(2012-2016) – Principal Investigator for IVN Anca Botezatu, PhD

Aim: Improvement of the diagnostic and follow-up protocols of differentiated thyroid cancer with new markers for a better treatment outcome, prognosis and quality of life           

Partners: Coordinator: “C.I. PARHON” NATIONAL INSTITUTE OF ENDOCRINOLOGY project director Prf Corin Badiu, PhD

Partner 1 – „Stefan S. Nicolau” Institute of Virology, responsible Anca Botezatu, PhD

Partner 2 – „ THE INSTITUTE OF CELLULAR BIOLOGY AND PATHOLOGY N. SIMIONESCU, responsible Felicia Antohe PhD

Partner 3 – Agilrom Scientific, responsible, Ana Maria Niculescu

Working team: Botezatu A, Plesa A, Brasoveanu L, Iancu I, Huica I, Mihaila M, Bostan M

Funding: IVN=700 000 LEI

Project PNCDI2- 35-2012

Implementation period: dec.2012 – dec.2016

Summary: The concept of this project is to find genetic, epigenetic and protein molecular markers that can be predictors for formation and progression of thyroid differentiated cancer by investigating, in a multidisciplinary consortium, a representative group of Romanian population with this pathology. The study aims also to analyze the actual state of thyroid differentiated carcinoma in Romania, its prevalence regarding age, sex and regions in Romania.

The recent thyroid cancer management guidelines published by the American Thyroid Association (ATA) recommend a rather individualized management approach. ATA guidelines associate postoperative staging based on the clinical-pathological AJCC/UICC staging system with a novel, still not validated classification, comprising low, intermediate and high risk stratification, in order to assess risk for recurrence and mortality and allow early therapeutic decision making regarding radioactive iodine ablation and degree of TSH suppression. In low-risk and in intermediate/high-risk subjects, the risk stratification can be early achieved by clinical, biological and imagistic ongoing assessment within the first two years of follow-up.

Specific objectives:

– Determining the prevalence of differentiated thyroid carcinoma (DTC) in Romanian population according to age, sex and geographical area;

– Determining the prevalence of BRAF, RAS mutations and RET/PTC1, RET/PTC3 rearrangements, in differentiated thyroid carcinoma patients in Romanian Population;

– Identification of methylated genes associated to formation, progression and treatment response in differentiated thyroid carcinoma;

– Establishing the miRNA specific profiling in differentiated thyroid carcinoma;

– Identification of a specific panel of protein markers for differentiated thyroid carcinoma (altered gene products, angiogenesis markers);

– Setting-up of a Thyroid cancer register based on existing platform BIOMAT-ENDO;

– Setting-up biological samples collections (tumor, nucleic acids, blood samples);

– Setting-up of a personalized microarray chip for genes involved in tumorigenesis and progression of differentiated thyroid carcinoma.

Results:

