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Novel blood-based hypomethylation of SH3BP5 is associated with very early-stage lung adenocarcinoma

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Abstract

Background

Early detection is essential to improve the survival of lung cancer (LC). The quantitative measurement of specific DNA methylation changes in the peripheral blood could provide an efficient strategy for the detection of early cancer.

Objective

We applied a candidate approach and assess the association between blood-based SH3BP5 methylation and the risk of lung adenocarcinoma (LUAD) in a case–control cohort.

Methods

The methylation level of four CpG sites in the promoter of SH3BP5 gene was quantitatively determined by mass spectrometry in 171 very early-stage LUAD patients (93.6% LUAD at stage I) and 190 age and gender-matched controls. The logistic regression and non-parametric tests were used for the statistical analyses.

Results

We observed a significant association between decreased methylation of SH3BP5_CpG_4 in the peripheral blood and increased risk of LUAD (odds ratio (OR) per-10% methylation = 1.51, P = 0.006, FDR = 0.024), and even for the LUAD at stage I (OR per-10% methylation = 1.53, P = 0.006, FDR = 0.024). Moreover, the lower quartile of SH3BP5_CpG_4 methylation was correlated with increased risk for LUAD with a P trend of 0.011. Further investigation disclosed that the hypomethylation of SH3BP5_CpG_4 was mostly associated with LUAD in younger subjects (OR per-10% methylation = 2.02, P = 0.010, age < 55 years old) and probably could be enhanced by advance stage.

Conclusion

Our study revealed an association between blood-based SH3BP5 hypomethylation and very early-stage LUAD, which provides a novel support for the blood-based methylation signatures as a potential marker for the evaluation of cancer risk.

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Acknowledgements

We are grateful to Jun Wang and Yujie Wei from Nanjing TANTICA Biotechnology Co. Ltd for their contribution to the sample processing. This work was supported by the Nanjing Social Supporting Department and Social Supporting Ministry of Jiangsu Province (Grant no. 20182020) and by the Nanjing TANTICA Co. Ltd with Grant number 2018LC01.1.

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Author notes

  1. Rong Qiao and Runbo Zhong contribute equal to this work.

Authors and Affiliations

  1. Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China

    Rong Qiao, Runbo Zhong, Yue Wang & Baohui Han

  2. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 210000, China

    Chunlan Liu & Rongxi Yang

  3. Nanjing TANTICA Biotechnology Co. Ltd, Nanjing, 210000, China

    Feifei Di, Zheng Zhang, Ling Wang & Rongxi Yang

  4. Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210000, China

    Tian Xu & Wanjian Gu

  5. Henan Institute of Medical and Pharmaceutical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450052, China

    Liping Dai

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  1. Rong Qiao
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Contributions

Material preparation, data collection and analysis were performed by CL, FD and ZZ. The first draft of the manuscript was written by RQ and RZ. Conception or design of the work, data interpretation and critical revision of the article were performed by RY and BH. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Baohui Han or Rongxi Yang.

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Rong Qiao, Runbo Zhong, Chunlan Liu, Feifei Di, Zheng Zhang, Ling Wang, Tian Xu, Yue Wang, Liping Dai, Wanjian Gu, Baohui Han and Rongxi Yang declare that they have no conflict of interest.

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Qiao, R., Zhong, R., Liu, C. et al. Novel blood-based hypomethylation of SH3BP5 is associated with very early-stage lung adenocarcinoma. Genes Genom 44, 445–453 (2022). https://doi.org/10.1007/s13258-021-01190-0

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