ETV4 plays a role on the primary events during the adenoma-adenocarcinoma progression in colorectal cancer

Author(s):Show less -

Fonseca, Aline Simoneti ^{[1, 2, 3, 4, 5]} ; Ramao, Anelisa ^{[1, 2, 3]} ; Buerger, Matheus Carvalho ^{[1, 2]} ; Santana de Souza, Jorge Estefano ^{[1, 2]} ; Zanette, Dalila Luciola ^{[1, 2, 3, 4, 6]} ; de Molfetta, Greice Andreotti ^{[1, 2, 3, 4]} ; de Araujo, Luiza Ferreira ^{[1, 2, 3, 4]} ; Bueno, Rafaela de Barros e Lima ^{[1, 2, 3]} ; Aguiar, Graziela Moura ^{[1, 2]} ; Placa, Jessica Rodrigues ^{[1, 2]} ; Alves, Cleidson de Padua ^{[1, 2]} ; Dinarte dos Santos, Anemari Ramos ^[1] ; Vidal, Daniel Onofre ^{[1, 2]} ; Barros Silva, Gyl Eanes ^[7] ; Panepucci, Rodrigo Alexandre ^{[1, 2]} ; Peria, Fernanda Maris ^[8] ; Feres, Omar ^[9] ; Ribeiro da Rocha, Jose Joaquim ^[9] ; Zago, Marco Antonio ^{[1, 2]} ; Silva, Jr., Wilson Araujo ^{[1, 2, 3, 4]}

Affiliation

^[1] Natl Inst Sci & Technol Stem Cell & Cell Therapy, Ribeirao Preto, SP - Brazil

^[2] Ctr Cell Based Therapy, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] NAP USP, Ctr Integrat Syst Biol CISBi, Ribeirao Preto, SP - Brazil

^[5] Res Inst Pele Pequeno Principe, Av Silva Jardim 1632, BR-80250060 Curitiba, PR - Brazil

^[6] Fundacao Oswaldo Cruz, Inst Carlos Chagas, Lab Appl Sci & Technol Hlth LASTH, Curitiba, PR - Brazil

^[7] Presidente Dutra Univ Hosp HUUFMA, Lab Immunofluorescence & Electron Microscopy LIME, Sao Luis, MA - Brazil

^[8] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Med Clin, USP, Ribeirao Preto, SP - Brazil

^[9] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Surg & Anat, Sao Paulo - Brazil

• Document type: Journal article
• Source: BMC CANCER; v. 21, n. 1 MAR 1 2021.
• Web of Science Citations: 0

Abstract

BackgroundColorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause of death in the world and the third in Brazil. Mutations in the APC, DCC, KRAS and TP53 genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition.MethodsTen paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene expression analysis. In addition, mutations in APC, KRAS and TP53 genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients.ResultsGene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change>2, p<0.05), between the adenoma and adenocarcinoma paired samples analyzed. Gene pathway analysis using the 689 DEG identified important cancer pathways such as remodeling of the extracellular matrix and epithelial-mesenchymal transition. Among these DEG, the ETV4 stood out as one of the most expressed in the adenocarcinoma samples, further confirmed in the adenocarcinoma set of samples from the TCGA database. Subsequent in vitro siRNA assays against ETV4 resulted in the decrease of cell proliferation, colony formation and cell migration in the HT29 and SW480 colorectal cell lines. DNA sequencing analysis revealed KRAS and TP53 gene pathogenic mutations, exclusively in the adenocarcinomas samples.ConclusionOur study identified a set of genes with high potential to be used as biomarkers in CRC, with a special emphasis on the ETV4 gene, which demonstrated involvement in proliferation and migration. (AU)

• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC