Profiling radioREsistant Differentiated thyroid Cancer: genes, immunity, cancer stem cells and epithelial-mesenchymal transition
Martina Sollini (Italy), Istituto Clinico Humanitas (ICH) IRCCS, Department of Diagnostic Imaging, Rozzano (Milan)
Markus Luster (Germany), Philipps-University Marburg (UMR), Nuclear Medicine Department, Marburg
Ciarrocchi Alessia (Italy), Azienda Unit. Sanitaria Locale di Reggio Emilia-IRCCS (AUSL-IRCCS), Scientific Direction - Lab. of Translational Research, Reggio Emilia
Oscar K. Lee (Taiwan), National Yang-Ming University (NYMU), Stem Cell Research Center, Taipei
Background and rationale: 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.
- 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.
(Project funded under JTC 2017)