2020, 9: 1510.
47.	Tang W, Huang C, Tang C, et al. Galectin-3 may serve as a potential marker for diagnosis and prognosis in papillary thyroid carcinoma: a meta-analysis. Onco Targets Ther, 2016, 9: 455-460.
48.	Yılmaz E, Karşıdağ T, Tatar C, et al. Serum galectin-3: diagnostic value for papillary thyroid carcinoma. Ulus Cerrahi Derg, 2015, 31(4): 192-196.
49.	Du F, Liu S, Ma H, et al. The value of serum MK and Gal-3 in the diagnosis and prediction postoperative metastasis of thyroid cancer. JNM, 2019, 60(Suppl 1): 364-364.
50.	Zhao W, Ajani JA, Sushovan G, et al. Galectin-3 mediates tumor cell-stroma interactions by activating pancreatic stellate cells to produce cytokines via integrin signaling. Gastroenterology, 2018, 154(5): 1524-1537.
51.	Yu W, Ma B, Zhao W, et al. The combination of circRNA-UMAD1 and Galectin-3 in peripheral circulation is a co-biomarker for predicting lymph node metastasis of thyroid carcinoma. Am J Transl Res, 2020, 12(9): 5399-5415.
52.	Chen S, Wang M, Chen X, et al. In vitro expression of cytokeratin 19 in adipose-derived stem cells is induced by epidermal growth factor. Med Sci Monit, 2018, 24: 4254-4261.
53.	Giovanella L, Ceriani L, Ghelfo A, et al. Circulating cytokeratin 19 fragments in patients with benign nodules and carcinomas of the thyroid gland. Int J Biol Markers, Jan-Mar, 2008, 23(1): 54-57.
54.	Išić T, Savin S, Cvejić D, et al. Serum Cyfra 21.1 and galectin-3 protein levels in relation to immunohistochemical cytokeratin 19 and galectin-3 expression in patients with thyroid tumors. J Cancer Res Clin Oncol, 2010, 136(12): 1805-1812.
55.	Malapure SS, Patel CD, Lakshmy R, et al. Evaluation of CYFRA 21.1 as a dedifferentiation marker of advanced thyroid cancer. Indian J Nucl Med, Apr-Jun, 2020, 35(2): 116-121.
56.	Giovanella L, Imperiali M, Trimboli P. Role of serum cytokeratin 19 fragment (Cyfra 21.1) as a prognostic biomarker in patients with differentiated thyroid cancer. Sci Rep, 2017, 7(1): 7359.
57.	Fu L, Wang R, Yin L, et al. CYFRA21-1 tests in the diagnosis of non-small cell lung cancer: A meta-analysis. Int J Biol Markers, 2019, 34(3): 251-261.
58.	Jin C, Yang M, Han X, et al. Evaluation of the value of preoperative CYFRA21-1 in the diagnosis and prognosis of epithelial ovarian cancer in conjunction with CA125. J Ovarian Res, 2019, 12(1): 114.
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1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin, 2019, 69(1): 7-34.
2. Evans C, Tennant S, Perros P. Serum thyroglobulin in the monitoring of differentiated thyroid cancer. Scand J Clin Lab Invest Suppl, 2016, 245: S119-S123.
3. Spencer C, Petrovic I, Fatemi S. Current thyroglobulin autoantibody (TgAb) assays often fail to detect interfering TgAb that can result in the reporting of falsely low/undetectable serum Tg IMA values for patients with differentiated thyroid cancer. J Clin Endocrinol Metab, 2011, 96(5): 1283-1291.
4. Netzel BC, Grebe SK, Carranza Leon BG, et al. Thyroglobulin (Tg) testing revisited: Tg assays, TgAb assays, and correlation of results with clinical outcomes. J Clin Endocrinol Metab, 2015, 100(8): E1074-E1083.
5. Azmat U, Porter K, Senter L, et al. Thyroglobulin liquid chromatography-tandem mass spectrometry has a low sensitivity for detecting structural disease in patients with antithyroglobulin antibodies. Thyroid, 2017, 27(1): 74-80.
6. Shuford CM, Johnson JS, Thompson JW, et al. More sensitivity is always better: measuring sub-clinical levels of serum thyroglobulin on a μLC–MS/MS system. Clinical Mass Spectrometry, 2020, 15: 29-35.
