Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Revealing Causal Protein Biomarkers and Potential Therapeutic Targets for Histologic-Specific Lung Cancer

Sun, Wen ; Liu, Jingyang ; Li, Jiayan ; Li, Ning ; Zhang, Xiaoyu ; Li, Changwei ; Zhang, Li ; He, Yan ; Wu, Lijuan and Wang, Xiao LU , et al. (2025) In Journal of Cellular and Molecular Medicine 29(23).
Abstract

Considering the distinct etiological pathways and molecular characteristics of different lung cancer subtypes, it is crucial to develop subtype-specific prevention strategies and therapeutic targets. This study aimed to identify protein biomarkers and potential therapeutic targets for specific subtypes of lung cancer by integrating population-based observational studies and Mendelian randomisation (MR) analyses. The cohort study was conducted in the UK Biobank, including about 47,000 participants whose blood samples were measured for 2,923 unique proteins and who were followed for the development of lung cancer. Two-sample MR was performed leveraging publicly available data from genome-wide association studies (GWAS) and protein... (More)

Considering the distinct etiological pathways and molecular characteristics of different lung cancer subtypes, it is crucial to develop subtype-specific prevention strategies and therapeutic targets. This study aimed to identify protein biomarkers and potential therapeutic targets for specific subtypes of lung cancer by integrating population-based observational studies and Mendelian randomisation (MR) analyses. The cohort study was conducted in the UK Biobank, including about 47,000 participants whose blood samples were measured for 2,923 unique proteins and who were followed for the development of lung cancer. Two-sample MR was performed leveraging publicly available data from genome-wide association studies (GWAS) and protein quantitative trait loci (pQTL). Proteins were prioritised based on consistent associations across logistic regression, MR, transcriptomic validation and sensitivity analyses. Tier 1 proteins passed all evaluations, including GP1BA (squamous cell carcinoma) and ACADSB (small cell carcinoma). Tier 2 proteins, supported by transcriptomic evidence but not sensitivity analyses, included AGRN, ITGB2, SEPTIN3 (adenocarcinoma) and DPP10 (squamous cell carcinoma). Tier 3 proteins, supported by logistic regression and MR only, included CD5L, GNPDA, ACAN, C7, DMP1, HEPH, CEACAM6, COX6B1, CPXM2 and IL12RB2. Druggability evaluation suggests that existing drugs targeting ITGB2, GP1BA, ACADSB and COX6B1 could potentially be repurposed for the treatment of specific lung cancer subtypes.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
drug target, lung cancer, Mendelian randomization, protein, protein quantitative trait loci
in
Journal of Cellular and Molecular Medicine
volume
29
issue
23
article number
e70866
publisher
Wiley-Blackwell
external identifiers
  • pmid:41340014
  • scopus:105023740142
ISSN
1582-1838
DOI
10.1111/jcmm.70866
language
English
LU publication?
yes
id
28aefdf7-b88f-4afe-b0e2-fad3593cd24f
date added to LUP
2026-01-12 14:02:25
date last changed
2026-01-13 03:00:02
@article{28aefdf7-b88f-4afe-b0e2-fad3593cd24f,
  abstract     = {{<p>Considering the distinct etiological pathways and molecular characteristics of different lung cancer subtypes, it is crucial to develop subtype-specific prevention strategies and therapeutic targets. This study aimed to identify protein biomarkers and potential therapeutic targets for specific subtypes of lung cancer by integrating population-based observational studies and Mendelian randomisation (MR) analyses. The cohort study was conducted in the UK Biobank, including about 47,000 participants whose blood samples were measured for 2,923 unique proteins and who were followed for the development of lung cancer. Two-sample MR was performed leveraging publicly available data from genome-wide association studies (GWAS) and protein quantitative trait loci (pQTL). Proteins were prioritised based on consistent associations across logistic regression, MR, transcriptomic validation and sensitivity analyses. Tier 1 proteins passed all evaluations, including GP1BA (squamous cell carcinoma) and ACADSB (small cell carcinoma). Tier 2 proteins, supported by transcriptomic evidence but not sensitivity analyses, included AGRN, ITGB2, SEPTIN3 (adenocarcinoma) and DPP10 (squamous cell carcinoma). Tier 3 proteins, supported by logistic regression and MR only, included CD5L, GNPDA, ACAN, C7, DMP1, HEPH, CEACAM6, COX6B1, CPXM2 and IL12RB2. Druggability evaluation suggests that existing drugs targeting ITGB2, GP1BA, ACADSB and COX6B1 could potentially be repurposed for the treatment of specific lung cancer subtypes.</p>}},
  author       = {{Sun, Wen and Liu, Jingyang and Li, Jiayan and Li, Ning and Zhang, Xiaoyu and Li, Changwei and Zhang, Li and He, Yan and Wu, Lijuan and Wang, Xiao and Ji, Jianguang and Zheng, Deqiang}},
  issn         = {{1582-1838}},
  keywords     = {{drug target; lung cancer; Mendelian randomization; protein; protein quantitative trait loci}},
  language     = {{eng}},
  number       = {{23}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Cellular and Molecular Medicine}},
  title        = {{Revealing Causal Protein Biomarkers and Potential Therapeutic Targets for Histologic-Specific Lung Cancer}},
  url          = {{http://dx.doi.org/10.1111/jcmm.70866}},
  doi          = {{10.1111/jcmm.70866}},
  volume       = {{29}},
  year         = {{2025}},
}