Diagnostic and prognostic performance of PAK1 methylation in patients with hepatocellular carcinoma undergoing liver transplantation
- Author:
Shin HWANG
1
;
Hyo Jung KO
;
Eunyoung TAK
;
Kyoung-Jin LEE
;
Yun-Kyu LEE
Author Information
- Publication Type:Original Article
- From: Clinical Transplantation and Research 2026;40(1):104-115
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background:DNA methylation is under investigation as an early diagnostic biomarker for cancers such as hepatocellular carcinoma (HCC). p21-activated protein kinase 1 (PAK1) demonstrates a high methylation tendency in HCC. We assessed the diagnostic and prognostic performance of PAK1 methylation in liver transplantation (LT) recipients with and without HCC.
Methods:To assess PAK1 methylation, stored pretransplant blood samples from LT recipients were analyzed by droplet digital polymerase chain reaction.
Results:This study included 274 patients with HCC and 100 control patients without the disease. Ten-year survival rates in the HCC and control groups were 60.5% and 80.6%, respectively (P=0.001). The 10-year HCC recurrence rate was 39.0%. Ten-year survival rates in the HCC recurrence and nonrecurrence groups were 13.3% and 91.2%, respectively (P<0.001); median PAK1 methylation levels in the control and HCC groups were 50.0 and 108.0 copies (P=0.102). The area under the receiver operating characteristic curve was 0.599, and the Youden J index was 0.199, indicating 57.9% sensitivity and 62.0% specificity at a cutoff of 78 copies. With a cutoff of 5 copies, sensitivity was 94.1% and specificity was 14.0%. The positive likelihood ratio was 1.09 and the negative likelihood ratio was 0.42, indicating diagnostic accuracy below α-fetoprotein and protein induced by vitamin K absence or antagonist-II. PAK1 cutoffs of 5 and 10 copies did not affect HCC recurrence, but a cutoff of 2 copies appeared associated with lower recurrence.
Conclusions:These data suggest that PAK1 methylation is not a clinically useful biomarker for HCC in LT recipients. New DNA methylation biomarkers are required for early diagnosis.
