Heterogeneous ribonucleoprotein k and thymidine phosphorylase are independent prognostic and therapeutic markers for nasopharyngeal carcinoma.
OBJECTIVE
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.


METHODS
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.
Chen
Lih-Chyang
LC
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
Hsueh
Chuen
C
Tsang
Ngan-Ming
NM
Liang
Ying
Y
Chang
Kai-Ping
KP
Hao
Sheng-Po
SP
Yu
Jau-Song
JS
Chang
Yu-Sun
YS
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor / Q000378:metabolism / Q000502:physiology*; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D003593:Cytoplasm / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005467:Floxuridine / Q000627:therapeutic use; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000378:metabolism / Q000502:physiology*
D000964:Antimetabolites, Antineoplastic; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D005467:Floxuridine; D013939:Thymidine Phosphorylase; C025034:doxifluridine