The GALAD scoring algorithm based on AFP, AFP-L3, and DCP significantly improves detection of BCLC early stage hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of death in cirrhotic patients worldwide. The detection rate for early stage HCC remains low despite screening programs. Thus, the majority of HCC cases are detected at advanced tumor stages with limited treatment options. To facilitate earlier diagnosis, this study aims to validate the added benefit of the combination of AFP, the novel biomarkers AFP-L3, DCP, and an associated novel diagnostic algorithm called GALAD. Between 2007 and 2008 and from 2010 to 2012, 285 patients newly diagnosed with HCC and 402 control patients suffering from chronic liver disease were enrolled. AFP, AFP-L3, and DCP were measured using the µTASWako i30 automated immunoanalyzer. The diagnostic performance of biomarkers was measured as single parameters and in a logistic regression model. Furthermore, a diagnostic algorithm (GALAD) based on gender, age, and the biomarkers mentioned above was validated. AFP, AFP-L3, and DCP showed comparable sensitivities and specifities for HCC detection. The combination of all biomarkers had the highest sensitivity with decreased specificity. In contrast, utilization of the biomarker-based GALAD score resulted in a superior specificity of 93.3 % and sensitivity of 85.6 %. In the scenario of BCLC 0/A stage HCC, the GALAD algorithm provided the highest overall AUROC with 0.9242, which was superior to any other marker combination. We could demonstrate in our cohort the superior detection of early stage HCC with the combined use of the respective biomarkers and in particular GALAD even in AFP-negative tumors.

Serum Exosomal MicroRNA, miR-10b-5p, as a Potential Diagnostic Biomarker for Early-Stage Hepatocellular Carcinoma

“…Many previously reported studies on HCC serum biomarkers have proposed a combination of HCC-derived novel biomarker and serum AFP for improving diagnostic efficiency. Recently, AFP-L3 and des-γ-carboxy prothrombin (DCP) have been suggested as HCC biomarkers [12,13]. However, the reported AUC for AFP-L3 and DCP was found to be about 0.73 and 0.71, respectively.…”

Quantum biophysics of water

“…Much effort has recently focused on combinations of markers, such as AFP plus AFP-L3 plus DCP for use in surveillance [49]. Even in patients with very low AFP (<20 ng/ml), sensitivity was over 65% using these 3 marker combinations [50,51]. However, the different clinical HCC phenotypes for these marker combinations has not been explored in detail, except for the association of increased incidence of PVT in patients with high DCP levels [52].…”

Identification of Platform-Independent Diagnostic Biomarker Panel for Hepatocellular Carcinoma Using Large-Scale Transcriptomics Data

“…It is implemented using in-house R scripts after the assignment of samples to the respective class, i.e., cancer or normal. These tests have been applied previously in different studies for the identification of DEGs (WELCH, 1947;Akaiwa et al, 1999;Carvalho and Irizarry, 2010;Aino et al, 2014;Schulze et al, 2015;Best et al, 2016;Bhasin et al, 2016;Bhalla et al, 2017;Cai et al, 2017;Bhalla et al, 2019;Cai et al, 2019;Kaur et al, 2019). Wilcoxon T-test is used for paired samples and Welch T-test is used for unpaired samples.…”

“…The clinical characteristics of the patients like age, gender, tumor size, and stage are considered as important prognostic indicators for the survival of the patients in different malignancies including HCC (Best et al, 2016;Liu et al, 2018a;Wu et al, 2018;Yang et al, 2019). As the tumor size information is not present in one of the cohorts, therefore, we performed univariate survival analysis using only age, gender, and tumor stage of the patients.…”