Evidence map›Paper›PMID 42259736›Full record

ArticleHPB : the official journal of the International Hepato Pancreato Biliary Association2026

Using cell-free DNA tumor methylation score to detect and monitor cholangiocarcinoma.

Salar Javanshir, Isabella Angeli-Pahim, Pavan Iyengar, Anastasia Chambers, Iulia M Smarandache, Rishiraj Ganguli, Abhishek Shrestha, Jessica Squadrito, Adriana Abreu, Gabrielle Suchan and 7 more

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Article in HPB : the official journal of the International Hepato Pancreato Biliary Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

17 authors.

Salar JavanshirDepartment of Surgery, University of Florida, USA.
Isabella Angeli-PahimDepartment of Surgery, University of Florida, USA.
Pavan IyengarDepartment of Surgery, University of Florida, USA.
Anastasia ChambersDepartment of Surgery, University of Florida, USA.
Iulia M SmarandacheDepartment of Surgery, University of Florida, USA.
Rishiraj GanguliDepartment of Surgery, University of Florida, USA.
Abhishek ShresthaDepartment of Surgery, University of Florida, USA.
Jessica SquadritoDepartment of Surgery, University of Florida, USA.
Adriana AbreuDepartment of Surgery, University of Florida, USA.
Gabrielle SuchanDepartment of Surgery, University of Florida, USA.
Carl RizkDepartment of Surgery, University of Florida, USA.
Fahreddin PalazDepartment of Surgery, University of Florida, USA.
Steven J HughesDepartment of Surgery, University of Florida, USA.
Ilyas SahinDepartment of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, USA.
Joseph R GrajoDepartment of Radiology, University of Florida, USA.
Sergio DuarteDepartment of Surgery, University of Florida, USA.
Ali ZarrinparDepartment of Surgery, University of Florida, USA. Electronic address: ali.zarrinpar@surgery.ufl.edu.

Funding

Mentoring Patient-Oriented Research in Immune Response in TransplantationK24AI187634 · NIAID · UNIVERSITY OF FLORIDA · PI ALI ZARRINPAR · 2025 to 2026
$251k
NIAID NIH HHS K24 AI187634
6 · The paper itself

Abstract

backgroundCholangiocarcinoma (CCA) is characterized by late or unclear diagnosis, high recurrence rates, and limited options for noninvasive disease monitoring. The widely used serum biomarker CA 19-9 has suboptimal sensitivity and specificity, underscoring the need for more accurate and reliable quantitative measures of tumor burden. Cell-free DNA (cfDNA) methylation represents a promising approach for longitudinal disease monitoring.

methodsIn this single-center cohort study, we evaluated a cfDNA methylation-based Tumor Methylation Score (TMS) for detecting and monitoring CCA. Twenty-five patients with histologically confirmed CCA and twelve controls with benign hepatobiliary conditions were enrolled, yielding 100 plasma samples and 26 tissue samples. cfDNA methylation was quantified across 537 cancer-associated CpG loci by qPCR method, and TMS was calculated from the difference in methylation in paired plasma and buffy coat samples. For tissue samples, TMS was calculated by quantifying methylation in tumor and background liver separately. Response to treatment was assessed using blinded radiographic review. Tissue-based validation was performed using The Cancer Genome Atlas and 4 additional GEO cohorts. Finally, cellular pathways associated with the panel genes were explored using the Ingenuity Pathway Analysis (IPA).

resultsTMS was significantly elevated in CCA samples compared with controls in both tissue (P = 0.007) and plasma (P < 0.0001). Plasma TMS distinguished CCA from controls with a sensitivity of 74.3% and specificity of 80% (AUC = 0.823), while CA 19-9 showed no discriminatory value. TMS decreased consistently following curative resection. Longitudinal changes in TMS (ΔTMS) robustly distinguished radiographic progression from non-progression during systemic therapy (AUC = 0.968), outperforming ΔCA 19-9. Tissue-based analyses across independent cohorts confirmed cancer specificity and association with adverse outcomes. IPA identified HOXA9 as a significantly altered gene implicated in CCA carcinogenesis.

conclusionsQuantitative cfDNA methylation monitoring using TMS is feasible and accurately reflects dynamic tumor burden in CCA. TMS may serve as a complementary adjunct to imaging and CA 19-9 for diagnosis, prognosis, and longitudinal disease monitoring, warranting validation in larger prospective studies.

Indexed as

Bile Duct NeoplasmsBiomarkers, TumorCholangiocarcinomaCirculating Tumor DNADNA MethylationAgedCase-Control StudiesFemaleHumansMaleMiddle AgedPredictive Value of TestsReproducibility of ResultsBiomarkers, TumorCirculating Tumor DNA

Identifiers

PMID42259736
PMCPMC13445305

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.