MicroRNA profiling predicts positive nodal status in papillary thyroid carcinoma in the preoperative setting.
Biomarkers, Tumor
/ genetics
Carcinoma, Papillary
/ genetics
Ceruletide
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Lymphatic Metastasis
/ genetics
MicroRNAs
/ genetics
Proto-Oncogene Proteins B-raf
/ genetics
Receptors, Cholecystokinin
/ genetics
Receptors, LHRH
/ genetics
Thyroid Cancer, Papillary
/ genetics
Thyroid Neoplasms
/ diagnosis
biomarkers
cytology
lymph node metastases
miRNA
papillary thyroid carcinoma
Journal
Cancer cytopathology
ISSN: 1934-6638
Titre abrégé: Cancer Cytopathol
Pays: United States
ID NLM: 101499453
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
02
04
2022
received:
08
02
2022
accepted:
04
04
2022
pubmed:
3
5
2022
medline:
20
9
2022
entrez:
2
5
2022
Statut:
ppublish
Résumé
The molecular characterization of thyroid nodules in cytological samples has so far been focused on discriminating between benign and malignant forms in a purely diagnostic setting. The evidence on the impact of molecular biomarkers to determine the risk of aggressiveness in cytologically "neoplastic" lesions is limited to genomic alterations (such as BRAF and TERT mutations). The aim of our study was to assess the preoperative role of microRNAs (miRNAs) in predicting the nodal status of patients with papillary thyroid cancer. A pilot series of histological samples of papillary thyroid carcinoma with (6 cases) or without (6 cases) lymph node metastases, matched for other major clinical and pathological features, was analyzed for global miRNA expression in a screening phase. A set of miRNAs was then validated in a series of 63 consecutive cytological samples of papillary carcinomas: 48 pN-negative and 15 pN-positive at histology. Unsupervised cluster analysis segregated surgical pN-negative and pN-positive samples, except for 1 case. The 45 differentially expressed miRNAs in pN-positive versus pN-negative cases were predicted to regulate a wide range of cellular pathways, enriched for Wnt, gonadotropin-releasing hormone receptor, and cerulein/cholecystokinin receptor signaling. In agreement with their profiles in surgical samples, 4 miRNAs of the 10 selected for validation (miR-154-3p, miR-299-5p, miR-376a-3p, and miR-302E) had a significant differential expression in cytological samples of papillary carcinoma with lymph node metastases and predicted the positive nodal status with a relatively good performance. MiRNA profiling is a potential promising strategy to define papillary carcinoma aggressiveness in the preoperative setting.
Sections du résumé
BACKGROUND
The molecular characterization of thyroid nodules in cytological samples has so far been focused on discriminating between benign and malignant forms in a purely diagnostic setting. The evidence on the impact of molecular biomarkers to determine the risk of aggressiveness in cytologically "neoplastic" lesions is limited to genomic alterations (such as BRAF and TERT mutations). The aim of our study was to assess the preoperative role of microRNAs (miRNAs) in predicting the nodal status of patients with papillary thyroid cancer.
METHODS
A pilot series of histological samples of papillary thyroid carcinoma with (6 cases) or without (6 cases) lymph node metastases, matched for other major clinical and pathological features, was analyzed for global miRNA expression in a screening phase. A set of miRNAs was then validated in a series of 63 consecutive cytological samples of papillary carcinomas: 48 pN-negative and 15 pN-positive at histology.
RESULTS
Unsupervised cluster analysis segregated surgical pN-negative and pN-positive samples, except for 1 case. The 45 differentially expressed miRNAs in pN-positive versus pN-negative cases were predicted to regulate a wide range of cellular pathways, enriched for Wnt, gonadotropin-releasing hormone receptor, and cerulein/cholecystokinin receptor signaling. In agreement with their profiles in surgical samples, 4 miRNAs of the 10 selected for validation (miR-154-3p, miR-299-5p, miR-376a-3p, and miR-302E) had a significant differential expression in cytological samples of papillary carcinoma with lymph node metastases and predicted the positive nodal status with a relatively good performance.
CONCLUSIONS
MiRNA profiling is a potential promising strategy to define papillary carcinoma aggressiveness in the preoperative setting.
Substances chimiques
Biomarkers, Tumor
0
MIRN154 microRNA, human
0
MIRN299 microRNA, human
0
MIRN376A1 microRNA, human
0
MicroRNAs
0
Receptors, Cholecystokinin
0
Receptors, LHRH
0
Ceruletide
888Y08971B
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
695-704Informations de copyright
© 2022 American Cancer Society.
Références
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;26:1-133.
Patel SG, Carty SE, Lee AJ. Molecular testing for thyroid nodules including its interpretation and use in clinical practice. Ann Surg Oncol.2021;28:8884-8891.
