# LungPanelNet: a machine learning-based approach for the early prediction and differentiation of non-small cell lung cancer

**Authors:** Li Zhao, Mei Li, Juju Qi, Lingling Wan

PMC · DOI: 10.3389/fonc.2025.1702589 · 2026-01-13

## TL;DR

LungPanelNet is a machine learning model that uses blood markers to detect non-small cell lung cancer early and distinguish it from benign lung conditions.

## Contribution

A novel deep neural network model using serum tumor markers for early NSCLC detection and differentiation from benign conditions.

## Key findings

- LungPanelNet achieved an AUC-ROC of 0.92, with 89.3% accuracy in distinguishing NSCLC from benign conditions.
- SCCA and CYFRA21-1 were identified as the most significant predictors in the model.

## Abstract

Non-small cell lung cancer (NSCLC) represents a major global health challenge, primarily due to its frequent diagnosis at advanced stages, which significantly limits therapeutic efficacy and results in poor survival outcomes. A critical unmet need exists for non-invasive, accurate diagnostic tools for early detection. Objective: This study aimed to develop and validate a robust machine learning model based on a panel of serum tumor markers for the early prediction of NSCLC and its differentiation from benign pulmonary conditions. Methods: In this retrospective cohort study, we recruited 2,283 participants, including 1,339 with NSCLC, 313 with pneumonia, 260 with biopsy-confirmed benign lesions, and 371 with other benign lung masses. Serum levels of six key tumor markers—Squamous Cell Carcinoma Antigen (SCCA), Carcinoembryonic Antigen (CEA), Cancer Antigen 125 (CA-125), Cytokeratin 19 Fragment (CYFRA21-1), Neuron-Specific Enolase (NSE), and Pro-Gastrin-Releasing Peptide (ProGRP)—were quantified, and a custom deep neural network, LungPanelNet, was constructed for the classification task. Results: The model demonstrated superior predictive performance on an independent testing set, achieving an area under the receiver operating characteristic curve (AUC-ROC) of 0.92 (95% CI: 0.88–0.96), with an accuracy of 89.3%, a sensitivity of 91.5%, and a specificity of 87.8%. Feature importance analysis identified SCCA and CYFRA21-1 as the most significant predictors. Conclusion: Our findings demonstrate that a machine learning model integrating a panel of serum tumor markers can effectively distinguish NSCLC from a spectrum of benign pulmonary conditions with high accuracy. This approach shows promise as a clinical decision-support tool, though further validation in larger, prospective, multi-center cohorts is warranted. This was a retrospective cohort study without clinical trial registration.

## Linked entities

- **Diseases:** non-small cell lung cancer (MONDO:0005233), pneumonia (MONDO:0005249)

## Full-text entities

- **Genes:** MUC16 (mucin 16, cell surface associated) [NCBI Gene 94025] {aka CA125}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, ENO2 (enolase 2) [NCBI Gene 2026] {aka HEL-S-279, NSE}
- **Diseases:** benign lesions (MESH:D001932), NSCLC (MESH:D002289), SCCA (MESH:D002294), tumor (MESH:D009369), pneumonia (MESH:D011014), benign lung masses (MESH:D008171)
- **Chemicals:** Pro-Gastrin-Releasing Peptide (-)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12834828/full.md

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Source: https://tomesphere.com/paper/PMC12834828