MicroRNA Profiling in Papillary Thyroid Cancer

被引:5
作者
Armos, Richard [1 ,2 ]
Bojtor, Bence [1 ]
Papp, Marton [3 ]
Illyes, Ildiko [4 ]
Lengyel, Balazs [1 ]
Kiss, Andras [1 ,4 ]
Szili, Balazs [1 ]
Tobias, Balint [1 ,2 ]
Balla, Bernadett [2 ]
Piko, Henriett [1 ]
Illes, Anett [1 ]
Putz, Zsuzsanna [1 ,2 ]
Toth, Erika [5 ]
Takacs, Istvan [1 ]
Kosa, Janos P. [1 ,2 ]
Lakatos, Peter [1 ,2 ]
机构
[1] Semmelweis Univ, Fac Med, Dept Med & Oncol, H-1083 Budapest, Hungary
[2] SE HUN REN TK ENDOMOLPAT Res Grp, H-1085 Budapest, Hungary
[3] Univ Vet Med, Ctr Bioinformat, H-1078 Budapest, Hungary
[4] Semmelweis Univ, Fac Med, Dept Pathol Forens & Insurance Med, H-1091 Budapest, Hungary
[5] Natl Inst Oncol, Dept Surg & Mol Pathol, H-1122 Budapest, Hungary
关键词
miRNA; papillary thyroid carcinoma; thyroid cancer; miRNA pattern; sequencing; molecular diagnostics; EXPRESSION; CARCINOMA; BIOMARKERS; NODULES; MIRNAS; CELLS;
D O I
10.3390/ijms25179362
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Genetic alterations are well known to be related to the pathogenesis and prognosis of papillary thyroid carcinoma (PTC). Some miRNA expression dysregulations have previously been described in the context of cancer development including thyroid carcinoma. In our study, we performed original molecular diagnostics on tissue samples related to our own patients. We aimed to identify all dysregulated miRNAs in potential association with PTC development via sequencing much higher numbers of control-matched PTC tissue samples and analyzing a wider variety of miRNA types than previous studies. We analyzed the expression levels of 2656 different human miRNAs in the context of 236 thyroid tissue samples (118 tumor and control pairs) related to anonymized PTC cases. Also, KEGG pathway enrichment analysis and GO framework analysis were used to establish the links between miRNA dysregulation and certain biological processes, pathways of signaling, molecular functions, and cellular components. A total of 30 significant differential miRNA expressions with at least +/- 1 log2 fold change were found related to PTC including, e.g., miR-551b, miR-146b, miR-221, miR-222, and miR-375, among others, being highly upregulated, as well as miR-873 and miR-204 being downregulated. In addition, we identified miRNA patterns in vast databases (KEGG and GO) closely similar to that of PTC including, e.g., miRNA patterns of prostate cancer, HTLV infection, HIF-1 signaling, cellular responses to growth factor stimulus and organic substance, and negative regulation of gene expression. We also found 352 potential associations between certain miRNA expressions and states of clinicopathological variables. Our findings-supported by the largest case number of original matched-control PTC-miRNA relation research-suggest a distinct miRNA expression profile in PTC that could contribute to a deeper understanding of the underlying molecular mechanisms promoting the pathogenesis of the disease. Moreover, significant miRNA expression deviations and their signaling pathways in PTC presented in our study may serve as potential biomarkers for PTC diagnosis and prognosis or even therapeutic targets in the future.
引用
收藏
页数:21
相关论文
共 69 条
[1]   Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis [J].
Ab Mutalib, Nurul-Syakima ;
Othman, Sri Noraima ;
Yusof, Azliana Mohamad ;
Suhaimi, Shahrun Niza Abdullah ;
Muhammad, Rohaizak ;
Jamal, Rahman .
PEERJ, 2016, 4
[2]   Papillary Thyroid Cancer: Genetic Alterations and Molecular Biomarker Investigations [J].
Abdullah, Mardiaty Iryani ;
Junit, Sarni Mat ;
Ng, Khoon Leong ;
Jayapalan, Jaime Jacqueline ;
Karikalan, Barani ;
Hashim, Onn Haji .
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, 2019, 16 (03) :450-460
[3]   Integrated Genomic Characterization of Papillary Thyroid Carcinoma [J].
