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Mucinous and non-mucinous colorectal cancers show differential expression of chemotherapy metabolism and resistance genes.
O'Connell, E; Reynolds, I S; Salvucci, M; McNamara, D A; Burke, J P; Prehn, J H M.
Afiliación
  • O'Connell E; Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
  • Reynolds IS; Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
  • Salvucci M; Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
  • McNamara DA; Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
  • Burke JP; Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
  • Prehn JHM; Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
Pharmacogenomics J ; 21(4): 510-519, 2021 08.
Article en En | MEDLINE | ID: mdl-33731881
Previous research has identified differences in mutation frequency in genes implicated in chemotherapy resistance between mucinous and non-mucinous colorectal cancers (CRC). We hypothesized that outcomes in mucinous and non-mucinous CRC may be influenced by expression of genes responsible for chemotherapy resistance. Gene expression data from primary tumor samples were extracted from The Cancer Genome Atlas PanCancer Atlas. The distribution of clinical, pathological, and gene expression variables was compared between 74 mucinous and 521 non-mucinous CRCs. Predictors of overall survival (OS) were assessed in a multivariate analysis. Kaplan-Meier curves were constructed to compare survival according to gene expression using the log rank test. The median expression of 5-FU-related genes TYMS, TYMP, and DYPD was significantly higher in mucinous CRC compared to non-mucinous CRC (p < 0.001, p = 0.003, p < 0.001, respectively). The median expression of oxaliplatin-related genes ATP7B and SRPK1 was significantly reduced in mucinous versus non-mucinous CRC (p = 0.004, p = 0.007, respectively). At multivariate analysis, age (odds ratio (OR) = 0.96, p < 0.001), node positive disease (OR = 0.49, p = 0.005), and metastatic disease (OR = 0.32, p < 0.001) remained significant negative predictors of OS, while high SRPK1 remained a significant positive predictor of OS (OR = 1.59, p = 0.037). Subgroup analysis of rectal cancers demonstrated high SRPK1 expression was associated with significantly longer OS compared to low SRPK1 expression (p = 0.011). This study highlights that the molecular differences in mucinous CRC and non-mucinous CRC extend to chemotherapy resistance gene expression. SRPK1 gene expression was associated with OS, with a prognostic role identified in rectal cancers.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inactivación Metabólica / Neoplasias Colorrectales / Resistencia a Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male Idioma: En Revista: Pharmacogenomics J Asunto de la revista: BIOLOGIA MOLECULAR / FARMACOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Irlanda Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inactivación Metabólica / Neoplasias Colorrectales / Resistencia a Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male Idioma: En Revista: Pharmacogenomics J Asunto de la revista: BIOLOGIA MOLECULAR / FARMACOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Irlanda Pais de publicación: Estados Unidos