Rong Qiao1, Runbo Zhong1, Chunlan Liu2, Feifei Di3, Zheng Zhang3, Ling Wang3, Tian Xu4, Yue Wang1, Liping Dai5, Wanjian Gu4, Baohui Han6, Rongxi Yang7,8. 1. Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China. 2. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 210000, China. 3. Nanjing TANTICA Biotechnology Co. Ltd, Nanjing, 210000, China. 4. Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210000, China. 5. Henan Institute of Medical and Pharmaceutical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450052, China. 6. Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China. 18930858216@163.com. 7. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 210000, China. rongxiyang@njmu.edu.cn. 8. Nanjing TANTICA Biotechnology Co. Ltd, Nanjing, 210000, China. rongxiyang@njmu.edu.cn.
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.
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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