Comprehensive long-read sequencing analysis discloses the transcriptome features of Papillary Thyroid Microcarcinoma

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.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.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.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.Our data provided the global transcriptome landscape of PTMC and also revealed the novel isoforms that associated with PTMC aggressiveness.