7. Verburg FA, Luster M, Cupini C, et al. Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement. Thyroid, 2013, 23(10): 1211-1225.
8. Haugen BR, Alexander EK, Bible KC, 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, 2016, 26(1): 1-133.
9. Kars A, Aktan B, Kilic K, et al. Preoperative serum thyroglobulin level as a useful predictive marker to differentiate thyroid cancer. ORL J Otorhinolaryngol Relat Spec, 2018, 80(5-6): 290-295.
10. Kim H, Park SY, Choe JH, et al. Preoperative serum thyroglobulin and its correlation with the burden and extent of differentiated thyroid cancer. Cancers (Basel), 2020, 12(3): 625.
11. Kim H, Kim YN, Kim HI, et al. Preoperative serum thyroglobulin predicts initial distant metastasis in patients with differentiated thyroid cancer. Sci Rep, 2017, 7(1): 16955.
12. Patell R, Mikhael A, Tabet M, et al. Assessing the utility of preoperative serum thyroglobulin in differentiated thyroid cancer: a retrospective cohort study. Endocrine, 2018, 61(3): 506-510.
13. Huang Z, Song M, Wang S, et al. Preoperative serum thyroglobulin is a risk factor of skip metastasis in papillary thyroid carcinoma. Ann Transl Med, 2020, 8(6): 389.
14. Yu Q, Liu K, Xie C, et al. Development and validation of a preoperative prediction model for follicular thyroid carcinoma. Clin Endocrinol (Oxf), 2019, 91(2): 348-355.
15. Spencer CA. Clinical review: Clinical utility of thyroglobulin antibody (TgAb) measurements for patients with differentiated thyroid cancers (DTC). J Clin Endocrinol Metab, 2011, 96(12): 3615-3627.
16. Kim ES, Lim DJ, Baek KH, et al. Thyroglobulin antibody is associated with increased cancer risk in thyroid nodules. Thyroid, 2010, 20(8): 885-891.
17. Phan HT, Jager PL, van der Wal JE, et al. The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation. Eur J Endocrinol, 2008, 158(1): 77-83.
18. Tsushima Y, Miyauchi A, Ito Y, et al. Prognostic significance of changes in serum thyroglobulin antibody levels of pre- and post-total thyroidectomy in thyroglobulin antibody-positive papillary thyroid carcinoma patients. Endocr J, 2013, 60(7): 871-876.
19. Durante C, Tognini S, Montesano T, et al. Clinical aggressiveness and long-term outcome in patients with papillary thyroid cancer and circulating anti-thyroglobulin autoantibodies. Thyroid, 2014, 24(7): 1139-1145.
20. Lee ZJO, Eslick GD, Edirimanne S. Investigating antithyroglobulin antibody as a prognostic marker for differentiated thyroid cancer: a meta-analysis and systematic review. Thyroid, 2020, 30(11): 1601-1612.
21. Albano D, Tulchinsky M, Dondi F, et al. Thyroglobulin doubling time offers a better threshold than thyroglobulin level for selecting optimal candidates to undergo localizing ¹⁸F FDG PET/CT in non-iodine avid differentiated thyroid carcinoma. Eur J Nucl Med Mol Imaging, 2021, 48(2): 461-468.
22. Landenberger GMC, de Souza Salerno ML, Golbert L, et al. Thyroglobulin antibodies as a prognostic factor in papillary thyroid carcinoma patients with indeterminate response after initial therapy. Horm Metab Res, 2021, 53(2): 94-99.
23. Côrtes MCS, Rosario PW, Oliveira LFF, et al. Clinical impact of detectable antithyroglobulin antibodies below the reference limit (borderline) in patients with papillary thyroid carcinoma with undetectable serum thyroglobulin and normal neck ultrasonography after ablation: a prospective study. Thyroid, 2018, 28(2): 229-235.
24. Yin N, Sherman SI, Pak Y, et al. The de novo detection of anti-thyroglobulin antibodies and differentiated thyroid cancer recurrence. Thyroid, 2020, 30(10): 1490-1495.
