{
  "abstract": "Hepatocellular carcinoma surveillance relies on ultrasonography and alpha-fetoprotein, both limited in sensitivity for early-stage disease; aberrant methylation of circulating cell-free DNA (cfDNA) offers a promising blood-based approach. Reported here is the analytical validation of MethyLiverDx-Sigma (MLDx-s), an assay that detects methylated RNF135 and DNMT3A in bisulfite-converted plasma cfDNA by methylation-specific PCR with high-resolution melting (HRM), with GAPDH as an endogenous control. Performance was evaluated following CLSI EP05-A3, EP07, EP12-A2, and EP37. Precision of quantification cycle (C q ) and melting peak temperature (T m ) was assessed by variance-component analysis within one site and across two sites and two operators. Because precision studies used bulk bisulfite-converted reference DNA, the reported coefficients of variation (CVs) primarily characterize the PCR-HRM detection module; end-to-end variability in clinical plasma specimens may be higher. Interference and cross-reactivity were evaluated in low-positive and contrived-negative samples against reproducibility-derived limits, with dose-response testing of reactive substances. Detection was 100% at both levels, and every run met control-validity criteria. C q repeatability CVs ranged from 0.53% to 1.68%, and total reproducibility CVs ranged from 1.10% to 2.37%; all T m CVs were ≤0.20%. All 18 interferents and 16 microbial cross-reactants evaluated in low-positive samples met the predefined acceptance criteria. In negative samples, hemoglobin, SARS-CoV-2, and measles virus produced concentration-dependent non-specific amplification, and dose-response testing established their respective no-effect concentrations. These findings characterize the analytical precision and multisite reproducibility of the PCR-HRM detection module and the analytical specificity of MLDx-s, complementing its previously reported clinical performance for plasma-based HCC detection.",
  "abstract_shown": true,
  "affiliations": [
    "R&D Center, LepiDyne Inc., Seoul, Republic of Korea",
    "R&D Center, LepiDyne Inc., Seoul, Republic of Korea; Interdisciplinary Program of Integrated OMICS for Biomedical Science, Yonsei University, Seoul, Republic of Korea"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Si-Cho Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "Hyunwoo Choi"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiin Chung"
    },
    {
      "affs": [
        0
      ],
      "name": "Seung-Taek Lee"
    },
    {
      "name": "Young-Joon Kim"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4p2r8wg6zkhre.bib",
  "cited_by": 0,
  "doi": "10.1016/j.mcp.2026.102090",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S0890850826000307",
  "id": "4p2r8wg6zkhre",
  "issns": [
    "0890-8508",
    "1096-1194"
  ],
  "landing_url": "https://doi.org/10.1016/j.mcp.2026.102090",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "1306|Cancer Genomics and Diagnostics"
    ]
  ],
  "openalex": "W7223114647",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/4p2r8wg6zkhre.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:47:24Z",
      "native_id": "f6121a1380674f6283fb42e8175d9a4a",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.mcp.2026.102090"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer Genomics and Diagnostics",
      "subfield": "oncology"
    }
  ],
  "title": "Analytical validation of MethyLiverDx-Sigma, a plasma cfDNA methylation assay for hepatocellular carcinoma detection",
  "title_text": "Analytical validation of MethyLiverDx-Sigma, a plasma cfDNA methylation assay for hepatocellular carcinoma detection",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:47:24Z",
  "url": "https://research.draconitic.com/paper/4p2r8wg6zkhre",
  "venue": "Molecular and Cellular Probes",
  "versions": []
}