Dados do Trabalho

Título

MDM2 EXPRESSION AND HELICOBACTER PYLORI INFECTION EVIDENCE AN INVERSE RELATIONSHIP IN CARCINOGENESIS IN PATIENTS WITH GASTRIC ADENOCARCINOMA

Introdução

MDM2 is considered an essential negative regulator of p53. According to the literature, this gene may be associated with the susceptibility and pathogenesis of several types of cancer, including gastric cancer (GC), in which Helicobacter pylori infection also plays a role in the carcinogenesis process and seems to be related to the expression of specific genes. Therefore, possible associations may contribute to clinical management in GC. However, more studies are needed to elucidate better the mechanisms involved.

Objetivo

Thus, the objective of this study was to analyze and compare the expression profile of the MDM2 gene in samples from patients with GC and adjacent tissues in the state of Pará to associate this profile with the infection H. pylori with the stages of the GC (I, II, III, and IV) and the histological subtypes (intestinal and diffuse).

Métodos

We analyzed paired tumor and adjacent tissue samples from 42 patients (CAAE: 47580121.9.0000.5634). Total RNA was extracted using TRIzol® and evaluated for integrity using the 2200 TapeStation System (Agilent Technologies). RNA-seq was performed on the NextSeq® platform (Illumina®, USA). The readings were converted to FASTQ format using the Reporter software and mapped using the Salmon tool on the hg38 genome version of GENCODE. We used the DESeq2 package to analyze differential gene expression, with genes exhibiting expression variation [Log2(Fold-Change)] higher than two and p < 0.05 considered differentially expressed (DEG). We then associated the DEGs with clinicopathological data to evaluate their predictive value in the CG.

Resultados

An increase in MDM2 expression was observed in gastric cancer samples, with a statistically significant difference (p = 0.007) compared to non-neoplastic tissues. When associated with Helicobacter pylori infection, it was found that MDM2 is more expressed in patients who are negative for infection when compared to positive ones, with a statistically significant difference (p = 0.020). Regarding the association with gastric cancer stages (I, II, III, and IV), a lower expression of the gene was observed in stage I than in stages II, III, and IV (p = 0.043) and when compared with the subtypes histologically (intestinal to diffuse) there was no statistically significant difference (p = 0.130).

Conclusões

Given the results found, the expression of the MDM2 gene seems to have a direct relationship with gastric carcinogenesis and an inverse relationship with H. pylori infection. However, more research is needed to estimate its potential as a biomarker in gastric cancer.

Palavras-chave

Gastric cancer; MDM2; Helicobacter pylori.

Financiador do resumo

UFPA, CAPES, CNPq.

Área

Estudo Clínico - Tumores do Aparelho Digestivo Alto