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KMID : 0381120220440040445
Genes and Genomics
2022 Volume.44 No. 4 p.445 ~ p.453
Novel blood-based hypomethylation of SH3BP5 is associated with very early-stage lung adenocarcinoma
Qiao Rong

Zhong Runbo
Liu Chunlan
Di Feifei
Zhang Zheng
Wang Ling
Xu Tian
Wang Yue
Dai Liping
Gu Wanjian
Han Baohui
Yang Rongxi
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?
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.
KEYWORD
Lung cancer, DNA methylation, SH3BP5, Early stage, Biomarker
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