Evidence map›Paper›PMID 40072122›Full record

ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2025

Optimizing Biomarker Models for Biologically Heterogeneous Cancers: A Nested Model Approach for Lung Cancer.

Palina Woodhouse, Laurel Jackson, Michael N Kammer, Caroline M Godfrey, Sanja Antic, Yong Zou, Patrick Meyers, Susan H Gawel, Fabien Maldonado, Eric L Grogan and 2 more

Abstract read
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, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Leveraging Commercially Available Protein Assays as Biomarkers for Lung Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026
    Article
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

12 authors.

Palina WoodhouseVanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0000-2440-3750
Laurel JacksonAbbott Diagnostics Division, Abbott Park, Illinois.ORCID 0000-0002-0491-9079
Michael N KammerVanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0001-7912-8450
Caroline M GodfreyVanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-4090-2338
Sanja AnticVanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-6948-8003
Yong ZouVanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0007-3897-0087
Patrick MeyersVanderbilt University Medical Center, Nashville, Tennessee.ORCID 0009-0009-3317-2224
Susan H GawelAbbott Diagnostics Division, Abbott Park, Illinois.ORCID 0000-0003-3295-7539
Fabien MaldonadoVanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-6504-2063
Eric L GroganVanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-3886-9399
Gerard J DavisAbbott Diagnostics Division, Abbott Park, Illinois.ORCID 0000-0002-4149-1999
Stephen A DeppenVanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-3661-662X

Funding

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
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 Cancer Institute (NCI) R01CA252964National Cancer Institute (NCI) U01CA152662NCI NIH HHS R01 CA252964NCI NIH HHS U01 CA152662
6 · The paper itself

Abstract

backgroundThe heterogeneous biology of cancer subtypes, especially in lung cancer, poses significant challenges for biomarker development. Standard model building techniques often fall short in accurately incorporating various histologic subtypes because of their diverse biological characteristics. This study explores a nested biomarker model to address this issue, aiming to improve lung cancer early detection.

methodsThe study included 337 patients from two clinical sites. Blood biomarkers were analyzed and various statistical methods employed to develop a nested model. This model was designed to account for the biological heterogeneity across histologic subtypes, compared against traditional logistic regression models.

resultsThe patient cohort included a range of malignant and benign nodules and included different cancer subtypes reflecting lung cancer heterogeneity. The nested model had comparable performance overall with the Mayo Clinic model and a standard logistic regression model with an AUC of 77.6 (95% confidence interval, 72.2-83.0) in training and 77.3 (95% confidence interval, 65.8-88.9) in testing. The nested subtype versus benign model had the best performance in the training set overall and had a particular advantage for small cell subtype prediction.

conclusionsThis study highlights the challenges cancer heterogeneity present for biomarker development and the potential for nested biomarker models to improve early cancer detection. Validation of this approach in larger cohorts is essential to prove its predictive benefit in biologically diverse cancers. IMPACT: This work addresses the challenge of biological heterogeneity in biomarker development. A nested modeling approach may assist in developing more effective multicancer early detection strategies.

Indexed as

Biomarkers, TumorLung NeoplasmsAgedEarly Detection of CancerFemaleHumansMaleMiddle AgedBiomarkers, Tumor

Identifiers

PMID40072122
PMCPMC12483149

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Registered trials

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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 OpenQuestion graph.