Dados do Resumo

Título

Analysis of the expression of human endogenous retroviruses associated with Helicobacter pylori in gastric cancer

Introdução

Human endogenous retroviruses (HERVs) are retroelements from exogenous viruses that make up 8% of the human genome. When activated by infections, they can cause diseases such as gastric cancer (GC). It is estimated that 50% of adults worldwide are infected with Helicobacter pylori, and although only 1% develop GC, it is the main cause of the tumor. The role of HERVs in pathogen-associated cancer is still unclear, but they may be important biomarkers for H. pylori-related GC.

Objetivo

This study aims to understand the expression profile of HERVs in gastric cancer associated with H. pylori infection.

Métodos

This study, approved by the Research Ethics Committee of Barros Barreto Hospital (HUJJB/UFPA), under CAAE number 47580121.9.0000.5634, included 45 GC samples and 41 adjacent region (ADJ) samples from patients with gastric adenocarcinoma from HUJJB and Ophir Loyola (HOL) hospitals. Total RNA was extracted with TRIzol® and analyzed for concentration and integrity. Libraries were constructed with the TruSeq Standard Total RNA kit and sequenced in pair-end mode on the NextSeq® platform. Reads were analyzed with FastQC and Trimmomatic, followed by alignment with STAR and quantification of HERVs with Telescope. Differential expression (GC vs ADJ) was analyzed in RStudio with the DESeq2 package, considering HERVs with Log2(Fold-Change) > 2 and p-adj < 0.05. Transcripts with AUC > 0.7 were filtered with the pROC package. ANOVA and Tukey’s test (p-adj < 0.001) were used for statistical analysis.

Resultados

We found 27 underexpressed and 215 overexpressed transcripts. Through AUC, we identified 7 differentially expressed HERVs: ERV-LE, HERV-30, HERV-H, HERV-L, HERV-P71A, HERV-W, and MER4-B. All the HERVs showed elevated expression in the region adjacent to the gastric tumor. When comparing between H. pylori-infected and non-infected individuals, expression among the positively tested was higher than among the negatively tested. Through analysis according to tissue type, infection, and HERVs, H. pylori-positive cases showed prominence for HERV-H_2q32.1e and MER4-B_1q43a, while H. pylori-negative cases showed prominence for HERV30_8q24.32 and HERVP71A_4q28.3, with greater significance between ADJ and GC.

Conclusões

Our data suggest that differentially expressed HERVs may be associated with H. pylori infection, especially in ADJ, with the potential to contribute to the development of gastric cancer. However, further studies are needed to understand the functions of HERVs in the gastric tumor microenvironment.

Financiador do resumo

Fundação Amazônia de Amparo a Estudos e Pesquisas (FAPESPA) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Palavras Chave

Human endogenous retroviruses; gastric cancer; Helicobacter pylori