The concentration of deoxyribonucleic acid in plasma from 73 patients with colorectal cancer and apparent clinical correlations

Abstract

Background: Detection of cell-free plasma DNA has considerable potential as a tool for the diagnosis and assessment of the prognosis of many types of cancer. The aim of the present study was to quantify, by spectrophotometry, the cell-free DNA in plasma samples from patients with colorectal cancer at different stages of the disease and to attempt to correlate the resultant values with the clinical picture. Methods: We reviewed the medical reports of 73 patients, who had undergone resection of primary colorectal cancer. Samples of blood had been taken from each patient immediately prior to surgery. DNA was extracted from samples of plasma and quantified, by spectrophotometry, after a storage period of no longer than 2 years in 89% of the cases examined. Results: The mean(±S.D.) concentration of DNA in plasma samples was 108 ± 156 ng/μl. We found a statistically significant correlation between the concentration of DNA and the presence of metastases (mainly liver metastases). Conclusion: The detection and quantitation of cell-free DNA in plasma, using this simple technique, might be of clinical value for the surveillance of colon cancer patients and the detection of metastases.

Introduction

The presence of high levels of cell-free DNA in plasma is not exclusive to cancer; it is also associated with, for example, infectious diseases (miliary tuberculosis and pyogenic abscess) [1], chronic inflammatory diseases (rheumatoid arthritis and systemic lupus erythematosus) [2], [3], tissue destruction (acute hepatitis, trauma and stroke), pregnancy, and treatment with high doses of corticoids [4].

There is a pressing need for clinical tools with which to make an early diagnosis and to detect the recurrence of tumors and to improve the monitoring of cancer patients. Many attempts have been made to develop routine laboratory tests [5] but, in colorectal cancer, for example, no definitive methods have been established [6], [7], [8], [9]. The quantitative techniques examined by different researchers include radioimmunoassay [10], [11], competitive PCR [11], [12], ELISA [11], [13], quantitative real-time PCR [8], [11], fluorometric quantitation [11], [14], and visual comparison with standards (DipStick Kits) [11], [15]. There is general agreement that, on average, levels of plasma DNA are elevated in cancer patients [5]. However, absolute amounts vary among studies, probably as a result of the different types of cancer studied and the great variety of techniques employed. Spectrophotometry has also been proved to be an useful tool for this for this purpose [11], [16], moreover, sophisticated and expensive procedures are normally not available in the clinical setting.

The aim of the present study was to quantify, by spectrophotometry, the cell-free DNA in plasma samples from patients with colorectal cancer at different stages of the disease and to attempt to correlate the resultant values with the clinical picture.