# Digital Biomarkers for Precision Early Detection of Lung Cancer: Integrating AI‐Driven Multi‐Omics Into Clinical Pathways

**Authors:** Fan Bu, Zhi‐Qiang Ling

PMC · DOI: 10.1002/cam4.71578 · Cancer Medicine · 2026-02-05

## TL;DR

This review explores how combining AI and multi-omics data can improve early detection of lung cancer and support personalized treatment strategies.

## Contribution

The paper systematically evaluates AI-driven multi-omics biomarkers for early lung cancer detection and their integration into clinical pathways.

## Key findings

- Multi-omics strategies are accelerating the discovery of molecular signatures for early lung cancer detection.
- AI methods help extract patterns from complex data, improving risk stratification and treatment planning.
- Barriers to clinical translation include data heterogeneity, model interpretability, and regulatory challenges.

## Abstract

Lung cancer remains the leading cause of cancer‐related mortality worldwide, highlighting the urgent need for earlier detection within real‐world screening and patient management pathways. Recent advances in multi‐omics technologies have created new opportunities for identifying biomarkers associated with early‐stage lung cancer, particularly in high‐risk populations under clinical surveillance.

This review systematically evaluates early diagnostic biomarkers across multiple omics layers, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiomics. It also summarises the application of artificial intelligence (AI), particularly machine learning and deep learning approaches, for integrating and analysing complex multi‐omics datasets to support biomarker discovery and clinical decision‐making.

Multi‐omics strategies are accelerating the identification of molecular signatures relevant to early lung cancer detection. AI‐driven methods enable the extraction of latent patterns from high‐dimensional data, facilitating risk stratification, diagnostic refinement, histological subtyping and treatment planning. The review highlights the clinical utility of these biomarkers and their potential incorporation into screening algorithms, as well as the development of AI‐based clinical decision support systems (CDSS) aligned with real‐world clinical workflows. However, major barriers to clinical translation remain, including multi‐centre data heterogeneity, limited model interpretability affecting clinical trust, regulatory and cost‐effectiveness challenges and insufficient validation in prospective cohorts.

Emerging technologies, such as single‐cell and spatial multi‐omics, along with federated learning frameworks, offer promising solutions to bridge the gap between computational discovery and clinical implementation. The integration of AI and multi‐omics approaches has the potential to advance risk‐adapted and personalised early detection strategies for lung cancer.

## Linked entities

- **Diseases:** lung cancer (MONDO:0005138)

