Heterogeneous ribonucleoprotein K and thymidine phosphorylase are independent prognostic and therapeutic markers for nasopharyngeal carcinoma

Purpose: Heterogeneous ribonucleoprotein K(hnRNP K) regulates thymidine phosphorylase (TP) mRNA stability. The aim of the present study was to analyze RNP 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 elevatedTP expression and determine the prognostic significance of these parameters. The therapeutic implication of elevatedTP expression was determined by measuring sensitivity of NPC cells to theTP-targiting 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=0.0007 and P<0.001, respectively) and distant metastasis-free survival (P=0.003 and 0.001, respectivtively) 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 highTP were more sensitive to treatment with theTP-targeting drug, 5'-DFUR. Conclusion: Cytoplasmic hnRNP K and highTP are associated with shorter OS and destant metastasis-free survival in NPC patients In vitro experiments suggest that NPC tumors with highTP expression may be sensitive to 2'-DFUR treatment. Cytoplasmic hnRNP K and highTP may be potential prognostic and therapeutic markers for NPC, but additional validation studies are warranted.