Dados do Resumo

Título

Impact of Differential Expression of the HER2 Gene in Gastric Cancer

Introdução

Gastric cancer (GC), the third leading cause of death globally, has adenocarcinoma as the most common type, accounting for 90% of cases. The identification of molecular biomarkers is essential to understand and treat the disease. In this perspective, the HER2 gene, which plays an important role in regulating cell proliferation, survival and adhesion, has its amplification associated with more aggressive and chemoresistant tumors, thus becoming a relevant target of investigations.

Objetivo

The study aims to evaluate the expression of the HER2 gene in gastric adenocarcinoma samples and investigate its relationship with disease progression, histological type, neoadjuvant therapy, H. pylori and Epstein–Barr Virus (EBV) infections and impact on patient survival.

Métodos

Tumor and adjacent non-tumor tissue samples from 44 patients diagnosed with gastric adenocarcinoma (CAAE: 47580121.9.0000.5634) were analyzed. HER2 gene expression was assessed by RNA-seq. Total RNA extraction was performed with TRIzol®, followed by library construction using the TruSeq Stranded Total RNA kit. Sequencing was performed on the NextSeq® platform, with bioinformatic analysis conducted by read mapping and transcript quantification using Salmon software. Differential expression was determined based on the Wilcoxon-Mann-Whitney test, considering criteria of adjusted p-value < 0.05 and |Log2(fold change)| > 2. For survival analysis, the Kaplan-Meier curve was used, with a statistically significant cutoff point.

Resultados

The results showed a significant increase in HER2 expression in tumor samples compared to adjacent non-tumor tissues (p-value: 0.00089). The data showed that HER2 expression is significantly higher in EBV-negative cases (p-value: 0.00379). However, no significant association was observed between HER2 expression and the presence of H. pylori infections (p-value: 0.35789), between the different stages of the disease (p-value: 0.07647) and with Lauren's histological subtypes (p-value: 0.20413). Regarding the use of neoadjuvant therapies, there was a trend towards reduced HER2 expression in patients who received neoadjuvant therapy, but the data are still inconclusive (p-value: 0.05355). Survival analysis demonstrated that patients with higher HER2 expression had lower overall survival (p-value: 0.0071).

Conclusões

The amplification of the HER2 gene in patients with gastric cancer associated with a lower survival rate reinforces the potential role of this gene as a prognostic biomarker, helping to define personalized therapeutic strategies, aiming to improve the survival of patients with GC. In addition, the greater expression of HER2 in cases of negative EBV suggests evaluating the status of this infection to guide the use of targeted therapies, since EBV-negative patients would possibly respond better to anti-HER2 treatments.

Financiador do resumo

National Council for Scientific and Technological Development

Palavras Chave

Gastric Adenocarcinoma; HER2; Gene Expression