25. Scappaticcio L, Trimboli P, Verburg FA, et al. Significance of “de novo”appearance of thyroglobulin antibodies in patients with differentiated thyroid cancer. Int J Biol Markers, 2020, 35(3): 41-49.
26. Gupta M, Taguba L, Arciaga R, et al. Detection of circulating thyroid cancer cells by reverse transcription-PCR for thyroid-stimulating hormone receptor and thyroglobulin: the importance of primer selection. Clin Chem, 2002, 48: 1862-1865.
27. Aliyev A, Gupta M, Nasr C, et al. Circulating thyroid-stimulating hormone receptor messenger RNA as a marker of tumor aggressiveness in patients with papillary thyroid microcarcinoma. Endocr Pract, 2015, 21(7): 777-781.
28. Milas M, Shin J, Gupta M, et al. Circulating thyrotropin receptor mRNA as a novel marker of thyroid cancer: clinical applications learned from 1 758 samples. Ann Surg, 2010, 252(4): 643-651.
29. Aliyev A, Patel J, Brainard J, et al. Diagnostic accuracy of circulating thyrotropin receptor messenger RNA combined with neck ultrasonography in patients with Bethesda Ⅲ-Ⅴ thyroid cytology. Surgery, 2016, 159(1): 113-117.
30. Li YR, Tseng CP, Hsu HL, et al. Circulating epithelial cells as potential biomarkers for detection of recurrence in patients of papillary thyroid carcinoma with positive serum anti-thyroglobulin antibody. Clin Chim Acta, 2018, 477: 74-80.
31. Aliyev A, Soundararajan S, Bucak E, et al. The utility of peripheral thyrotropin receptor mRNA in the management of differentiated thyroid cancer. Surgery, 2015, 158(4): 1089-1093.
32. Salido-Guadarrama I, Romero-Cordoba S, Peralta-Zaragoza O, et al. MicroRNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer. Onco Targets Ther, 2014, 7: 1327-1338.
33. Lee YS, Lim YS, Lee JC, et al. Differential expression levels of plasma-derived miR-146b and miR-155 in papillary thyroid cancer. Oral Oncol, 2015, 51(1): 77-83.
34. Rosignolo F, Sponziello M, Giacomelli L, et al. Identification of thyroid-associated serum microRNA profiles and their potential use in thyroid cancer follow-up. J Endocr Soc, 2017, 1(1): 3-13.
35. Zhang Y, Pan J, Xu D, et al. Combination of serum microRNAs and ultrasound profile as predictive biomarkers of diagnosis and prognosis for papillary thyroid microcarcinoma. Oncol Rep, 2018, 40(6): 3611-3624.
36. Yoruker EE, Terzioglu D, Teksoz S, et al. MicroRNA expression profiles in papillary thyroid carcinoma, benign thyroid nodules and healthy controls. J Cancer, 2016, 7(7): 803-809.
37. Xu SL, Tian YY, Zhou Y, et al. Diagnostic value of circulating microRNAs in thyroid carcinoma: A systematic review and meta-analysis. Clin Endocrinol (Oxf), 2020, 93(4): 489-498.
38. Samsonov R, Burdakov V, Shtam T, et al. Plasma exosomal miR-21 and miR-181a differentiates follicular from papillary thyroid cancer. Tumour Biol, 2016, 37(9): 12011-12021.
39. Pan W, Zhou L, Ge M, et al. Whole exome sequencing identifies lncRNA GAS8-AS1 and LPAR4 as novel papillary thyroid carcinoma driver alternations. Hum Mol Genet, 2016, 25(9): 1875-1884.
40. Zhang D, Liu X, Wei B, et al. Plasma lncRNA GAS8-AS1 as a potential biomarker of papillary thyroid carcinoma in chinese patients. Int J Endocrinol, 2017, 2017: 2645904.
41. Cui M, Chang Y, Du W, et al. Upregulation of lncRNA-ATB by transforming growth factor β1 (TGF-β1) promotes migration and invasion of papillary thyroid carcinoma cells. Med Sci Monit, 2018, 24: 5152-5158.
42. Wu L, Shi Y, Liu B, et al. Expression of lncRNA-HOTAIR in the serum of patients with lymph node metastasis of papillary thyroid carcinoma and its impact. Oncol Lett, 2020, 20(1): 907-913.