Censi S, Barollo S, Grespan E, et al. Prognostic significance of TERT promoter and BRAF mutations in TIR-4 and TIR-5 thyroid cytology. Eur J Endocrinol.2019;181:1-11.
Dell'Aquila M, Fiorentino V, Martini M, et al. How limited molecular testing can also offer diagnostic and prognostic evaluation of thyroid nodules processed with liquid-based cytology: role of TERT promoter and BRAF V600E mutation analysis. Cancer Cytopathol.2021;129:819-829.
Labourier E, Fahey TJ3rd.Preoperative molecular testing in thyroid nodules with Bethesda VI cytology: clinical experience and review of the literature. Diagn Cytopathol.2021;49:E175-E180.
Nakao T, Matsuse M, Saenko V, et al. Preoperative detection of the TERT promoter mutations in papillary thyroid carcinomas. Clin Endocrinol (Oxf).2021;95:790-799.
Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell.2014;159:676-690.
Hitu L, Gabora K, Bonci EA, et al. MicroRNA in papillary thyroid carcinoma: a systematic review from 2018 to June 2020. Cancers (Basel). 2020;12:3118.
Chengfeng X, Gengming C, Junjia Z, Yunxia L. MicroRNA signature predicts survival in papillary thyroid carcinoma. J Cell Biochem.2019;120:17050-17058.
Aragon Han P, Weng CH, Khawaja HT, et al. MicroRNA expression and association with clinicopathologic features in papillary thyroid cancer: a systematic review. Thyroid.2015;25:1322-1329.
Chou CK, Yang KD, Chou FF, et al. Prognostic implications of miR-146b expression and its functional role in papillary thyroid carcinoma. J Clin Endocrinol Metab.2013;98:E196-E205.
Yu C, Zhang L, Luo D, et al. MicroRNA-146b-3p promotes cell metastasis by directly targeting NF2 in human papillary thyroid cancer. Thyroid.2018;28:1627-1641.
Zhang M, Wu W, Gao M, Fei Z. MicroRNA-451 as a prognostic marker for diagnosis and lymph node metastasis of papillary thyroid carcinoma. Cancer Biomark.2017;19:437-445.
Liu Y, Li L, Liu Z, Yuan Q, Lu X. Downregulation of MiR-431 expression associated with lymph node metastasis and promotes cell invasion in papillary thyroid carcinoma. Cancer Biomark.2018;22:727-732.
Liu C, Xing M, Wang L, Zhang K. miR-199a-3p downregulation in thyroid tissues is associated with invasion and metastasis of papillary thyroid carcinoma. Br J Biomed Sci. 2017;74:90-94.
Wang M, Li R, Zou X, et al. A miRNA-clinicopathological nomogram for the prediction of central lymph node metastasis in papillary thyroid carcinoma-analysis from TCGA database. Medicine (Baltimore). 2020;99:e21996.
Han PA, Kim HS, Cho S, et al. Association of BRAF V600E mutation and microRNA expression with central lymph node metastases in papillary thyroid cancer: a prospective study from four endocrine surgery centers. Thyroid.2016;26:532-542.
Chen YT, Kitabayashi N, Zhou XK, Fahey TJ3rd, Scognamiglio T. MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma. Mod Pathol.2008;21:1139-1146.
Kitano M, Rahbari R, Patterson EE, et al. Evaluation of candidate diagnostic microRNAs in thyroid fine-needle aspiration biopsy samples. Thyroid.2012;22:285-291.
Benjamin H, Schnitzer-Perlman T, Shtabsky A, et al. Analytical validity of a microRNA-based assay for diagnosing indeterminate thyroid FNA smears from routinely prepared cytology slides. Cancer Cytopathol.2016;124:711-721.
Mazeh H, Deutch T, Karas A, et al. Next-generation sequencing identifies a highly accurate miRNA panel that distinguishes well-differentiated thyroid cancer from benign thyroid nodules. Cancer Epidemiol Biomarkers Prev.2018;27:858-863.
Castagna MG, Marzocchi C, Pilli T, Forleo R, Pacini F, Cantara S. MicroRNA expression profile of thyroid nodules in fine-needle aspiration cytology: a confirmatory series. J Endocrinol Invest.2019;42:97-100.
Silaghi CA, Lozovanu V, Georgescu CE, et al. Thyroseq v3, Afirma GSC, and microRNA panels versus previous molecular tests in the preoperative diagnosis of indeterminate thyroid nodules: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2021;12:649522.
Labourier E, Shifrin A, Busseniers AE, et al. Molecular testing for miRNA, mRNA, and DNA on fine-needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology. J Clin Endocrinol Metab.2015;100:2743-2750.
Titov SE, Kozorezova ES, Demenkov PS, et al. Preoperative typing of thyroid and parathyroid tumors with a combined molecular classifier. Cancers (Basel). 2021;13:237.
Saiselet M, Gacquer D, Spinette A, et al. New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer. BMC Genomics.2015;16:828.
