Evidence map›Paper›PMID 42233870›Full record

ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2026

Leveraging Commercially Available Protein Assays as Biomarkers for Lung Cancer.

Kevin Connor McGann, Palina Woodhouse, Heidi Chen, Michael N Kammer, Hudson Michael Holmes, Camden Lopez, Harvey I Pass, Jun-Chieh J Tsay, Marc E Lenburg, Steven M Dubinett and 19 more

Abstract readMulticenter Study
In one paragraph

Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

29 authors.

Kevin Connor McGannDepartment of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0005-3575-6873
Palina WoodhouseDepartment of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0000-2440-3750
Heidi ChenDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-8817-7139
Michael N KammerInstitut de recherche en informatique de Toulouse, Université Toulouse Capitole, Toulouse, France.ORCID 0000-0001-7912-8450
Hudson Michael HolmesDepartment of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0005-3700-2354
Camden LopezDepartment of Biostatistics, University of Washington, Seattle, Washington.ORCID 0000-0003-4516-8088
Harvey I PassDepartment of Thoracic Surgery, New York University Langone Health, New York, New York.ORCID 0000-0003-3222-3471
Jun-Chieh J TsayDepartment of Medicine, New York University Langone Health, New York, New York.ORCID 0000-0002-2282-2510
Marc E LenburgDepartment of Medicine, Chobanian and Avedisian School of Medicine, Boston University, Boston, Massachusetts.ORCID 0000-0002-5760-4708
Steven M DubinettDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.ORCID 0000-0003-3656-8039
James C WilleyDepartment of Medicine, University of Toledo Health Sciences Campus, Toledo, Ohio.ORCID 0000-0002-1192-6824
James G HermanDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.ORCID 0000-0001-8102-1740
Matthew B SchabathDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.ORCID 0000-0003-3241-3216
Timothy A KhalilDepartment of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0009-9469-9353
Yong ZouDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0007-3897-0087
Melissa H PotterDepartment of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0006-1163-0800
Sheau-Chiann ChenDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-5574-1434
Samson A ArgawDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0003-7494-9411
Patrick MeyersDepartment of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0009-3317-2224
Sam FischerDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0004-5435-8080
Carolyn TranDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0004-9443-886X
Yency J ForeroDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0003-3889-4081
Sanja AnticDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-6948-8003
Rafael PaezDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-3938-8968
Eardi LilaDepartment of Biostatistics, University of Washington, Seattle, Washington.ORCID 0000-0002-9199-392X
Anna E BarónDepartment of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0002-7949-4343
Fabien MaldonadoDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-6504-2063
Stephen A DeppenDepartment of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-3661-662X
Eric L GroganDepartment of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-3886-9399

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5M
Validation of Biomarkers of Risk for the Early Detection of Lung CancerU01CA152662 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DEPPEN, STEPHEN, GROGAN, ERIC L · 2010 to 2025
$12.8M
Quantitative Imaging Clinical Validation Center at Moffitt Cancer CenterU01CA200464 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI JOHN J HEINE, Matthew B. Schabath · 2016 to 2026
$9.2M
Clinical Utility of Biomarkers Driven Management of Indeterminate Pulmonary NodulesR01CA252964 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Eric L Grogan, Alexander Mark Kaizer · 2021 to 2026
$3.3M
National Institutes of Health (NIH) 5T32CA106183National Institutes of Health (NIH) R01CA252964National Institutes of Health (NIH) U01CA152662NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA252964NCI NIH HHS U01 CA152662NCI NIH HHS U01 CA200464
6 · The paper itself

Abstract

backgroundLung cancer remains the leading cause of cancer mortality, yet blood-based biomarkers are not routinely used in diagnosis. This study evaluated four commercial blood protein assays, originally validated for other indications, in indeterminate pulmonary nodules (IPN).

methodsUsing a prospective specimen collection, retrospective blinded evaluation design, samples were collected from patients with screening-detected, incidental, or symptomatic IPNs. Cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), and human epididymis protein 4 (HE-4) concentrations were quantified on commercial immunoassays. Logistic regression models were developed using internal training (Train), external testing (Test), and combined reestimation (Train + Test) cohorts and externally validated in an outcome-blinded multicenter cohort (Lung Team Project-2, LTP-2).

resultsThis study included 816 patients: 371 in Train, 166 in Test, and 279 in LTP-2. Malignancy rates were 54%, 44%, and 64%, respectively. In Train + Test, the area under the receiver operating curve (AUC) for lung cancer was 0.60 (95% confidence interval, 0.56-0.65) for CYFRA 21-1, 0.62 (0.58-0.67) for CEA, 0.60 (0.55-0.65) for CA-125, and 0.65 (0.60-0.70) for HE-4. In LTP-2, AUCs were 0.63 (0.56-0.70), 0.64 (0.57-0.70), 0.48 (0.40-0.55), and 0.61 (0.54-0.68), respectively. Combining all four biomarkers yielded an AUC of 0.70 (0.65-0.74) in Train + Test and 0.61 (0.54-0.68) in LTP-2.

conclusionsIn the first biomarker study reporting external validation in LTP-2, CYFRA 21-1, CEA, CA-125, and HE-4 demonstrated diagnostic value in IPNs. IMPACT: By leveraging commercial assays, this study highlights opportunities to enhance lung cancer risk stratification using widely available diagnostics that could be rapidly integrated into clinical workflows.

Indexed as

Biomarkers, TumorLung NeoplasmsAgedAntigens, NeoplasmCA-125 AntigenCarcinoembryonic AntigenFemaleHumansKeratin-19MaleMiddle AgedProspective StudiesRetrospective StudiesWAP Four-Disulfide Core Domain Protein 2antigen CYFRA21.1Antigens, NeoplasmBiomarkers, TumorCA-125 AntigenCarcinoembryonic AntigenKeratin-19WAP Four-Disulfide Core Domain Protein 2WFDC2 protein, human

Identifiers

PMID42233870
PMCPMC13277784

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