Upregulation of human endogenous retrovirus-K (HML-2) mRNAs in hepatoblastoma: Identification of potential new immunotherapeutic targets and biomarkers

AbstractPurpose Hepatoblastoma is the most common liver malignancy in children. In order to advance therapy against hepatoblastoma, novel immunologic targets and biomarkers are needed. Our purpose this investigation examine hepatoblastoma transcriptomes for expression of a class genomic elements known as Human Endogenous Retrovirus (HERVs). HERVs abundant human genome biologically active that have been associated with multiple malignancies proposed subset tumors. A sub-family HERVs, HERV-K(HML-2) (HERV-K), shown be tightly regulated fetal development, making these pediatric tumors paramount. Methods We first created HERVK-FASTA file utilizing 91 previously described HML-2 proviruses. then concatenated onto GRCh38.95 cDNA library from Ensembl. used reference database evaluate existing RNA-seq data 10 3 normal controls (GEO accession ID: GSE8977575). Quantification differential proviral analysis between was performed using pseudo-alignment program Salmon DESeq2, respectively. Results HERV-K mRNA expressed loci. All loci were upregulated compared controls. Five proviruses (1q21.3, 3q27.2, 7q22.2, 12q24.33 17p13.1) significantly differentially (p-adjusted value <0.05, |log2 fold change| > 1.5) across conditions. The provirus at 17p13.1 had an approximately 300-fold increased liver. This part due near absence locus fully differentiated samples. Conclusions demonstrates several results suggest may useful biomarker given large profiles very low levels control