CONTEXT Papillary Thyroid Microcarcinoma (PTMC) is the most common type of thyroid cancer. It had been approved that lymph node metastasis was associated with poor prognosis in PTMC patients. OBJECTIVE We aim to characterize Papillary Thyroid Microcarcinoma (PTMC) transcriptome landscape and identify the candidate transcripts that associated with lateral neck lymph node metastasis of PTMC. METHODS We performed full-length transcriptome sequencing in 64 PTMC samples. Standard bioinformatic pipelines were applied to characterize and annotate the full-length expression profiles of two PTMC subtypes. Functional ORF annotation of the known and novel transcripts were predicted by HMMER, DeepLoc, and DeepTMHMM tools. Candidate transcripts associated with pN1b subtype were identified after transcript quantification and differential gene expression analyses. RESULTS We found that skipping exon (SE) accounted for the more than 27.82% of the alternative splicing events. At least 42.56% of the discovered transcripts were novel isoforms of annotated genes. A total of 39,193 ORFs in novel transcripts and 18,596 ORFs in known transcripts were identified. Distribution patterns of the characterized transcripts in functional domain, subcellular localization, and transmembrane structure were predicted. Totally 1,033 and 1,204 differentially expressed genes were identified in pN0 and pN1b groups, respectively. Moreover, novel isoforms of FRMD3, NOD1, and SHROOM4 were highlighted for their association with pN1b subtype. CONCLUSION Our data provided the global transcriptome landscape of PTMC and also revealed the novel isoforms that associated with PTMC aggressiveness.

中文翻译：

---

全面的长读长测序分析揭示了甲状腺微小乳头状癌的转录组特征。

背景 甲状腺微小乳头状癌 (PTMC) 是最常见的甲状腺癌类型。现已证实淋巴结转移与 PTMC 患者预后不良有关。目的 我们的目的是描述甲状腺微小乳头状癌 (PTMC) 转录组格局，并鉴定与 PTMC 颈侧淋巴结转移相关的候选转录本。方法 我们对 64 个 PTMC 样本进行了全长转录组测序。应用标准生物信息学流程来表征和注释两种 PTMC 亚型的全长表达谱。通过 HMMER、DeepLo​​c 和 DeepTMHMM 工具预测已知和新转录本的功能 ORF 注释。经过转录本定量和差异基因表达分析后，鉴定了与 pN1b 亚型相关的候选转录本。结果我们发现跳跃外显子（SE）占可变剪接事件的27.82%以上。至少 42.56% 的已发现转录本是注释基因的新亚型。共鉴定出新转录本中的 39,193 个 ORF 和已知转录本中的 18,596 个 ORF。预测了特征转录本在功能域、亚细胞定位和跨膜结构中的分布模式。pN0组和pN1b组分别鉴定出1,033个和1,204个差异表达基因。此外，FRMD3、NOD1 和 SHROOM4 的新亚型因其与 pN1b 亚型的关联而受到关注。结论我们的数据提供了 PTMC 的全球转录组图谱，并揭示了与 PTMC 攻击性相关的新亚型。