RASSF1A methylation as a biomarker for detection of colorectal cancer and hepatocellular carcinoma.

BACKGROUND

Studies have validated the potential of methylated cell-free DNA as a biomarker in various tumors, and methylated DNA in plasma may be a potential biomarker for cancer.

AIM

To evaluate the diagnostic value of RASSF1A methylation in plasma for colorectal cancer (CRC) and hepatocellular carcinoma (HCC).

METHODS

A total of 92 CRC patients, 67 colorectal polyp (CRP) patients, 63 HCC patients, and 66 liver cirrhosis (LC) patients were enrolled. The plasma DNA was subjected to DNA extraction, double-strand DNA concentration determination, bisulfite conversion, purification, single-strand DNA concentration determination, and digital polymerase chain reaction (PCR) detection. The methylation rate was calculated. The diagnostic value was evaluated by the area under the curve (AUC).

RESULTS

The age and sex in the CRC and CRP groups and the HCC and LC groups were also matched. The DNA methylation rate of RASSF1A in plasma in the CRC group was 2.87 ± 1.80, and that in the CRP group was 1.50 ± 0.64. DNA methylation of RASSF1A in plasma showed a significant difference between the CRC and CRP groups. The AUC of RASSF1A methylation for discriminating the CRC and CRP groups was 0.82 (0.76-0.88). The AUCs of T1, T2, T3 and T4 CRC and CRP were 0.83 (0.72-0.95), 0.87 (0.78-0.95), 0.86 (0.77-0.95), and 0.75 (0.64-0.85), respectively. The DNA methylation rate of RASSF1A in plasma in the HCC group was 4.45 ± 2.93, and that in the LC group was 2.46 ± 2.07. DNA methylation of RASSF1A in plasma for the HCC and LC groups showed a significant difference. The AUC of RASSF1A methylation for discriminating the HCC and LC groups was 0.70 (0.60-0.79). The AUCs of T1, T2, T3 and T4 HCC and LC were 0.80 (0.61, 1.00), 0.74 (0.59-0.88), 0.60 (0.42-0.79), and 0.68 (0.53-0.82), respectively.

CONCLUSION

RASSF1A methylation in plasma detected by digital PCR may be a potential biomarker for CRC and HCC.