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Persistent Aberrations in Circulating DNA Integrity after Radiotherapy Are Associated with Poor Prognosis in Nasopharyngeal Carcinoma Patients

Authors' Affiliations: ¹ State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Departments of ² Chemical Pathology and ³ Clinical Oncology, and ⁴ Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region, China

Requests for reprints: Y.M. Dennis Lo, Department of Chemical Pathology, Room 38023, 1/F, Clinical Science Building, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong Special Administrative Region, China. Phone: 852-2632-2963; Fax: 852-2636-5090; E-mail: loym@cuhk.edu.hk.

Purpose: Aberrations of circulating nucleic acid integrity have been observed in cancer patients. However, the clinical significance of such changes has not been completely elucidated. In this study, we investigated the plasma DNA integrity in nasopharyngeal carcinoma (NPC) patients and its association with patients' survival after radiotherapy.

Experimental Design: Plasma DNA integrity was analyzed for 105 NPC patients before and after curative-intent radiotherapy and for 40 healthy controls. The plasma DNA concentration of each sample was measured by two real-time PCRs targeting the leptin gene. The amplicon sizes of the two assays were 105 and 201 bp. The integrity index was calculated as the ratio of the two concentrations (201 bp/105 bp). More intact circulating DNA would give a higher integrity index.

Results: The plasma DNA integrity index of the NPC patients was significantly higher than that of the healthy controls (median, 0.356 versus 0.238; P < 0.001). After radiotherapy, a reduction in plasma DNA integrity index was observed in 70% NPC patients. Patients with persistent aberrations of plasma DNA integrity had significantly poorer survival probability than those with reduced DNA integrity after treatment (P < 0.001, Kaplan-Meier).

Conclusions: NPC is associated with disturbances in the integrity of circulating cell-free DNA. The persistence of DNA integrity aberrations after radiotherapy is associated with reduced probability of disease-free survival. Therefore, the measurement of plasma DNA integrity may serve as a useful marker for the detection and monitoring of malignant diseases.