Agrawal, Nishant ;
Akbani, Rehan ;
Aksoy, B. Arman ;
Ally, Adrian ;
Arachchi, Harindra ;
Asa, Sylvia L. ;
Auman, J. Todd ;
Balasundaram, Miruna ;
Balu, Saianand ;
Baylin, Stephen B. ;
Behera, Madhusmita ;
Bernard, Brady ;
Beroukhim, Rameen ;
Bishop, Justin A. ;
Black, Aaron D. ;
Bodenheimer, Tom ;
Boice, Lori ;
Bootwalla, Moiz S. ;
Bowen, Jay ;
Bowlby, Reanne ;
Bristow, Christopher A. ;
Brookens, Robin ;
Brooks, Denise ;
Bryant, Robert ;
Buda, Elizabeth ;
Butterfield, Yaron S. N. ;
Carling, Tobias ;
Carlsen, Rebecca ;
Carter, Scott L. ;
Carty, Sally E. ;
Chan, Timothy A. ;
Chen, Amy Y. ;
Cherniack, Andrew D. ;
Cheung, Dorothy ;
Chin, Lynda ;
Cho, Juok ;
Chu, Andy ;
Chuah, Eric ;
Cibulskis, Kristian ;
Ciriello, Giovanni ;
Clarke, Amanda ;
Clayman, Gary L. ;
Cope, Leslie ;
Copland, John A. ;
Covington, Kyle ;
Danilova, Ludmila ;
Davidsen, Tanja ;
Demchok, John A. ;
DiCara, Daniel ;
Dhalla, Noreen .
CELL, 2014, 159 (03) :676-690
[4]   The Gene Ontology knowledgebase in 2023 [J].
Aleksander, Suzi A. ;
Balhoff, James ;
Carbon, Seth ;
Cherry, J. Michael ;
Drabkin, Harold J. ;
Ebert, Dustin ;
Feuermann, Marc ;
Gaudet, Pascale ;
Harris, Nomi L. ;
Hill, David P. ;
Lee, Raymond ;
Mi, Huaiyu ;
Moxon, Sierra ;
Mungall, Christopher J. ;
Muruganugan, Anushya ;
Mushayahama, Tremayne ;
Sternberg, Paul W. ;
Thomas, Paul D. ;
Van Auken, Kimberly ;
Ramsey, Jolene ;
Siegele, Deborah A. ;
Chisholm, Rex L. ;
Fey, Petra ;
Aspromonte, Maria Cristina ;
Nugnes, Maria Victoria ;
Quaglia, Federica ;
Tosatto, Silvio ;
Giglio, Michelle ;
Nadendla, Suvarna ;
Antonazzo, Giulia ;
Attrill, Helen ;
dos Santos, Gil ;
Marygold, Steven ;
Strelets, Victor ;
Tabone, Christopher J. ;
Thurmond, Jim ;
Zhou, Pinglei ;
Ahmed, Saadullah H. ;
Asanitthong, Praoparn ;
Luna Buitrago, Diana ;
Erdol, Meltem N. ;
Gage, Matthew C. ;
Ali Kadhum, Mohamed ;
Li, Kan Yan Chloe ;
Long, Miao ;
Michalak, Aleksandra ;
Pesala, Angeline ;
Pritazahra, Armalya ;
Saverimuttu, Shirin C. C. ;
Su, Renzhi .
GENETICS, 2023, 224 (01)
[5]  
Almukhtar ZK, 2022, OPEN ACCESS MACED J, V10, P79, DOI DOI 10.3889/OAMJMS.2022.8059
[6]  
Ambros V., 2004, miRNAs Found by Genomics and Reverse Genetics Internet
[7]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[8]   Serum miR-551b-3p is a potential diagnostic biomarker for gastric cancer [J].
Bai, Su-yang ;
Ji, Rui ;
Wei, Hui ;
Guo, Qing-hong ;
Yuan, Hao ;
Chen, Zhao-feng ;
Wang, Yu-ping ;
Liu, Zheng ;
Yang, Xiao-yan ;
Zhou, Yong-ning .
TURKISH JOURNAL OF GASTROENTEROLOGY, 2019, 30 (05) :415-419
[9]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[10]   BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study [J].
Bertol, Bruna C. C. ;
Massaro, Juliana D. D. ;
Debortoli, Guilherme ;
Santos, Andre L. P. ;
de Araujo, Jessica N. G. ;
Giorgenon, Tatiana M. V. ;
Silva, Matheus ;
de Figueiredo-Feitosa, Nathalie L. ;
Collares, Cristhianna V. A. ;
de Freitas, Luiz Carlos C. ;
Soares, Edson G. G. ;
Neder, Luciano ;
Silbiger, Vivian N. N. ;
Calado, Rodrigo T. T. ;
Maciel, Lea M. Z. ;
Donadi, Eduardo A. A. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (15)