1.Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won KIM ; Jin Hyun PARK ; Suk Kyun HONG ; Min-Hyeok JUNG ; Ji-One PYEON ; Jin-Young LEE ; Kyung-Suk SUH ; Nam-Joon YI ; YoungRok CHOI ; Kwang-Woong LEE ; Young-Joon KIM
Clinical and Molecular Hepatology 2025;31(2):563-576
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods:
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results:
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
2.Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won KIM ; Jin Hyun PARK ; Suk Kyun HONG ; Min-Hyeok JUNG ; Ji-One PYEON ; Jin-Young LEE ; Kyung-Suk SUH ; Nam-Joon YI ; YoungRok CHOI ; Kwang-Woong LEE ; Young-Joon KIM
Clinical and Molecular Hepatology 2025;31(2):563-576
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods:
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results:
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
3.Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won KIM ; Jin Hyun PARK ; Suk Kyun HONG ; Min-Hyeok JUNG ; Ji-One PYEON ; Jin-Young LEE ; Kyung-Suk SUH ; Nam-Joon YI ; YoungRok CHOI ; Kwang-Woong LEE ; Young-Joon KIM
Clinical and Molecular Hepatology 2025;31(2):563-576
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods:
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results:
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
4.A Machine Learning Model for Prostate Cancer Prediction in Korean Men
Sukjung CHOI ; Beomgi SO ; Shane OH ; Hongzoo PARK ; Sang Wook LEE ; Geehyun SONG ; Jong Min LEE ; Jung Ki JO ; Seon Hyeok KIM ; Si Eun LEE ; Eun-Bi CHO ; Jae Hung JUNG ; Jeong Hyun KIM
Journal of Urologic Oncology 2024;22(3):201-210
Purpose:
Unnecessary prostate biopsies for detecting prostate cancer (PCa) should be minimized. Therefore, this study developed a machine learning (ML) model to predict PCa in Korean men and evaluated its usability.
Materials and Methods:
We retrospectively analyzed clinical data from 928 patients who underwent prostate biopsies at Kangwon National University Hospital between May 2013 and May 2023. Of these, 377 (41.6%) were diagnosed with PCa, and 551 (59.4%) did not have cancer. For external validation, clinical data from 385 patients aged 48–89 years who underwent prostate biopsies from September 2005 to September 2023 at Wonju Severance Christian Hospital were also included. Twenty-two clinical features were used to develop an ML model to predict PCa. Features were selected based on their contributions to model performance, leading to the inclusion of 15 features. A meta-learner was constructed using logistic regression to predict the probability of PCa, and the classifier was trained and validated on randomly extracted training and test sets at an 8:2 ratio.
Results:
The prostate health index, prostate volume, age, nodule on digital rectal examination, and prostate-specific antigen were the top 5 features for predicting PCa. The area under the receiver operating characteristic curve (AUC) of the meta-learner logistic regression model was 0.89, and the accuracy, sensitivity, and specificity were 0.828, 0.711, and 0.909, respectively. Our model also showed excellent prediction performance for high-grade PCa, with a Gleason score of 7 or higher and an AUC of 0.903. Furthermore, we evaluated the performance of the model using external cohort clinical data and achieved an AUC of 0.863.
Conclusions
Our ML model excelled in predicting PCa, specifically clinically significant PCa. Although extensive cross-validation in other clinical cohorts is needed, this ML model is a promising option for future diagnostics.
5.Efficacy and safety evaluation of imidafenacin administered twice daily for continency recovery following radical prostatectomy in prostate cancer patients: Prospective open-label case-controlled randomized trial
Jun Hee LEE ; Hyeok Jun GOH ; Kisoo LEE ; Dong Won CHOI ; Kwang Min LEE ; Soodong KIM
Investigative and Clinical Urology 2024;65(5):466-472
Purpose:
This study aims to prospectively analyze the effects of anticholinergic therapy using imidafenacin on detrusor overactivity occurring after robot-assisted radical prostatectomy (RARP).
Materials and Methods:
Patients were followed-up at outpatient visits 2–4 weeks post-surgery (visit 2) to confirm the presence of urinary incontinence. Those confirmed with urinary incontinence were randomly assigned in a 1:1 ratio to the anticholinergic medication group (imidafenacin 0.1 mg twice daily) or the control group. Patients were followed-up at 1, 3, and 6 months post-surgery for observational assessments, including the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS).
Results:
A total of 49 patients (25 in the treatment group and 24 in the control group) were randomized for the study. There were no differences observed between the groups in terms of age, comorbidities, prostate size, or pathological staging. According to the IPSS questionnaire results, there was no statistically significant difference between the medication and control groups (p=0.161).However, when comparing storage and voiding symptoms separately, there was a statistically significant improvement in storage symptom scores (p=0.012). OABSS also revealed statistically significant improvement in symptoms from 3 months post-surgery (p=0.005), which persisted until 6 months post-surgery (IPSS storage: p=0.023, OABSS: p=0.013).
