Characterization of Human Endogenous Retroviruses in Gastric Cancer with Helicobacter pylori: A Study from Northern Brazil

Abstract

Human endogenous retroviruses (HERVs) are retroelements that have integrated their genetic material into the human genome, accumulating mutations over time and accounting for approximately 8% of the genome. Under abnormal deregulation conditions, these elements can be expressed and contribute to the development of diseases, such as gastric cancer. This malignancy may be associated with infections, including those caused by Helicobacter pylori. However, the scientific literature does not yet provide clear evidence regarding the relationship between HERVs and H. pylori in the context of gastric cancer. Thus, HERVs may represent potential biomarkers for this neoplasm, as well as possible therapeutic targets. This study aimed to characterize HERV expression in gastric cancer using next-generation sequencing (NGS). We analyzed 46 tumor tissue samples and 42 peritumoral tissue samples from patients diagnosed with gastric adenocarcinoma, collected at HUJBB and Ophir Loyola hospitals. Among the tumor samples, 38 tested positive for H. pylori infection. For library preparation, 1 g of total RNA per sample was used, with integrity assessed via TapeStation ([~]260 bp band). cDNA libraries were sequenced using the Illumina NextSeq 500 platform (paired-end), following the ID Output V2 kit protocol. Alignment was performed with STAR software, and HERVs were identified and quantified using Telescope. Differential expression analysis of HERVs was performed on transcript data using DESeq2. A total of 183 HERVs were found to be differentially expressed in tumor tissues compared to adjacent tissues. In tumor samples associated with H. pylori infection, 44 HERVs showed differential expression. Overall, tumor tissues exhibited higher HERV transcription compared to adjacent tissues.