Dados do Resumo

Título

ANALYSIS OF MELK EXPRESSION IN GASTRIC CANCER PATIENTS AT A UNIVERSITY HOSPITAL IN PARÁ, BRAZIL.

Introdução

Gastric cancer is the fifth most common tumor and the fourth leading cause of cancer-related death worldwide. Its mechanisms are still not fully understood, and specific biomarkers and therapeutic targets are lacking, resulting in a poor prognosis. MELK kinase, a member of the AMP-related serine-threonine kinase family, plays a role in tumorigenesis, cancer cell proliferation, tumor resistance and cell cycle regulation, and is also associated with stem cell renewal and chemotherapy resistance.

Objetivo

Investigate MELK expression in tumor fragments samples of gastric cancer patients to evaluate the correlations between MELK gene expression and different clinical data, including tumor origin, Lauren's classification and tumor topography.

Métodos

This study collected 124 samples of gastric cancer, 62 adjacent tissue and 20 metaplastic tissue from patients at Hospital Universitário João de Barros Barreto (HUJBB), from Federal University of Pará (UFPA). All participants were informed about the objectives and provided consent via an Informed Consent Form (ICF). The study was approved by the HUJBB Ethics Committee (CAAE 47580121.9.0000.5634). Tumor tissue samples were preserved in RNA later and stored at -80°C. Clinical data from patients, including tumor origin, Lauren’s classification, and tumor topography, were collected. Total RNA was extracted, assessed for integrity and used to construct cDNA libraries, which were sequenced on the Illumina NextSeq system. Quality reads were processed and aligned to the human transcriptome, and gene expression levels were estimated using the DESeq2 package in R software. Statistical analyses included Wilcoxon, Kruskal-Wallis and Benjamini-Hochberg tests, with p < 0.05 significant.

Resultados

The data show that the GC and adjacent tissue groups have significantly higher MELK expression compared to metaplastic tissue (p= 0.0004; p= 0.005, respectively), but there was no statistical significance between GC and adjacent tissue (p= 0.11). In relation to the Lauren classification, MELK was more expressed in the intestinal subtype, compared to the diffuse and mixed subtypes, but without statistical significance (p= 0.47352). In terms of tumor topography, MELK expression was higher in the Body-Antrum junction region compared to the Body, Antrum and Cardia separately (p= 0.0025; p= 0.0022; p=0.02), with no statistical difference in relation to the Fundus (p=0.07).

Conclusões

MELK is differentially expressed in gastric cancer and adjacent tissues compared to metaplastic samples. Furthermore, MELK is overexpressed in the antrum-body junction, suggesting that this gene may favor tumor progression in this region. Our findings indicate the potential of MELK as a biomarker and therapeutic target in gastric cancer. However, further studies are needed to confirm our hypothesis, even with a larger sample population.

Palavras Chave

biomarkers; gastric cancer; MELK