43. Liu C, Chen T, Liu Z. Associations between BRAF^V600E and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis. World J Surg Oncol, 2016, 14(1): 241.
44. Lubitz CC, Zhan T, Gunda V, et al. Circulating BRAF^V600E levels correlate with treatment in patients with thyroid carcinoma. Thyroid, 2018, 28(3): 328-339.
45. Jensen K, Thakur S, Patel A, et al. Detection of BRAF^V600E in liquid biopsy from patients with papillary thyroid cancer is associated with tumor aggressiveness and response to therapy. J Clin Med, 2020, 9(8): 2481.
46. Almubarak H, Qassem E, Alghofaili L, et al. Non-invasive molecular detection of minimal residual disease in papillary thyroid cancer patients. Front Oncol, 2020, 9: 1510.
47. Tang W, Huang C, Tang C, et al. Galectin-3 may serve as a potential marker for diagnosis and prognosis in papillary thyroid carcinoma: a meta-analysis. Onco Targets Ther, 2016, 9: 455-460.
48. Yılmaz E, Karşıdağ T, Tatar C, et al. Serum galectin-3: diagnostic value for papillary thyroid carcinoma. Ulus Cerrahi Derg, 2015, 31(4): 192-196.
49. Du F, Liu S, Ma H, et al. The value of serum MK and Gal-3 in the diagnosis and prediction postoperative metastasis of thyroid cancer. JNM, 2019, 60(Suppl 1): 364-364.
50. Zhao W, Ajani JA, Sushovan G, et al. Galectin-3 mediates tumor cell-stroma interactions by activating pancreatic stellate cells to produce cytokines via integrin signaling. Gastroenterology, 2018, 154(5): 1524-1537.
51. Yu W, Ma B, Zhao W, et al. The combination of circRNA-UMAD1 and Galectin-3 in peripheral circulation is a co-biomarker for predicting lymph node metastasis of thyroid carcinoma. Am J Transl Res, 2020, 12(9): 5399-5415.
52. Chen S, Wang M, Chen X, et al. In vitro expression of cytokeratin 19 in adipose-derived stem cells is induced by epidermal growth factor. Med Sci Monit, 2018, 24: 4254-4261.
53. Giovanella L, Ceriani L, Ghelfo A, et al. Circulating cytokeratin 19 fragments in patients with benign nodules and carcinomas of the thyroid gland. Int J Biol Markers, Jan-Mar, 2008, 23(1): 54-57.
54. Išić T, Savin S, Cvejić D, et al. Serum Cyfra 21.1 and galectin-3 protein levels in relation to immunohistochemical cytokeratin 19 and galectin-3 expression in patients with thyroid tumors. J Cancer Res Clin Oncol, 2010, 136(12): 1805-1812.
55. Malapure SS, Patel CD, Lakshmy R, et al. Evaluation of CYFRA 21.1 as a dedifferentiation marker of advanced thyroid cancer. Indian J Nucl Med, Apr-Jun, 2020, 35(2): 116-121.
56. Giovanella L, Imperiali M, Trimboli P. Role of serum cytokeratin 19 fragment (Cyfra 21.1) as a prognostic biomarker in patients with differentiated thyroid cancer. Sci Rep, 2017, 7(1): 7359.
57. Fu L, Wang R, Yin L, et al. CYFRA21-1 tests in the diagnosis of non-small cell lung cancer: A meta-analysis. Int J Biol Markers, 2019, 34(3): 251-261.
58. Jin C, Yang M, Han X, et al. Evaluation of the value of preoperative CYFRA21-1 in the diagnosis and prognosis of epithelial ovarian cancer in conjunction with CA125. J Ovarian Res, 2019, 12(1): 114.
59. Shin DH, Jo JY, Kim SH, et al. Midkine is a potential therapeutic target of tumorigenesis, angiogenesis, and metastasis in non-small cell lung cancer. Cancers (Basel), 2020, 12(9): 2402.
60. Ibrahim NA, Hamam AM. Role of midkine in predicting malignancy in patient with solitary thyroid nodule. JCTI, 2019, 9(2): 1-10.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Blood biomarkers in differentiated thyroid cancer: current status and advances

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