PRJNA563018
Identification of expression profiles defining distinct prognostic subsets of radioactive-iodine refractory differentiated thyroid cancer from the decision trial
Several biomarkers have been suggested to have prognostic value in differentiated thyroid cancer (DTC) with no validation in refractory setting including all tumor subtypes.We aimto correlate RNA expression profiles with survival based on patients included in the DECISION trial. We obtained 247 samples from the 417 patients included in the DECISION study and performed RNAseq analysis (77 million paired-end reads for each sample on HiSeq2000). After quality control, 125 samples were included in thesecondary analysis and mapped against the human reference genome (GRCh38) with STAR (v2.5.1b) using ENCODE parameter. Survival analysis was calculated using the Kaplan–Meier method and log-rank test was used for statistical comparison. In this post-hoc analysis we identified three groups of tumors based on their gene expression profile: BRAF-like, RAS-like, and non-BRAF-non-RAS-like (NoBRaL). No significant correlation with sorafenib responders was observed. However, we identified a statistically significant correlation between the RNA-expression profiles and progression-free survival. The BRAF-like profile had a significantly better outcome compared with RAS-like and NoBRaL (11.8,6.2 and 5.5 months, respectively), HR: 0.31 (95% CI 0.17-0-60, p<0.001) and HR:0.36 (95% CI 0.21-0.63, p<0.001) and maintained significance as an independent prognostic factor for overall survival in the multivariate analysisfor papillary thyroid cancers. To our knowledge, this is the first comprehensive RNA-seq analysis of all histologic subtypes of DTC. The RNA expression profiles identified may suggest a new prognostic parameter to be considered before recommendation of systemic therapies or the design of stratification factors for future clinical trials.