Evaluation of serum DNA integrity as a screening and prognostic tool in patients with hepatitis C virus-related hepatocellular carcinoma.

BACKGROUND

Hepatocellular carcinoma (HCC) is a common malignancy in Egypt due to the high frequency of hepatitis C virus (HCV) infection among the general population. Circulating free DNA is a potential molecular marker for the diagnosis and prognosis of malignant tumors. DNA released from apoptotic cells usually consists of short uniform fragments while DNA released from cancer cells is longer. The ratio of long DNA fragments to total DNA (DNA integrity) may be a potential marker for early detection of HCC and its progression in HCV patients.

METHODS

Sera from 25 patients with HCV-related HCC, 25 patients with chronic HCV infection, and 15 healthy volunteers were examined for Alu repeats by quantitative real-time PCR (qPCR) using 2 sets of primers of 115 and 247 base pairs. DNA integrity was calculated as the ratio of 247-bp to 115-bp Alu fragments.

RESULTS

Compared with healthy volunteers and HCV patients, significantly higher DNA integrity was found in HCC patients. DNA integrity was associated with tumor size, TNM stage, vascular invasion, lymph node involvement, and distant metastasis. DNA integrity had a higher sensitivity and specificity in discriminating HCC from HCV patients than total DNA. Patients with high DNA integrity had a significantly shorter overall survival and high DNA integrity was shown to be an independent prognostic factor for survival in HCV-related HCC.

CONCLUSIONS

DNA integrity is a promising molecular biomarker for detecting HCC in patients with chronic HCV infection; it reflects the progression and metastatic potential of the tumor, and high DNA integrity is associated with short overall survival in HCV-related HCC.