title: Targeted Proteomics Predicts a Sustained Complete-Response after Transarterial Chemoembolization and Clinical Outcomes in Patients with Hepatocellular Carcinoma: A Prospective Cohort Study.
abstract: This study was aimed to identify blood-based biomarkers to predict a sustained complete response (CR) after transarterial chemoembolization (TACE) using targeted proteomics. Consecutive patients with HCC who had undergone TACE were prospectively enrolled (training (n = 100) and validation set (n = 80)). Serum samples were obtained before and 6 months after TACE. Treatment responses were evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). In the training set, the MRM-MS assay identified five marker candidate proteins (LRG1, APCS, BCHE, C7, and FCN3). When this five-marker panel was combined with the best-performing clinical variables (tumor number, baseline PIVKA, and baseline AFP), the resulting ensemble model had the highest area under the receiver operating curve (AUROC) value in predicting a sustained CR after TACE in the training and validation sets (0.881 and 0.813, respectively). Furthermore, the ensemble model was an independent predictor of rapid progression (hazard ratio (HR), 2.889; 95% confidence interval (CI), 1.612-5.178; P value < 0.001) and overall an unfavorable survival rate (HR, 1.985; 95% CI, 1.024-3.848; P value = 0.042) in the entire population by multivariate analysis. Targeted proteomics-based ensemble model can predict clinical outcomes after TACE. Therefore, this model can aid in determining the best candidates for TACE and the need for adjuvant therapy.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Su Jong
authors.initials: SJ
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Hyunsoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Hophil
authors.initials: H
authors.lastname: Min
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Sohn
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Young Youn
authors.initials: YY
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Jeong-Ju
authors.initials: JJ
authors.lastname: Yoo
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Dong Hyeon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Jungsoo
authors.initials: J
authors.lastname: Gim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Taesung
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Chung Yong
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine and Liver Research Institute, ‡Department of Biomedical Engineering, and §Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine , Yongon-Dong, Seoul 110-799, Korea.|Interdisciplinary Program in Bioinformatics and ⊥Department of Statistics, Seoul National University , Daehak-dong, Seoul 151-742, Korea.
authors.forename: Youngsoo
authors.identifier: 0000-0001-8881-0662
authors.initials: Y
authors.lastname: Kim
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000401:mortality / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D015331:Cohort Studies; D006801:Humans; D011379:Prognosis; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods*; D000069553:Supervised Machine Learning; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: HCC; TACE; multiple reaction monitoring-mass spectrometry (MRM-MS); prognostic biomarker; proteomics