title: MAPK7 and MAP2K4 as prognostic markers in osteosarcoma.
abstract: Osteosarcoma is a class of cancer originating from the bone, affecting mainly children and young adults. Cytogenetic studies showed the presence of rearrangements and recurrent gains in specific chromosomal regions, indicating the possible involvement of genes located in these regions during the pathogenesis of osteosarcoma. These studies investigated expression of 10 genes located in the chromosomal region involved in abnormalities in osteosarcoma, 1p36, 17p, and chromosome 19. The purpose of this study was to investigate the expression profile of genes located in regions involved in chromosomal rearrangements in osteosarcoma. We used quantitative real-time polymerase chain reaction to investigate the expression of 10 genes located in 1p36.3 (MTHFR, ERRFI1, FGR, E2F2), 17p (MAPK7, MAP2K4), and chromosome 19 (BBC3, FOSB, JUND, and RRAS), in 70 samples taken from 30 patients (30 prechemotherapy, 30 postchemotherapy, and 10 metastases specimens) and 10 healthy bones as a control sample. The most interesting results showed a strong association between the expression levels of MAPK7 and MAP2K4 genes and clinical parameters of osteosarcoma. Overexpression of these genes was significantly associated to a poor response to treatment (P = .0001 and P = .0049, respectively), tumor progression, and worse overall survival (P = .0052 and P = .0085, respectively), suggesting that MAPK7 and MAP2K4 could play an important role in osteosarcoma tumorigenesis. Thus, these genes could be good markers in assessing response to treatment and development of osteosarcoma.
authors.affiliation: Department of Pediatrics, Pediatric Oncology Institute (Grupo de Apoio ao Adolescente e à Criança com Câncer), Federal University of São Paulo, São Paulo, SP 04023-062, Brazil. francine.tesser@yahoo.com.br
authors.forename: Francine
authors.initials: F
authors.lastname: Tesser-Gamba
authors.forename: Antonio Sergio
authors.initials: AS
authors.lastname: Petrilli
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: de Seixas Alves
authors.forename: Reynaldo Jesus Garcia
authors.initials: RJ
authors.lastname: Filho
authors.forename: Yara
authors.initials: Y
authors.lastname: Juliano
authors.forename: Sílvia Regina Caminada
authors.initials: SR
authors.lastname: Toledo
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002648:Child; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics*; D008297:Male; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics*; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D048054:Mitogen-Activated Protein Kinase 7; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human