Dados do Trabalho

Título

Analysis of the gene expression of TRPV calcium channels in gastric cancer

Introdução

Recent research has explored the TRPV family of channels in gastric cancer (GC). When expression of these channels in the plasma membrane is unregulated, an increase in the Ca2+ dependent proliferative response provides a survival advantage for tumor cells. As GC has an uneven worldwide distribution and not all information in the literature applies to all patients, new approaches that seek to understand the role of TRPVs in carcinogenesis are becoming more relevant.

Objetivo

To investigate the gene expression profile of the TRPV calcium channel family in gastric cancer samples in the state of Pará and evaluate its role in carcinogenesis.

Métodos

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

Expression analysis of TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6 genes indicate that in GC tumor tissue the TRPV3 (p=0.00026) and TRPV6 (p=5.6e-05) genes showed reduced expression concerning its adjacent tissues. In addition, H.pylori-positive test patients had increased expression of the TRPV3 gene compared to those who tested negative. Notably, we saw no significant impact on overall patient survival due to altered TRPV3 and TRPV6 gene expression, and neoadjuvant therapy did not affect the gene expression of TRPVs. Likewise, positive or negative samples for the Epstein-Barr virus did not affect the expression of these genes. There is a gap in the knowledge of TRPV3 and TRPV6 gene modulation in GC. Furthermore, the TRPV family of calcium channels influences the interactions between tumor cells and their gastric microenvironment, which may have tissue-specific particularities with differential actions not yet investigated.

Conclusões

Our research has shown that the expression of TRPV3 and TRPV6 is altered in gastric cancer patients. We have seen an increase in expression in the adjacent tissue, which suggests that these channels may be crucial in the disease progression. Although the TRPV family's role in gastric cancer is still debated, the varying expression of TRPV3 and TRPV6 indicates the involvement of a specific pathway in this tumor type. More research is necessary to comprehend the implications of these findings.

Palavras-chave

Gastric cancer; gene expression; TRPV family.

Financiador do resumo

UFPA, CAPES, CNPq

Área

Estudo Clínico - Tumores do Aparelho Digestivo Alto