Distinct molecular subtypes of papillary thyroid carcinoma and gene signature with diagnostic capability

• DOI: 10.1038/s41388-022-02499-0
• Publication Date: 2022-10-17T14:09:41Z
• Authors: Shubin Hong; Yubin Xie; Zhen Cheng; Jie Li; Weiman He; Zhuming Guo; Quan Zhang; Sui Peng; Minghui He; Shuang Yu; Lixia Xu; Rengyun Liu; Tianyi Xu; Yunjian Zhang; Yanbing Li; Jiguang Wang; Weiming Lv; Jun Yu; Haipeng Xiao
• Keywords: Subtyping

Abstract Papillary thyroid carcinoma (PTC) is heterogeneous and its molecular characteristics remain elusive. We integrated transcriptomic sequencing, genomic analysis clinicopathologic information from 582 tissue samples of 216 PTC 75 benign nodule (BTN) patients. discovered four subtypes including Immune-enriched Subtype, BRAF-enriched Stromal Subtype CNV-enriched Subtype. Molecular were validated in an external cohort 497 cases the TCGA. Tumors showed higher immune infiltration overexpression checkpoints, whilst a tendency for extrathyroidal extension more advanced TNM stage. Key oncogenes LRRK2, SLC34A2, MUC1, FOXQ1 KRT19 overexpressed enriched oncogenic MAPK PI3K/AKT signaling pathways subtype. Further identified three subclasses with different degrees malignancies. also uncovered link initiation progression BTN to using trajectory analysis. Moreover, 20-gene expression signature was generated differential diagnosis Together, our work previously unreported PTC, offering opportunities stratify patients into optimal treatment plans based on subtyping.