Conclusions
In the case of urinary incontinence that occurs after RARP, even if the function of the intrinsic sphincter is sufficiently preserved, if urinary incontinence persists due to changes in the bladder, pharmacological therapy using imidafenacin can be beneficial in managing urinary incontinence.
6.A Machine Learning Model for Prostate Cancer Prediction in Korean Men
Sukjung CHOI ; Beomgi SO ; Shane OH ; Hongzoo PARK ; Sang Wook LEE ; Geehyun SONG ; Jong Min LEE ; Jung Ki JO ; Seon Hyeok KIM ; Si Eun LEE ; Eun-Bi CHO ; Jae Hung JUNG ; Jeong Hyun KIM
Journal of Urologic Oncology 2024;22(3):201-210
Purpose:
Unnecessary prostate biopsies for detecting prostate cancer (PCa) should be minimized. Therefore, this study developed a machine learning (ML) model to predict PCa in Korean men and evaluated its usability.
Materials and Methods:
We retrospectively analyzed clinical data from 928 patients who underwent prostate biopsies at Kangwon National University Hospital between May 2013 and May 2023. Of these, 377 (41.6%) were diagnosed with PCa, and 551 (59.4%) did not have cancer. For external validation, clinical data from 385 patients aged 48–89 years who underwent prostate biopsies from September 2005 to September 2023 at Wonju Severance Christian Hospital were also included. Twenty-two clinical features were used to develop an ML model to predict PCa. Features were selected based on their contributions to model performance, leading to the inclusion of 15 features. A meta-learner was constructed using logistic regression to predict the probability of PCa, and the classifier was trained and validated on randomly extracted training and test sets at an 8:2 ratio.
Results:
The prostate health index, prostate volume, age, nodule on digital rectal examination, and prostate-specific antigen were the top 5 features for predicting PCa. The area under the receiver operating characteristic curve (AUC) of the meta-learner logistic regression model was 0.89, and the accuracy, sensitivity, and specificity were 0.828, 0.711, and 0.909, respectively. Our model also showed excellent prediction performance for high-grade PCa, with a Gleason score of 7 or higher and an AUC of 0.903. Furthermore, we evaluated the performance of the model using external cohort clinical data and achieved an AUC of 0.863.
Conclusions
Our ML model excelled in predicting PCa, specifically clinically significant PCa. Although extensive cross-validation in other clinical cohorts is needed, this ML model is a promising option for future diagnostics.
7.A Machine Learning Model for Prostate Cancer Prediction in Korean Men
Sukjung CHOI ; Beomgi SO ; Shane OH ; Hongzoo PARK ; Sang Wook LEE ; Geehyun SONG ; Jong Min LEE ; Jung Ki JO ; Seon Hyeok KIM ; Si Eun LEE ; Eun-Bi CHO ; Jae Hung JUNG ; Jeong Hyun KIM
Journal of Urologic Oncology 2024;22(3):201-210
Purpose:
Unnecessary prostate biopsies for detecting prostate cancer (PCa) should be minimized. Therefore, this study developed a machine learning (ML) model to predict PCa in Korean men and evaluated its usability.
Materials and Methods:
We retrospectively analyzed clinical data from 928 patients who underwent prostate biopsies at Kangwon National University Hospital between May 2013 and May 2023. Of these, 377 (41.6%) were diagnosed with PCa, and 551 (59.4%) did not have cancer. For external validation, clinical data from 385 patients aged 48–89 years who underwent prostate biopsies from September 2005 to September 2023 at Wonju Severance Christian Hospital were also included. Twenty-two clinical features were used to develop an ML model to predict PCa. Features were selected based on their contributions to model performance, leading to the inclusion of 15 features. A meta-learner was constructed using logistic regression to predict the probability of PCa, and the classifier was trained and validated on randomly extracted training and test sets at an 8:2 ratio.
Results:
The prostate health index, prostate volume, age, nodule on digital rectal examination, and prostate-specific antigen were the top 5 features for predicting PCa. The area under the receiver operating characteristic curve (AUC) of the meta-learner logistic regression model was 0.89, and the accuracy, sensitivity, and specificity were 0.828, 0.711, and 0.909, respectively. Our model also showed excellent prediction performance for high-grade PCa, with a Gleason score of 7 or higher and an AUC of 0.903. Furthermore, we evaluated the performance of the model using external cohort clinical data and achieved an AUC of 0.863.
Conclusions
Our ML model excelled in predicting PCa, specifically clinically significant PCa. Although extensive cross-validation in other clinical cohorts is needed, this ML model is a promising option for future diagnostics.
8.Comparison of High- and Low-Dose Rivaroxaban Regimens in Elderly East Asian Patients With Atrial Fibrillation
Ju Youn KIM ; Juwon KIM ; Seung-Jung PARK ; Kyoung-Min PARK ; June Soo KIM ; Sung-Hwan KIM ; Jaemin SHIM ; Eue Keun CHOI ; Dae-Hyeok KIM ; Il-Young OH ; Young Keun ON ;
Journal of Korean Medical Science 2024;39(8):e72-
Background:
In the Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban 20 mg was the on-label dose, and the dose-reduction criterion for rivaroxaban was a creatinine clearance of < 50 mL/min. Some Asian countries are using reduced doses label according to the J-ROCKET AF trial. The aim of this study was to assess the safety and efficacy of a high-dose rivaroxaban regimen (HDRR, 20/15 mg) and low-dose rivaroxaban regimen (LDRR, 15/10 mg) among elderly East Asian patients with atrial fibrillation (AF) in real-world practice.
