PURPOSE: Heterogeneous ribonucleoprotein K (hnRNP K) regulates thymidine phosphorylase (TP) mRNA stability. The aim of the present study was to analyze hnRNP K and TP expression in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic and therapeutic potential of these two markers. EXPERIMENTAL DESIGN: We analyzed hnRNP K and TP expression immunohistochemically in 121 clinically proven NPC cases. Statistical analyses were applied to correlate cytoplasmic hnRNP K with elevated TP expression and determine the prognostic significance of these parameters. The therapeutic implication of elevated TP expression was determined by measuring sensitivity of NPC cells to the TP-targeting drug, 5-fluoro-5'-deoxyuridine (5'-DFUR). RESULTS: There was a high correlation between cytoplasmic hnRNP K and high TP (P < 0.001). Both cytoplasmic hnRNP K and high TP were associated with poor overall survival (OS; P = 0.007 and P < 0.001, respectively) and distant metastasis-free survival (P = 0.003 and 0.001, respectively) of NPC patients. A multivariate analysis confirmed that both cytoplasmic hnRNP K and high TP are independent prognostic predictors for OS (P = 0.020 and 0.010, respectively). NPC cells expressing high TP were more sensitive to treatment with the TP-targeting drug, 5'-DFUR. CONCLUSIONS: Cytoplasmic hnRNP K and high TP are associated with shorter OS and distant metastasis-free survival in NPC patients. In vitro experiments suggest that NPC tumors with high TP expression may be sensitive to 5'-DFUR treatment. Cytoplasmic hnRNP K and high TP may be potential prognostic and therapeutic markers for NPC, but additional validation studies are warranted.
PURPOSE: Heterogeneous ribonucleoprotein K (hnRNP K) regulates thymidine phosphorylase (TP) mRNA stability. The aim of the present study was to analyze hnRNP K and TP expression in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic and therapeutic potential of these two markers. EXPERIMENTAL DESIGN: We analyzed hnRNP K and TP expression immunohistochemically in 121 clinically proven NPC cases. Statistical analyses were applied to correlate cytoplasmic hnRNP K with elevated TP expression and determine the prognostic significance of these parameters. The therapeutic implication of elevated TP expression was determined by measuring sensitivity of NPC cells to the TP-targeting drug, 5-fluoro-5'-deoxyuridine (5'-DFUR). RESULTS: There was a high correlation between cytoplasmic hnRNP K and high TP (P < 0.001). Both cytoplasmic hnRNP K and high TP were associated with poor overall survival (OS; P = 0.007 and P < 0.001, respectively) and distant metastasis-free survival (P = 0.003 and 0.001, respectively) of NPC patients. A multivariate analysis confirmed that both cytoplasmic hnRNP K and high TP are independent prognostic predictors for OS (P = 0.020 and 0.010, respectively). NPC cells expressing high TP were more sensitive to treatment with the TP-targeting drug, 5'-DFUR. CONCLUSIONS: Cytoplasmic hnRNP K and high TP are associated with shorter OS and distant metastasis-free survival in NPC patients. In vitro experiments suggest that NPC tumors with high TP expression may be sensitive to 5'-DFUR treatment. Cytoplasmic hnRNP K and high TP may be potential prognostic and therapeutic markers for NPC, but additional validation studies are warranted.
Authors: Ali Fendri; Christos K Kontos; Abdelmajid Khabir; Raja Mokdad-Gargouri; Andreas Scorilas Journal: Mol Med Date: 2010-12-08 Impact factor: 6.354
Authors: Francesco Ricci; Alessandra Rubagotti; Linda Zinoli; Rosa Mangerini; Pier Vitale Nuzzo; Giorgio Carmignani; Alchiede Simonato; Paola Barboro; Cecilia Balbi; Francesco Boccardo Journal: J Cancer Res Clin Oncol Date: 2012-04-10 Impact factor: 4.553
Authors: Michal Mikula; Pawel Gaj; Karolina Dzwonek; Tymon Rubel; Jakub Karczmarski; Agnieszka Paziewska; Artur Dzwonek; Piotr Bragoszewski; Michal Dadlez; Jerzy Ostrowski Journal: DNA Res Date: 2010-06-29 Impact factor: 4.458
Authors: Robert van Domselaar; Razi Quadir; Astrid M van der Made; Roel Broekhuizen; Niels Bovenschen Journal: J Biol Chem Date: 2012-05-11 Impact factor: 5.157
Authors: P Barboro; E Repaci; A Rubagotti; S Salvi; S Boccardo; B Spina; M Truini; C Introini; P Puppo; N Ferrari; G Carmignani; F Boccardo; C Balbi Journal: Br J Cancer Date: 2009-04-28 Impact factor: 7.640