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Integrating genomics and proteomics data to identify candidate plasma biomarkers for lung cancer risk among European descendants

British Journal of Cancer volume 129, pages 1510–1515 (2023)Cite this article

Subjects

Abstract

Background

Plasma proteins are potential biomarkers for complex diseases. We aimed to identify plasma protein biomarkers for lung cancer.

Methods

We investigated genetically predicted plasma levels of 1130 proteins in association with lung cancer risk among 29,266 cases and 56,450 controls of European descent. For proteins significantly associated with lung cancer risk, we evaluated associations of genetically predicted expression of their coding genes with the risk of lung cancer.

Results

Nine proteins were identified with genetically predicted plasma levels significantly associated with overall lung cancer risk at a false discovery rate (FDR) of <0.05. Proteins C2, MICA, AIF1, and CTSH were associated with increased lung cancer risk, while proteins SFTPB, HLA-DQA2, MICB, NRP1, and GMFG were associated with decreased lung cancer risk. Stratified analyses by histological types revealed the cross-subtype consistency of these nine associations and identified an additional protein, ICAM5, significantly associated with lung adenocarcinoma risk (FDR < 0.05). Coding genes of NRP1 and ICAM5 proteins are located at two loci that have never been reported by previous GWAS. Genetically predicted blood levels of genes C2, AIF1, and CTSH were associated with lung cancer risk, in directions consistent with those shown in protein-level analyses.

Conclusion

Identification of novel plasma protein biomarkers provided new insights into the biology of lung cancer.

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Fig. 1: Overall schematic of the present study.

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Data availability

ILCCO data and all GTEx data are publicly available through the database of Genotypes and Phenotypes (dbGaP; Accession No. phs001273.v3.p2; phs000424.v8.p2). Plasma protein prediction models are available from http://nilanjanchatterjeelab.org/pwas.

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Acknowledgements

The authors would like to thank the Advanced Computing Center for Research and Education (ACCRE) at Vanderbilt University and the Rivanna High-Performance Computing (HPC) system at the University of Virginia, which were used to conduct data analyses. We thank Ms. Kathleen Harmeyer for her assistance in preparing the manuscript.

Funding

This work was supported by the National Institutes of Health grant R01CA249863 (to CQ and LJ). The sponsors had no role in the study design, in the collection, analysis, or interpretation of data, in the writing of the report, or in the decision to submit the paper for publication.

Author information

Author notes

  1. These authors contributed equally: Yaohua Yang, Shuai Xu.

Authors and Affiliations

  1. Center for Public Health Genomics, Department of Public Health Sciences, UVA Comprehensive Cancer Center, School of Medicine, University of Virginia, Charlottesville, VA, USA

    Yaohua Yang

  2. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

    Shuai Xu, Guochong Jia, Fangcheng Yuan, Jie Ping, Xingyi Guo, Xiao-Ou Shu, Wei Zheng, Jirong Long & Qiuyin Cai

  3. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA

    Ran Tao

  4. Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA

    Ran Tao

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  1. Yaohua Yang
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Contributions

YY and QC conceived the study. YY and SX analyzed data and drafted the initial manuscript. GJ, FY, JP, XG, RT, XOS, WZ, JL, and QC contributed to the design of the study and revised the manuscript.

Corresponding authors

Correspondence to Yaohua Yang or Qiuyin Cai.

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All included datasets were approved by respective ethics/institutional review committees, in accordance with the Declaration of Helsinki.

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Yang, Y., Xu, S., Jia, G. et al. Integrating genomics and proteomics data to identify candidate plasma biomarkers for lung cancer risk among European descendants. Br J Cancer 129, 1510–1515 (2023). https://doi.org/10.1038/s41416-023-02419-3

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