乳头状甲状腺微小癌（PTMC）的发病率显著增加，部分病例仍然表现出侵袭性特征。目前，PTMC的整个分子景观（可以为癌症的病因提供线索）仍然缺乏。我们通过分析64名PTMC患者的全外显子组测序和RNA测序数据的最大研究，将我们的发现与TCGA中的PTMC发现进行了比较。然后，我们基于多组学分析系统地证明了两种PTMC亚型之间的差异。此外，我们创建了一种PTMC亚型的分子预测模型，并在TCGA患者中验证了它们，以进行个性化综合评估。除了TCGA队列中的BRAF突变和RET融合之外，我们还发现了一种名为PTMC-炎性的新的分子签名，它意味着潜在的免疫干预反应，其中包括AFP突变、IGH@-ext融合、免疫相关基因升高、过氧化物酶抗体阳性和甲状腺球蛋白抗体阳性。此外，我们创建了一种PTMC-炎性患者的分子预测模型，并在TCGA患者中进行了验证，而这些患者的预后较差。我们的发现全面定义了PTMC的临床和分子特征，并可能启发新的治疗假设。©2023。作者（们）。

Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent.We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the current stage of whole exome sequencing and RNA-sequencing data from 64 patients with PTMC. Then, we systematically demonstrated the differences between the two PTMC subtypes based on multi-omics analyses. Additionally, we created a molecular prediction model for the PTMC subtypes and validated them among TCGA patients for individualized integrative assessment.In addition to the presence of BRAF mutations and RET fusions in the TCGA cohort, we also discovered a new molecular signature named PTMC-inflammatory that implies a potential response to immune intervention, which is enriched with AFP mutations, IGH@-ext fusions, elevated immune-related genes, positive peroxidase antibody, and positive thyroglobulin antibody. Additionally, a molecular prediction model for the PTMC-inflammatory patients was created and validated among TCGA patients, while the prognosis for these patients is poor.Our findings comprehensively define the clinical and molecular features of PTMC and may inspire new therapeutic hypotheses.© 2023. The Author(s).