Project: Profiling radioREsistant Differentiated thyroId Cancer: genes, immunity, cancer stem cells and epithelial-mesenchymal transition
| Acronym | PREDICt (Reference Number: TRS-2018-00000721) |
| Duration | 01/04/2019 |
| Project Topic | Radioiodine-refractory (RAI-R) differentiated thyroid cancer (DTC) is a challenging tumor. Several mechanisms have been claimed for RAI-R. Hypothesis: RAI-R DTC have peculiar assets that underline resistance and differentiate these tumors from RAI-sensitive (RAI-S) ones. Aims: - Evaluate the genetic, trascriptomic profiles and the role of cancer stem cells (CSC), epithelial-mesenchymal transition (EMT) and immunity in RAI-R DTC; - Identify RAI-R DTC biomarkers; - Develop RAI-R DTC organoids. Methods: High risk DTC patients (pts) will be enrolled. Pts will be followed as in use in clinical practice. RAI-R pts will be evaluated. An equal number of RAI-S pts, matched for histology, age, sex and tumor stage will be analyzed. Genes, CSC, EMT and immunity profiles as well as biomarkers will be compared in RAI-R and RAI-S. The project will consist of: - Task 1: Genetic and molecular profiling of RAI-R and RAI-S DTC. Exome sequencing will be performed. Gene expression profile will be investigated. Focus on genes involved in EMT or in CSC biology will be posed to explore their role in RAI-R. CD133+ cells will be isolated and implanted in mice for further analysis. Annexin V and CD133-PE staining will be performed. - Task 2: Biomarkers profiling of RAI-R and RAI-S DTC. miRNA and proteins will be tested as serum biomarkers. Images will be analyzed (radiomics and/or machine/deep learning approaches) to test their prognostic role. - Task 3: RAI-R organoids. Tissue samples will be used to develop RAI-R DTC organoids that will be used to evaluate the mechanisms involved in RAI-R and to test drugs that may restore RAI sensitivity. Expected results and potential impact: Diverse molecular and genetic profiles as well as different biomarkers between RAI-R and RAI-S are expected. The identification of reliable biomarkers will impact on high risk DTC pts management and treatment potentially improving quality of life of pts and healthcare costs. |
| Network | TRANSCAN-2 |
| Call | 4th Joint Transnational Call (JTC 2017) |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | Istituto Clinico Humanitas (ICH) IRCCS | Coordinator | Italy |
| 2 | Philipps-University Marburg (UMR) | Partner | Germany |
| 3 | Azienda Unit̀ Sanitaria Locale di Reggio Emilia-IRCCS (AUSL-IRCCS) | Partner | Italy |
| 4 | National Yang-Ming University (NYMU) | Partner | Taiwan |