Dados do Trabalho

Título

Evaluation of cancer/testis antigens in patients diagnosed with gastric cancer in Pará.

Introdução

Gastric cancer is an aggressive malignant neoplasm with a heterogeneous character and is an obstacle to global health. Most diagnoses are late, which is why it is necessary to identify diagnostic and prognostic biomarkers for better therapeutic targeting. Cancer/testicular antigens (CTAs) are auto-antigens with restricted expression in the human germline, testis and in malignant tumors, making them possible tumor biomarkers and therapeutic targets. However, analysis of the tissue expression pattern of CTAs in gastric cancer patients remains poorly explored.However, analysis of the pattern of tissue expression of CTAs in patients with gastric cancer remains largely unexplored.

Objetivo

The aim of this study was to analyze the expression of CTAs in patients with gastric adenocarcinoma in the state of Pará.

Métodos

Paired samples of tumor and non-tumor tissue adjacent to the tumor (ADJ) were collected from 42 patients (CAAE:47580121.9.0000.5634) for total RNA sequencing. Based on the readings obtained, differential gene expression analysis was carried out using the DESeq2 package, in which CTAs that showed a difference in expression |Log2(Fold-Change)| greater than 1 and a p-value of less than 0.05 were assigned as differentially expressed (DE). To elucidate the biological roles of DE genes, gene ontology was performed. In addition, the impact of CTA expression on overall survival (OS) was evaluated.

Resultados

In total, 1894 DE genes were identified among tumor and ADJ samples, among which 57 genes belonging to the CTAs family. Among these, the genes DNAJB8 (LFC: -3.98); SSX5(LFC: -3.96) and SSX3(LFC:-3.63) were down-regulated, while POTEE (LFC: 2.85), IL13RA2 (LFC: 2.3) and IGHG1 (LFC: 1.57) were up-regulated.In addition, according to the clinic, the CCDC62, SSX3, SPAG6 and ADAM29 genes have a higher level of expression (p<0.05) when patients have positive Helicobacter pylori and the CCDCC110, POTEA, PRAME and FOSL1 genes have high expression (p<0.05) in EBV-negative patients. In addition, the expression of genes was analyzed according to the histological subtype of GC; in the intestinal subtype, the PBK and BCAP31 genes (p<0.05) were highly expressed and the ADAM29, RHOXF2, NOL4, and EPPIN genes (p<0.05) were more highly expressed in the diffuse subtype. In another evaluation of the CTAs, 16 appear to impact patients' OS, high levels of expression of VENTXP1 (p:0.00086), CCDC110 (p: 0.014), TDRD6 (p:0.025) and low expression of OTOA (p:0.0082), ADAM29 (p:0.0046) and IHO1 (p:0.019) are associated with unfavorable OS outcomes. DE CTAs were enriched 29 terms of biological processes, which are, cellular process involved in reproduction in multicellular organisms, germ cell development and meiotic cell cycle.

Conclusões

The present study highlights the functional relevance of CTAs for GC, however additional validations are needed to better understand the immunogenicity of CTAs and potential clinical translation.

Palavras-chave

cancer/testis antigens; gastric cancer ;biomarker

Financiador do resumo

Fundação Amazonia de Amparo a Estudos e Pesquisa(convênio 004/2021) and Coordenação de Aperfeiçoamento de nível Superior

Área

Estudo Clínico - Tumores do Aparelho Digestivo Alto