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DNA Methylation Biomarkers as Prediction Tools for Therapeutic Response and Prognosis in Intermediate-Stage Hepatocellular Carcinoma.


ABSTRACT:

Introduction

Alfa-fetoprotein (AFP), as the main serum tumor marker of hepatocellular carcinoma (HCC), is limited in terms of specificity and ability to predict outcomes. This study investigated the clinical utility of DNA methylation biomarkers to predict therapeutic responses and prognosis in intermediate-stage HCC.

Methods

This study enrolled 72 patients with intermediate-stage HCC who underwent locoregional therapy (LRT) between 2020 and 2021. The immediate therapeutic response and disease status during a two-year follow-up were recorded. Analysis was performed on 10 selected DNA methylation biomarkers via pyrosequencing analysis of plasma collected before and after LRT.

Results

Analysis was performed on 53 patients with complete responses and 19 patients with disease progression after LRT. The mean follow-up duration was 2.4 ± 0.6 years. A methylation prediction model for tumor response (MMTR) and a methylation prediction model for early progression (MMEP) were constructed. The area under the curve (AUC) for sensitivity and specificity of MMTR was 0.79 for complete response and 0.759 for overall survival. The corresponding AUCs for sensitivity and specificity of AFP and protein induced by vitamin K absence-II (PIVKA-II) were 0.717 and 0.708, respectively. Note that the MMTR index was the only significant predictor in multivariate analysis. The AUC for sensitivity and specificity of the MMEP in predicting early progression was 0.79. The corresponding AUCs for sensitivity and specificity of AFP and PIVKA-II were 0.758 and 0.714, respectively. Multivariate analysis revealed that platelet count, beyond up-to-7 criteria, and the MMEP index were strongly correlated with early tumor progression. Combining the indexes and serum markers further improved the predictive accuracy (AUC = 0.922). Multivariate analysis revealed the MMEP index was the only independent risk factor for overall survival.

Discussion/conclusions

This study indicates that these methylation markers could potentially outperform current serum markers in terms of accuracy and reliability in assessing treatment response and predicting outcomes. Combining methylation markers and serum markers further improved predictive accuracy, indicating that a multi-marker approach may be more effective in clinical practice. These findings suggest that DNA methylation biomarkers may be a useful tool for managing intermediate-stage HCC patients and guiding personalized treatment, particularly for those who are at high risk for close surveillance or adjuvant treatment after LRT.

SUBMITTER: Lu CY 

PROVIDER: S-EPMC10527266 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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DNA Methylation Biomarkers as Prediction Tools for Therapeutic Response and Prognosis in Intermediate-Stage Hepatocellular Carcinoma.

Lu Chang-Yi CY   Hsiao Chih-Yang CY   Peng Pey-Jey PJ   Huang Shao-Chang SC   Chuang Meng-Rong MR   Su Hung-Ju HJ   Huang Kai-Wen KW  

Cancers 20230907 18


<h4>Introduction</h4>Alfa-fetoprotein (AFP), as the main serum tumor marker of hepatocellular carcinoma (HCC), is limited in terms of specificity and ability to predict outcomes. This study investigated the clinical utility of DNA methylation biomarkers to predict therapeutic responses and prognosis in intermediate-stage HCC.<h4>Methods</h4>This study enrolled 72 patients with intermediate-stage HCC who underwent locoregional therapy (LRT) between 2020 and 2021. The immediate therapeutic respons  ...[more]

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