RESUMEN

BACKGROUND AND OBJECTIVES: DNA repair is a new and important pathway that explains colorectal carcinogenesis. This study will evaluate the prognostic value of molecular modulation of double-strand break repair (XRCC2 and XRCC5); DNA damage tolerance/translesion synthesis (POLH, POLK, and POLQ), and interstrand crosslink repair (DCLRE1A) in sporadic colorectal cancer (CRC). METHODS: Tumor specimens and matched healthy mucosal tissues from 47 patients with CRC who underwent surgery were assessed for gene expression of XRCC2, XRCC5, POLH, POLK, POLQ, and DCLRE1A; protein expression of Polk, Ku80, p53, Ki67, and mismatch repair MLH1 and MSH2 components; CpG island promoter methylation of XRCC5, POLH, POLK, POLQ, and DCLRE1A was performed. RESULTS: Neoplastic tissues exhibited induction of POLK (P < .001) and DCLRE1A (P < .001) expression and low expression of POLH (P < .001) and POLQ (P < .001) in comparison to healthy paired mucosa. Low expression of POLH was associated with mucinous histology and T1-T2 tumors (P = .038); low tumor expression of POLK was associated with distant metastases (P = .042). CRC harboring POLK promoter methylation exhibited better disease-free survival (DFS) (P = .005). CONCLUSIONS: This study demonstrated that low expression or unmethylated POLH and POLK were related to worse biological behavior tumors. However, POLK methylation was associated with better DFS. POLK and POLH are potential prognostic biomarkers in CRC.

Asunto(s)

Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Roturas del ADN de Doble Cadena , Reparación del ADN , Anciano , Biomarcadores/metabolismo , Estudios de Casos y Controles , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorrectales/metabolismo , Islas de CpG , Daño del ADN , Metilación de ADN , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , ADN Polimerasa Dirigida por ADN/genética , ADN Polimerasa Dirigida por ADN/metabolismo , Supervivencia sin Enfermedad , Exodesoxirribonucleasas/genética , Exodesoxirribonucleasas/metabolismo , Femenino , Expresión Génica , Humanos , Autoantígeno Ku/genética , Autoantígeno Ku/metabolismo , Masculino , Homólogo 1 de la Proteína MutL/genética , Homólogo 1 de la Proteína MutL/metabolismo , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Metástasis de la Neoplasia/genética , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , ADN Polimerasa theta