Methods:
This study was a multicenter, prospective, non-interventional observational study designed to evaluate the efficacy and safety of rivaroxaban in AF patients > 65 years of age with or without renal impairment.
Results:
A total of 1,093 patients (mean age, 72.8 ± 5.8 years; 686 [62.9%] men) were included in the analysis, with 493 patients allocated to the HDRR group and 598 patients allocated to the LDRR group. A total of 765 patients received 15 mg of rivaroxaban (203 in the HDRR group and 562 in the LDRR group). There were no significant differences in the incidence rates of major bleeding (adjusted hazard ratio [HR], 0.64; 95% confidential interval [CI], 0.21–1.93), stroke (adjusted HR, 3.21; 95% CI, 0.54–19.03), and composite outcomes (adjusted HR, 1.13;95% CI, 0.47–2.69) between the HDRR and LDRR groups.
Conclusion
This study revealed the safety and effectiveness of either dose regimen of rivaroxaban in an Asian population for stroke prevention of AF. Considerable numbers of patients are receiving LDRR therapy in real-world practice in Asia. Both regimens were safe and effective for these patients.
9.Higher Fat-Related Body Composition Measurement and Lower Resting-State Inter-Network Functional Connectivity of APOE ε4 Carrier in Mild Cognitive Impairment Patients With Aβ Deposition
In Hyeok CHOI ; Sheng-Min WANG ; Yoo Hyun UM ; Hyun Kook LIM ; Chang Uk LEE ; Dong Woo KANG
Psychiatry Investigation 2023;20(12):1177-1184
Objective:
We aimed to evaluate the impact of interaction between APOE ε4 carrier status and body composition measurements on intra- and inter-regional functional connectivity (FC) in mild cognitive impairment (MCI) patients with Aβ deposition.
Methods:
MCI patients with and without APOE ε4 allele (carrier, n=86; non-carrier, n=95) underwent neuropsychological battery, resting-state functional magnetic resonance imaging scans, positron emission tomography scans with [18 F]flutemetamol, and bioelectrical impedance analysis for measuring body composition. We employed a priori defined regions of interest to investigate the intra- and inter-network FC profiles of default mode network (DMN), central executive network (CEN), and salience network.
Results:
There was a significant interaction of APOE ε4 carrier status with body fat mass index, visceral fat area, and waist-hip circumference ratio for inter-network FC between DMN and CEN, contributing higher fat-related body composition measurements in the APOE ε4 carrier with lower DMN-CEN FC.
Conclusion
The present results highlight the detrimental effect of APOE ε4 carrier status on the associations between the fat-related body composition measurements and FC in the MCI patients with Aβ accumulation.
10.Unequal burdens of COVID-19 infection: a nationwide cohort study of COVID-19-related health inequalities in Korea
Jeangeun JEON ; Jieun PARK ; Min-Hyeok CHOI ; Hongjo CHOI ; Myoung-Hee KIM
Epidemiology and Health 2023;45(1):e2023068-
OBJECTIVES:
While the Korean government’s response to the coronavirus disease 2019 (COVID-19) pandemic is considered effective given the relatively low mortality rate, issues of inequality have been insufficiently addressed. This study explored COVID-19-related health inequalities in Korea.
METHODS:
Age standardization for various health inequality indices was derived using data from the Korean National Health Insurance Service, the Korea Disease Control and Prevention Agency, and the Microdata Integrated Service of Statistics Korea. The slope index of inequality (SII) and relative index of inequality (RII) were calculated for socioeconomic variables, while absolute difference (AD) and relative difference (RD) were used for gender and disability inequalities.
RESULTS:
We observed a number of COVID-19-related health outcome inequalities. Gender inequality was particularly noticeable in infection rates, with the rate of women 1.16 times higher than that of men. In contrast, socioeconomic inequality was evident in vaccination rates, with a 4.5-fold (SII, -4.519; 95% confidence interval, -7.403 to -1.634) difference between the highest and lowest household income groups. Regarding clinical progression post-infection, consistent findings indicated higher risk for men (RD for hospitalization, 0.90; severe cases, 0.54; and fatality, 0.65), individuals with disabilities (RD for hospitalization, 2.27; severe cases, 2.29; and fatality, 2.37), and those from lower socioeconomic groups (SII for hospitalization, 1.778; severe cases, 0.089; and fatality, 0.451).
CONCLUSIONS
While the infection risk was nearly ubiquitous, not everyone faced the same level of risk post-infection. To prevent further health inequalities, it is crucial to develop a thoughtful policy acknowledging individual health conditions and resources.

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