Dados do Trabalho

Título

IMPACT OF DEREGULATION OF RTEL1 GENE EXPRESSION ON GASTRIC CARCINOGENESIS

Introdução

Identifying new biomarkers in diagnosing or prognostic evaluating gastric cancer (GC) has become an indispensable tool in understanding this neoplasia. In light of this, previous studies conducted by our research group have demonstrated different potential biomarkers, including the RTEL1 gene (encoding the telomerase enzyme), which showed recurrent amplifications in GC samples, necessitating further investigations to elucidate its role in GC better.

Objetivo

Thus, we aimed to analyze and compare the expression profile of the RTEL1 gene in samples from patients with GC in the state of Pará and adjacent tumor tissues, associate this profile with histological subtype and overall survival, and correlate the expression of RTEL1 with that of other genes involved in GC.

Métodos

We analyzed paired tumor tissue samples and adjacent (non-tumor) 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

We observed increased RTEL1 expression in GC samples, with a statistically significant difference (p=0.004) in expression between GC and adjacent tissues. When associating with histological subtypes, we found that RTEL1 is more expressed in the intestinal type, although there was no statistically significant difference. However, previous results demonstrated by our research group mentioned that 38% of the samples presented amplification, more associated with the intestinal type (ARAÚJO et al., 2016). Regarding association with overall survival, we found that patients with increased RTEL1 gene expression experienced a reduction in survival rate compared to those with lower expression (p=0.013). When correlating the expression profile of RTEL1 with other genes involved in gastric carcinogenesis, we identified a positive correlation with the genes NSMF, BNI1, SLC12A, and AGRN and a negative correlation with the genes CHST9, ADHFE1, CWH43, and TMEM108.

Conclusões

Given the addressed data, the RTEL1 gene becomes an exciting target in gastric carcinogenesis, presenting promising initial results. However, further studies are necessary to validate its potential as a biomarker in this neoplasia.

Palavras-chave

Gastric Cancer; RTEL1; Molecular biomarker; NGS.

Financiador do resumo

Federal University of Pará (UFPA), Coordination for the Improvement of Higher Education Personnel (CAPES), National Council for Scientific and Technological Development (CNPq).