Dados do Resumo

Título

A nutrição na identificação de biomarcadores no Câncer gástrico

Introdução

The FTO gene (Fat Mass and Obesity-associated) plays a critical role in tumorigenesis through epigenetic regulation, specifically through its function as a demethylase of RNA and DNA. FTO removes methyl groups from nucleotides, particularly the N6-methyladenosine (m6A) modification on RNA and 5-methylcytosine (5mC) on DNA, altering the expression of key genes involved in cell proliferation, apoptosis, and metabolism. In gastric adenocarcinoma tumorigenesis, FTO’s demethylation activity can deregulate the expression of critical genes such as MYC, PI3K, and AKT, which are central to cell growth and survival signaling cascades. FTO-mediated demethylation can increase the stability of oncogene mRNAs, enhancing their translation and amplifying proliferative signals. Additionally, FTO may influence the expression of tumor suppressor genes, such as PTEN, leading to the activation of pro-tumor pathways, such as the PI3K/AKT/mTOR pathway.

Objetivo

identify nutritional biomarkers present in gastric cancer that are potentially useful in the diagnosis and prognosis of gastric cancer

Métodos

The study included 43 patients with intestinal subtype gastric cancer and 21 with diffuse subtype, alongside 20 non-tumor samples for RNA sequencing (RNA-seq). Approved by the Research Ethics Committee (CAAE 47580121.9.0000.5634), RNA-seq was performed on the NextSeq®️ platform using the NextSeq®️ 500 MID Output V2 kit. Initial processing involved demultiplexing, quality filtering with Fastp (v0.23.2), and taxonomic classification using Kraken 2 (v2.1.3). Alignment was conducted with Salmon and Gencode version 43. Differential expression analysis was performed with DESeq2, using |Log2(Fold-Change)| > 1 and adjusted p-value < 0.05. ROC and discriminant analysis of principal components (DAPC) were utilized. Gene Set Enrichment Analysis (GSEA) with Reactome sets was conducted using the Fgsea package. A literature review identified 6 genes associated with metabolism, nutrition, and cancer, analyzed using KEGG pathways and gene ontology (GO) to elucidate the roles of these target proteins and mRNAs.

Resultados

A literature review and expression analysis identified six genes related to nutrition and metabolism as potential biomarkers in gastric adenocarcinoma, with only FTO previously reported as a possible biomarker. FTO was differentially expressed among groups (Kruskal-Wallis chi-squared = GC/ADJ 0.001, GC/MP, and ADJ/MP > 0.0000), showing the highest expression in adjacent tissues. FTO showed no correlation with PI3KCA/AKT but had an inverse correlation with MAP4K4. In this population, FTO expression alone did not impact survival probability.

Conclusões

Based on the analysis presented, FTO was identified as a differentially expressed gene in gastric adenocarcinoma, highlighting its potential as a biomarker, especially due to its increased expression in tissues adjacent to the tumor. Although FTO showed no correlation with the PI3K/AKT pathways, its inverse relationship with MAP4K4 suggests complex regulation in gastric tumorigenesis. However, isolated FTO expression did not significantly impact patient survival, highlighting the need to explore its interaction with other factors and molecular pathways more deeply to establish its prognostic role in gastric adenocarcinoma.

Palavras Chave

FTO; Transcriptome; RNA-seq