## Full-text entities

- **Genes:** SOX17 (SRY-box transcription factor 17) [NCBI Gene 64321] {aka PPH7, VUR3}, MIR2114 (microRNA 2114) [NCBI Gene 100313839], MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, ETHE1 (ETHE1 persulfide dioxygenase) [NCBI Gene 23474] {aka HSCO, YF13H12}, ROS1 (ROS proto-oncogene 1, receptor tyrosine kinase) [NCBI Gene 6098] {aka MCF3, ROS, c-ros-1}, SLTM (SAFB like transcription modulator) [NCBI Gene 79811] {aka Met}, HSPD1 (heat shock protein family D (Hsp60) member 1) [NCBI Gene 3329] {aka CPN60, GROEL, HLD4, HSP-60, HSP60, HSP65}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, SERPINA1 (serpin family A member 1) [NCBI Gene 5265] {aka A1A, A1AT, AAT, PI, PI1, PRO2275}, TACC3 (transforming acidic coiled-coil containing protein 3) [NCBI Gene 10460] {aka ERIC-1, ERIC1, Tacc4, maskin}, MIR449C (microRNA 449c) [NCBI Gene 100313923] {aka mir-449c}, RBP4 (retinol binding protein 4) [NCBI Gene 5950] {aka MCOPCB10, RDCCAS}, MUC16 (mucin 16, cell surface associated) [NCBI Gene 94025] {aka CA125}, GRP (gastrin releasing peptide) [NCBI Gene 2922] {aka BN, GRP-10, preproGRP, proGRP}, SERPINA4 (serpin family A member 4) [NCBI Gene 5267] {aka KAL, KLST, KST, PI-4, PI4, kallistatin}, SHOX2 (SHOX homeobox 2) [NCBI Gene 6474] {aka OG12, OG12X, SHOT}, PDGFRA (platelet derived growth factor receptor alpha) [NCBI Gene 5156] {aka CD140A, PDGFR-2, PDGFR2}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, SERPINA3 (serpin family A member 3) [NCBI Gene 12] {aka AACT, ACT, GIG24, GIG25}, MIR3662 (microRNA 3662) [NCBI Gene 100500880] {aka mir-3662}, HOTAIR (HOX transcript antisense RNA) [NCBI Gene 100124700] {aka HOXAS, HOXC-AS4, HOXC11-AS1, NCRNA00072}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, MIR221 (microRNA 221) [NCBI Gene 407006] {aka MIRN221, miRNA221, mir-221}, YEATS2 (YEATS domain containing 2) [NCBI Gene 55689] {aka FAME4}, UNCX (UNC homeobox) [NCBI Gene 340260] {aka UNCX4.1}, MIR375 (microRNA 375) [NCBI Gene 494324] {aka MIRN375, hsa-mir-375, miRNA375, mir-375}, PTGDR (prostaglandin D2 receptor) [NCBI Gene 5729] {aka AS1, ASRT1, DP, DP1, PTGDR1}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, ENO1 (enolase 1) [NCBI Gene 2023] {aka ENO1-IT1, ENO1L1, HEL-S-17, MPB1, NNE, PPH}, GAS5 (growth arrest specific 5) [NCBI Gene 60674] {aka NCRNA00030, SNHG2}, MIR944 (microRNA 944) [NCBI Gene 100126340] {aka MIRN944, hsa-mir-944, mir-944}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, RUNX3 (RUNX family transcription factor 3) [NCBI Gene 864] {aka AML2, CBFA3, PEBP2aC}, RB1 (RB transcriptional corepressor 1) [NCBI Gene 5925] {aka OSRC, PPP1R130, RB, p105-Rb, p110-RB1, pRb}, RET (ret proto-oncogene) [NCBI Gene 5979] {aka CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1}, CISH (cytokine inducible SH2 containing protein) [NCBI Gene 1154] {aka BACTS2, CIS, CIS-1, G18, SOCS}, FGFR1 (fibroblast growth factor receptor 1) [NCBI Gene 2260] {aka BFGFR, CD331, CEK, ECCL, FGFBR, FGFR-1}, KRT19 (keratin 19) [NCBI Gene 3880] {aka CK19, K19, K1CS}, AJAP1 (adherens junctions associated protein 1) [NCBI Gene 55966] {aka MOT8, SHREW-1, SHREW1}, MGMT (O-6-methylguanine-DNA methyltransferase) [NCBI Gene 4255], APCS (amyloid P component, serum) [NCBI Gene 325] {aka HEL-S-92n, PTX2, SAP}, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290] {aka CCM4, CLAPO, CLOVE, CWS5, HMH, MCAP}, EPHA2 (EPH receptor A2) [NCBI Gene 1969] {aka ARCC2, CTPA, CTPP1, CTRCT6, ECK}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, HRAS (HRas proto-oncogene, GTPase) [NCBI Gene 3265] {aka C-BAS/HAS, C-H-RAS, C-HA-RAS1, CTLO, H-RASIDX, HAMSV}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, STK11 (serine/threonine kinase 11) [NCBI Gene 6794] {aka LKB1, PJS, hLKB1}, TAC1 (tachykinin precursor 1) [NCBI Gene 6863] {aka Hs.2563, NK2, NKNA, NPK, TAC2}, MIR223 (microRNA 223) [NCBI Gene 407008] {aka MIRN223, miRNA223, mir-223}, MIR20A (microRNA 20a) [NCBI Gene 406982] {aka C13orf25, MIR20, MIRH1, MIRHG1, MIRN20, MIRN20A}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, MIR190B (microRNA 190b) [NCBI Gene 100126346] {aka MIRN190B, mir-190b}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, ENO2 (enolase 2) [NCBI Gene 2026] {aka HEL-S-279, NSE}, HOXA9 (homeobox A9) [NCBI Gene 3205] {aka ABD-B, HOX1, HOX1.7, HOX1G}
- **Diseases:** invasive carcinoma (MESH:D009361), AI (MESH:C538142), bronchial epithelial hyperplasia (MESH:D017573), benign (MESH:D009369), ovarian cancer (MESH:D010051), XAI (MESH:C538243), metaplasia (MESH:D008679), Lung Cancer (MESH:D008175), adenocarcinoma (MESH:D000230), I (MESH:D006969), SCLC (MESH:D055752), stage I (MESH:D062706), dysplasia (MESH:D015792), bacterial (MESH:D001424), LDCT (MESH:C000719218), LUSC (MESH:D002294), benign lesions (MESH:D001932), NSCLC (MESH:D002289), microsatellite instability (MESH:D053842), PC (MESH:C535298), nodules (MESH:D016606), CDSS (MESH:D020195), LUAD (MESH:D000077192), MRM (MESH:D000069076), breast cancer (MESH:D001943), lung lesions (MESH:D008171), lung carcinogenesis (MESH:D063646), metastases (MESH:D009362), carcinoma in situ (MESH:D002278), prostate cancer (MESH:D011471)
- **Chemicals:** sphingomyelin (MESH:D013109), 2-hydroxyacetaldehyde (-), 2-butanone (MESH:C005222), creatinine (MESH:D003404), Lactate (MESH:D019344), lysophosphatidylcholine (MESH:D008244), N-acetylglucosamine (MESH:D000117), glucose (MESH:D005947), PE (MESH:C483858), cholesteryl ester (MESH:D002788), Phospholipids (MESH:D010743), lysophosphatidylethanolamine (MESH:C008301), haematoxylin (MESH:D006416), malondialdehyde (MESH:D008315), creatine (MESH:D003401), acrolein (MESH:D000171), 4-HHE (MESH:C063409), diacylglycerols (MESH:D004075), 3-hydroxy-2-butanone (MESH:D000093), SM (MESH:D012493), oxygen (MESH:D010100), eosin (MESH:D004801), H&amp;E (MESH:D006371), VOC (MESH:D055549), PC (MESH:D010713)
- **Species:** Veillonella (genus) [taxon 29465], Selenomonas (genus) [taxon 970], Homo sapiens (human, species) [taxon 9606], Bacteroidia (class) [taxon 200643], Megasphaera (genus) [taxon 906], Streptococcus (genus) [taxon 1301], Nicotiana tabacum (American tobacco, species) [taxon 4097], Clostridium (genus) [taxon 1485]

## Full text

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## References

143 references — full list in the complete paper: https://tomesphere.com/paper/PMC12877424/full.md

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Source: https://tomesphere.com/paper/PMC12877424