Evidence map›Paper›PMID 25884197›Full record

ArticleBMC cancer2015

Circulating tumor cells in hepatocellular carcinoma: a pilot study of detection, enumeration, and next-generation sequencing in cases and controls.

Robin K Kelley, Mark Jesus M Magbanua, Timothy M Butler, Eric A Collisson, Jimmy Hwang, Nikoletta Sidiropoulos, Kimberley Evason, Ryan M McWhirter, Bilal Hameed, Elizabeth M Wayne and 3 more

Open access · goldAbstract readClinical Study
In one paragraph

Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 3 pooled it
5.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

78 citing papers in PubMed, 3 syntheses or guidelines pooled it, 123 citations in OpenAlex.

  1. Utility of Liquid Biopsy Analysis in Detection of Hepatocellular Carcinoma, Determination of Prognosis, and Disease Monitoring: A Systematic Review.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2020
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  20. Liquid Liver Biopsy for Disease Diagnosis and Prognosis.Journal of clinical and translational hepatology · 2023
    Review

18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Robin K KelleyHelen Diller Family Comprehensive Cancer Center and The Liver Center, University of California San Francisco (UCSF), 550 16th St., Box 3211, San Francisco, CA, 94143, USA. Katie.kelley@ucsf.edu.
Mark Jesus M MagbanuaHelen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA, 94143, USA. Mark.Magbanua@ucsf.edu.
Timothy M ButlerDepartment of Molecular and Medical Genetics, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Mail Code #L103, Portland, OR, 97239, USA. butlerti@ohsu.edu.
Eric A CollissonHelen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA, 94143, USA. Eric.Collisson@ucsf.edu.
Jimmy HwangHelen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA, 94143, USA. jhwang@cc.ucsf.edu.
Nikoletta SidiropoulosUniversity of Vermont Medical Center, 89 Beaumont Ave., Burlington, VT, 05405, USA. Nikoletta.Sidiropoulos@vtmednet.org.
Kimberley EvasonDepartment of Pathology, UCSF, 513 Parnassus Ave., San Francisco, CA, 94143, USA. Kimberley.Evason@ucsfmedctr.org.
Ryan M McWhirterHelen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA, 94143, USA. McWhirterR@cc.ucsf.edu.
Bilal HameedDivision of Hepatology and Liver Transplant, UCSF, 513 Parnassus Ave., S-357, San Francisco, CA, 94143, USA. Bilal.Hameed@ucsf.edu.
Elizabeth M WayneDepartment of Transplantation-Abdominal, UCSF, 513 Parnassus Ave., S-357, San Francisco, CA, 94143, USA. Elizabeth.Wayne@ucsf.edu.
Francis Y YaoDivision of Hepatology and Liver Transplant and The Liver Center, UCSF, 513 Parnassus Ave., S-357, San Francisco, CA, 94143, USA. Francis.Yao@ucsf.edu.
Alan P VenookHelen Diller Family Comprehensive Cancer Center and The Liver Center, University of California San Francisco (UCSF), 550 16th St., Box 3211, San Francisco, CA, 94143, USA. venook@cc.ucsf.edu.
John W ParkHelen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA, 94143, USA. jpark@cc.ucsf.edu.
UCSF Helen Diller Family Comprehensive Cancer Center · USUniversity of California, San Francisco · USOregon Health & Science University · USUniversity of Vermont Medical Center · US

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Holger Willenbring · 1986 to 2026
$30.7M
Program in Molecular and Cellular BiosciencesT32GM071338 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI MASLEN, CHERYL L · 2005 to 2020
$3.5M
Risk-Benefit Trade-Offs for Whole Genome SequencingR01HG007063 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PHILLIPS, KATHRYN A · 2013 to 2016
$2.5M
Mechanisms and modifiers of beta-catenin-induced hepatic tumorigenesisK08CA172288 · NCI · UNIVERSITY OF UTAH · PI EVASON, KIMBERLEY JANE · 2013 to 2017
$754k
NCI NIH HHS 1K08CA172288-01A1NCI NIH HHS K08 CA172288NHGRI NIH HHS R01 HG007063NHGRI NIH HHS R01HG007063NIDDK NIH HHS P30 DK026743NIGMS NIH HHS T32 GM071338
6 · The paper itself

Abstract

backgroundCirculating biomarkers are urgently needed in hepatocellular carcinoma (HCC). The aims of this study were to determine the feasibility of detecting and isolating circulating tumor cells (CTCs) in HCC patients using enrichment for epithelial cell adhesion molecule (EpCAM) expression, to examine their prognostic value, and to explore CTC-based DNA sequencing in metastatic HCC patients compared to a control cohort with non-malignant liver diseases (NMLD).

methodsWhole blood was obtained from patients with metastatic HCC or NMLD. CTCs were enumerated by CellSearch then purified by immunomagnetic EpCAM enrichment and fluorescence-activated cell sorting. Targeted ion semiconductor sequencing was performed on whole genome-amplified DNA from CTCs, tumor specimens, and peripheral blood mononuclear cells (PBMC) when available.

resultsTwenty HCC and 10 NMLD patients enrolled. CTCs ≥ 2/7.5 mL were detected in 7/20 (35%, 95% confidence interval: 12%, 60%) HCC and 0/9 eligible NMLD (p = 0.04). CTCs ≥ 1/7.5 mL was associated with alpha-fetoprotein ≥ 400 ng/mL (p = 0.008) and vascular invasion (p = 0.009). Sequencing of CTC DNA identified characteristic HCC mutations. The proportion with ≥ 100x coverage depth was lower in CTCs (43%) than tumor or PBMC (87%) (p < 0.025). Low frequency variants were higher in CTCs (p < 0.001).

conclusionsCTCs are detectable by EpCAM enrichment in metastatic HCC, without confounding false positive background from NMLD. CTC detection was associated with poor prognostic factors. Sequencing of CTC DNA identified known HCC mutations but more low-frequency variants and lower coverage depth than FFPE or PBMC.

Indexed as

Neoplastic Cells, CirculatingAgedAged, 80 and overAntigens, NeoplasmCarcinoma, HepatocellularCell Adhesion MoleculesEpithelial Cell Adhesion MoleculeEpithelial-Mesenchymal TransitionFemaleHigh-Throughput Nucleotide SequencingHumansKaplan-Meier EstimateLiver DiseasesLiver NeoplasmsMaleMiddle AgedAntigens, NeoplasmCell Adhesion MoleculesEPCAM protein, humanEpithelial Cell Adhesion Molecule

Identifiers

PMID25884197
PMCPMC4399150
OpenAlexW2004867383

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.