Purpose: Recent research has shown the feasibility of detecting cell-free RNA markers in human subjects. As elevated RNase activity has previously been described in the circulation of cancer patients, we hypothesized that cancer patients may have reduced plasma RNA integrity. In this study, we used nasopharyngeal carcinoma (NPC) as a model system to test this hypothesis. Experimental Design: Plasma RNA integrity was determined using the ratio of the concentrations of transcript sequences corresponding to the 3V to those from the 5V end of a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Transcript concentrations were measured using real-time quantitative reverse transcription-PCR assays targeting the 5V and 3V regions. We analyzed the plasma RNA integrity in 49 untreated NPC patients and 53 healthy controls. We also assessed the plasma samples from 19 NPC patients before and after radiotherapy to further show the clinical potential of this marker. Results: The 3V to 5V GAPDH ratio was significantly lower in the plasma of untreated NPC patients when compared with healthy controls (0.0252 versus 0.0485, P = 0.024). Statistical analysis showed that plasma GAPDH ratio was correlated with tumor stage but not with sex and age. Moreover, 14 of 19 NPC patients (74%) showed significant increase in the plasma GAPDH ratio following radiotherapy (P = 0.003). All of these patients were in clinical remission after treatment. Conclusions: Our findings suggest that NPC is associated with disturbances in the integrity of cell-free circulating RNA, raising the possibility that measurement of plasma RNA integrity may serve as a useful marker for the diagnosis and monitoring of malignant diseases.Plasma RNA analysis has emerged as a potential tool in cancer detection and monitoring (1). The clinical implication of cellfree circulating RNA was first shown by two independent groups in 1999. Kopreski et al. (2) detected tyrosinase mRNA in the serum of patients suffering from malignant melanoma. Concurrently, Lo et al. (3) showed the presence of EBVencoded RNA in the plasma of nasopharyngeal carcinoma (NPC) patients. These findings have since prompted further investigation, linking circulating RNA with malignant diseases and opening up the possibility of finding new molecular tumor markers in blood. Moreover, the recent demonstration of the unexpected stability of circulating RNA has attested the practicality of this approach for future clinical use (4, 5).Apart from potential diagnostic significance, the study of plasma nucleic acids has also yielded data with biological significance, concerning particularly the molecular characteristics of such species. In the area of plasma DNA, our group has previously shown that most of the EBV DNA molecules detected in the plasma of cancer patients were <180 bp long (6), and that fetal DNA observed in the plasma of pregnant women was relatively shorter than the maternal counterparts (7). Beyond plasma DNA analysis, plasma RNA was found to exhibit another remarkabl...