HLA-restricted Epitopes Prediction of Papillary Thyroid Carcinoma

Background The development of next-generation sequencing(NGS) technology such as transcriptome sequencing(RNA-seq) and the development of computer science have made the research on gene mutation or gene fusion that can produce new antigens more and more efficient and accurate. To identify immunogenic HLA-restricted epitopes of papillary thyroid carcinoma (PTC), we analyzed differential expression genes (DEGs) obtained by transcriptome sequencing. Methods The paired tumor samples and peritumoral thyroid tissue samples from 10 PTC patients were obtained for RNA extraction, library construction, and RNA-seq. DEGs were analyzed to identify genetic variants and fusion genes. Human leukocyte antigen (HLA) I genotype was determined by PCR-seqence specific primers(SSP) test and the analysis of RNA-seq data by HLAprofiler. The single nucleotide variations (SNVs), insertion/deletion mutations (INDELs) and fusion genes results from RNA-seq were coupled with HLA I allele to predict the possible antigen epitopes using the netMHCpan of pVACtools software. Results For 10 pair samples performing RNA-seq, as the differential expression criterion was |log2FoldChange|≥1 and Padj ≤ 0.05, there were 3740 DEGs between tumor samples and peritumoral thyroid tissue samples totally. Among them, compared to peritumoral thyroid tissue samples, 1464 genes were up-regulated and 2276 genes were down-regulated in tumor samples. Epitopes LAHPGFFYF (P4HA1), KTYERLFYM (PHLDB3), and LLYSNGYNY (IGKV2(D)-28) were predicted and filtered by genetic variation data coupled with HLA I allele. Epitopes KSAELSPFL (KSR1-LGALS9) and RASCQLTVL (FARSA-SYCE2) were predicted and filtered by fusion genes data. Conclusions RNA-seq results indicated that genetic alteration driving PTC progression also results in immunogenic HLA-restricted epitopes, which could be affect the immunogenicity of PTC and provide a new target for PTC treatment.