1. Iulia Iancu, Irina Huica, Anca Botezatu, Adriana Plesa, Andreea Brehar, Dana Manda, Corin Badiu. Metilarea promotorului unor gene tumor-supresoare in cancerul tiroidian. Conferința Societății Române de Radioterapie și Zilele Medicale ale Institutului Oncologic “Prof. Dr. Alexandru Trestioreanu” București 31 Octombrie – 2 Noiembrie 2013, București’
2. Andreea Brehar, Camelia Procopiuc, Diana Paun, Dana Manda,Sabina Oros, Andra Caragheorgheopol, Alexandra Bulgar, Felix Brehar, Adriana Plesa, Iulia Iancu, Anca Botezatu, Mircea Ghemigian, Bogdan Stanescu, Daniel Brasoveanu, Dana Terzea,Dumitru Ioachim, Cristina Dumitrescu, Iuliana Gherlan, Corin Badiu, Constantin Dumitrache.  Methylation status of HOXB4 gene in papillary thyroid carcinoma. DOI: 10.1530/endoabs.35. Conference: 16th European Congress of Endocrinology, At Wroclaw, Poland, Abstract publicat in: Endocrine Abstracts 2014, 35 P1100 ISSN 1470-3947 (print)ISSN 1479-6848 (online)
3. Suzana Vladoiu, Sabina E. Oros, Sorina Schipor, Dana Manda, Andra Caragheorgheopol, D. Ioachim, M. Ghemigian, B. Stanescu, D. Brașoveanu, Roxana Roșca, Anca Botezatu, Andreea Brehar, Mirela Diana Ilie, Iulia Iancu, Adriana Pleșa, Irina Huica, Gabriela Anton, C. Badiu. Prevalenta mutatiei Braf V600E in cancerul papilar tiroidian. Al IX-lea Congres al Asociației de Endocrinologie Clinică din România 03-06 septembrie 2014, Sibiu
4. Andreea Brehar, Dana Manda, Sabina Oros, Andra Caragheorgheopol, Suzana Vlădoiu, Camelia Procopiuc, Alexandra Bulgar, F. Brehar, Diana Păun, Adriana Plesa, Iulia Iancu, Anca Botezatu, M. Ghemigian, B. Stănescu, D. Brașoveanu, Dana Terzea, D. Ioachim, Cristina Dumitrescu, Iuliana Gherlan, C. Badiu, C. Dumitrache. Evaluarea statusului de metilare a genei HOXB4 în carcinomul papilar tiroidian– rezultate preliminarii – Al IX-lea Congres al Asociației de Endocrinologie Clinică din România 03-06 septembrie 2014, Sibiu
5. Adriana Pleşa, Iulia Iancu, Anca Botezatu, Irina Huica, Dana Manda, Suzana Vladoiu, Gabriela Anton, Corin Badiu . Analyses of microRNA-34b and c-myc expression profile in papillary thyroid carcinoma. FEBS EMBO 2014 Conference, Paris (France) 30 August-4 September 2014, in FEBS Journal 281 (Suppl. 1) p 262. ISSN:1742-464X eISSN: 1742-4658. IF=5.622
6. Iulia Iancu, Adriana Pleşa, Anca Botezatu, Irina Huica, Gabriela Anton, Dana Manda, Andreea Brehar, Corin Badiu. Global DNA methylation evaluation and DNMT1 gene expression in thyroid neoplasia. FEBS EMBO 2014 Conference, Paris (France) 30 August-4 September 2014, in FEBS Journal 281 (Suppl. 1) p 302. ISSN:1742-464X eISSN: 1742-4658. IF=5.622
7. Botezatu A, Iancu IV, Manda D, Pleşa A, Huica I, Vladoiu S, Anton G, Badiu C. DNA methylation profiles of tumor suppressor genes promoters involved in papillary thyroid carcinoma. European cancer Congress 2015, 24-29 sept, Viena Austria, P 133
8. Pleşa A, Iancu IV, Botezatu A, Huica I, Manda D, Vladoiu S, Anton G, Badiu C. Expression profile of microRNA-34b, -21 and -133a in thyroid carcinoma. EACR Conference Series, Berlin, Germany – Basis epigenetic mechanisms in cancer. 8-11 nov, 2015, P30.
9. Iancu IV, Botezatu A, Pleşa A, Huica I, Anton G, Vladoiu S, Manda D. PTCSC3 and MEG3 IncRNAs expression profile in papillary thyroid carcinoma. EACR Conference Series, Berlin, Germany – Basis epigenetic mechanisms in cancer. 8-11 nov, 2015, P16.
10. Iancu IV, Botezatu A, Pleşa A, Huica I, Vladoiu S, Manda D, Badiu C. Long non-coding RNAs (MALAT 1 and MEG3) expression profiles in papillary thyroid carcinoma. EMBO/EMBL Symposium: The non-coding genome. EMBL Advanced training centre, Heidelberg, Germany, 18-21 oct 2015, pg192.
11. Botezatu A, Iancu IV, Popa O, Pleşa A, Manda D, Huica I, Vladoiu S, Anton G, Badiu C  New aspects in molecular and cellular mechanisms of human carcinogenesis -Mechanisms of oncogene activation, Book edited by: Dmitry Bulgin ISBN 978-953-51-4382-6, Publisher: InTech,  ISBN 978-953-51-2253-1, febr 2016
12. Adriana Pleşa, Iulia Virginia Iancu, Anca Botezatu, Irina Huică, Dana Manda, Susana Vlădoiu, Gabriela Anton, Corin Badiu. microRNA-34b, -21 and -133a expression pattern in thyroid carcinoma. European Human Genetics Conference (ESHG) 2016, Barcelona, Spain, abstract în European Journal of Human Genetics, vol 24-E supp 1, 2016, pp 480, E-P17.10. ISSN: 1018-4813, IF= 5.351