Pallante P, Battista S, Pierantoni GM, Fusco A. Deregulation of microRNA expression in thyroid neoplasias. Nat Rev Endocrinol.2014;10:88-101.
Dai D, Tan Y, Guo L, Tang A, Zhao Y. Identification of exosomal miRNA biomarkers for diagnosis of papillary thyroid cancer by small RNA sequencing. Eur J Endocrinol.2020;182:111-121.
Lin S, Tan L, Luo D, Peng X, Zhu Y, Li H. Linc01278 inhibits the development of papillary thyroid carcinoma by regulating miR-376c-3p/DNM3 axis. Cancer Manag Res.2019;11:8557-8569.
Feng Z, Chen R, Huang N, Luo C. 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.2020;244:117298.
Wang W, Xia S, Zhan W. The long non-coding RNA ENST00000489676 influences papillary thyroid cancer cell. proliferation and invasion through regulating MiR-922. J Cancer.2019;10:5434-5446.
Wu C, Ma L, Wei H, Nie F, Ning J, Jiang T. MiR-1256 inhibits cell proliferation and cell cycle progression in papillary thyroid cancer by targeting 5-hydroxy tryptamine receptor 3A. Hum Cell.2020;33:630-640.
Kong W, Yang L, Li PP, et al. MiR-381-3p inhibits proliferation, migration and invasion by targeting LRP6 in papillary thyroid carcinoma. Eur Rev Med Pharmacol Sci.2018;22:3804-3811.
Zhao Z, Yang F, Liu Y, Fu K, Jing S. MicroRNA-409-3p suppresses cell proliferation and cell cycle progression by targeting cyclin D2 in papillary thyroid carcinoma. Oncol Lett.2018;16:5237-5242.
Wang Z, He L, Sun W, et al. miRNA-299-5p regulates estrogen receptor alpha and inhibits migration and invasion of papillary thyroid cancer cell. Cancer Manag Res.2018;10:6181-6193.
Omur O, Baran Y. An update on molecular biology of thyroid cancers. Crit Rev Oncol Hematol.2014;90:233-252.
Khoo ML, Beasley NJ, Ezzat S, Freeman JL, Asa SL. Overexpression of cyclin D1 and underexpression of p27 predict lymph node metastases in papillary thyroid carcinoma. J Clin Endocrinol Metab.2002;87:1814-1818.
Zhang J, Gill AJ, Issacs JD, et al. The Wnt/β-catenin pathway drives increased cyclin D1 levels in lymph node metastasis in papillary thyroid cancer. Hum Pathol.2012;43:1044-1050.
Wen D, Liao T, Ma B, et al. Downregulation of CSN6 attenuates papillary thyroid carcinoma progression by reducing Wnt/β-catenin signaling and sensitizes cancer cells to FH535 therapy. Cancer Med.2018;7:285-296.
Išić Denčić T, Bartolome A, Šelemetjev S, et al. High expression and localization of β-catenin and epidermal growth factor receptor identify high risk papillary thyroid carcinoma patients. Exp Mol Pathol.2018;105:181-189.
Wang N, Jiang R, Yang JY, et al. Expression of TGF-β1, SNAI1 and MMP-9 is associated with lymph node metastasis in papillary thyroid carcinoma. J Mol Histol.2014;45:391-399.
Zhang J, Tian XJ, Xing J. Signal transduction pathways of EMT induced by TGF-β, SHH, and WNT and their crosstalks. J Clin Med.2016;5:41.
Zhang J, Wang P, Dykstra M, et al. Platelet-derived growth factor receptor-α promotes lymphatic metastases in papillary thyroid cancer. J Pathol.2012;228:241-250.
Tang C, Yang L, Wang N, et al. High expression of GPER1, EGFR and CXCR1 is associated with lymph node metastasis in papillary thyroid carcinoma. Int J Clin Exp Pathol.2014;7:3213-3223.
Ekpe-Adewuyi E, Lopez-Campistrous A, Tang X, Brindley DN, McMullen TP. Platelet derived growth factor receptor alpha mediates nodal metastases in papillary thyroid cancer by driving the epithelial-mesenchymal transition. Oncotarget.2016;7:83684-83700.
Šelemetjev S, Bartolome A, Išić Denčić T, et al. Overexpression of epidermal growth factor receptor and its downstream effector, focal adhesion kinase, correlates with papillary thyroid carcinoma progression. Int J Exp Pathol.2018;99:87-94.
Yu B, Lv X, Su L, et al. MiR-148a Functions as a tumor suppressor by targeting CCK-BR via inactivating STAT3 and Akt in human gastric cancer. PLoS One.2016;11:e0158961.
Griffin MJ, Baik FM, Brandwein-Weber M, et al. Positive lymph node counts in American Thyroid Association low-risk papillary thyroid carcinoma patients. World J Surg.2020;44:1892-1897.