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Heterogeneous Ribonucleoprotein K and Thymidine Phosphorylase Are Independent Prognostic and Therapeutic Markers for Nasopharyngeal Carcinoma

Authors' Affiliations: ¹ Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan; ² Chang Gung Molecular Medicine Research Center and ³ Graduate Institute of Basic Medical Sciences, Chang Gung University; Departments of ⁴ Pathology, ⁵ Radiation Oncology, and ⁶ Otolaryngology, Chang Gung Memorial Hospital at Lin-Kou, Taoyuan, Taiwan

Requests for reprints: Yu-Sun Chang, Graduate Institute of Basic Medical Sciences, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-shan, Taoyuan, Taiwan 333. Phone: 886-3-211-8683; Fax: 886-3-211-8683; E-mail: ysc{at}mail.cgu.edu.tw or ch9211{at}cgmh.org.tw.

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.