Several biomarkers have been suggested to have prognostic value in differentiated thyroid carcinomas (DTC) with no validation in the refractory setting, including all tumor subtypes. We aim to 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 the secondary 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% confidence interval (CI), 0.17–0.60; P < 0.001 and HR: 0.36 (95% CI, 0.21–0.63); 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 analysis for 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.

中文翻译：

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从决策试验中鉴定定义放射性碘难治性分化型甲状腺癌不同预后亚群的表达谱

一些生物标志物已被建议在分化型甲状腺癌 (DTC) 中具有预后价值，但在难治性环境中未经验证，包括所有肿瘤亚型。我们的目标是根据 DECISION 试验中包括的患者将 RNA 表达谱与生存相关联。我们从 DECISION 研究中包含的 417 名患者中获取了 247 个样本，并进行了 RNAseq 分析（HiSeq2000 上每个样本的 7700 万双末端读数）。质量控制后，125 个样本被纳入二次分析，并使用 ENCODE 参数通过 STAR (v2.5.1b) 映射到人类参考基因组 (GRCh38)。使用 Kaplan-Meier 方法计算生存分析，并使用对数秩检验进行统计比较。在此事后分析中，我们根据基因表达谱确定了三组肿瘤：BRAF 样、RAS 样和非 BRAF 非 RAS 样 (NoBRaL)。未观察到与索拉非尼反应者的显着相关性。然而，我们发现 RNA 表达谱与无进展生存之间存在统计学上显着的相关性。与 RAS 样和 NoBRaL 相比，BRAF 样特征具有明显更好的结果（分别为 11.8、6.2 和 5.5 个月）[HR：0.31，95% 置信区间 (CI)，0.17-0.60；P < 0.001 和 HR：0.36（95% CI，0.21–0.63）；P < 0.001] 和 HR：0.36（95% CI，0.21–0.63；P < 0.001）并且在甲状腺乳头状癌的多变量分析中作为总生存期的独立预后因素保持显着性。据我们所知，这是第一次对 DTC 的所有组织学亚型进行全面的 RNA-seq 分析。