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The Association Between RAPSN Methylation in Peripheral Blood and Early Stage Lung Cancer Detected in Case–Control Cohort

Authors Qiao R, Di F, Wang J, Wei Y, Zhang Y, Xu T, Wang Y, Gu W, Han B, Yang R

Received 3 August 2020

Accepted for publication 3 October 2020

Published 2 November 2020 Volume 2020:12 Pages 11063—11075

DOI https://doi.org/10.2147/CMAR.S275321

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo


Rong Qiao,1,* Feifei Di,2,* Jun Wang,2 Yujie Wei,2 Yanman Zhang,2 Tian Xu,3 Yue Wang,1 Wanjian Gu,3 Baohui Han,1 Rongxi Yang2,4

1Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, People’s Republic of China; 2Department of Research and Academic, Nanjing TANTICA Biotechnology Co. Ltd, Nanjing 210000, People’s Republic of China; 3Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210000, People’s Republic of China; 4Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Rongxi Yang; Baohui Han Email rongxiyang@njmu.edu.cn; 18930858216@163.com

Background: Early detection is essential to improve the survival and life quality of lung cancer (LC) patients. Changes of peripheral blood DNA methylation could be associated with malignancy but were mostly studied in Caucasians.
Methods: Here, in a Chinese population, we performed mass spectrometry assays to investigate the association between very early stage LC and methylation levels of RAPSN in the peripheral blood by a case–control cohort using of 221 LC patients (93.2% LC at stage I) and 285 unrelated cancer free control individuals.
Results: The odds ratios (ORs) of all CpG sites were evaluated for their risk to LC using inter-quartile analyses by logistic regression. In general, we observed an association between very early LC and decreased methylation of RAPSN_CpG_1.15 and RAPSN_CpG_3.4 (referring to Q4, OR range from 1.64 to 1.81, p< 0.05). Stratified by gender, while hypomethylation of RAPSN_CpG_1.15, RAPSN_CpG_3.4 and RAPSN_CpG_7.14 were associated with LC in males (referring to Q4, ORs range from 1.94 to 2.31, p< 0.05), RAPSN_CpG_2 and RAPSN_CpG_5 showed significantly lower methylation in female LC patients comparing to controls (referring to Q4, ORs range from 2.49 to 3.60, p< 0.05). The risk of RAPSN hypomethylation to LC was enhanced by aging, and typically for people older than 55 years (referring to Q4, ORs range from 2.17 to 3.61 in six out of all 10 analyzed CpG groups, p< 0.05).
Conclusion: Our study reveals an association between RAPSN hypomethylation in peripheral blood and LC and suggests the occurrence of altered blood-based methylation at the early stage of cancer.

Keywords: LC, early detection, DNA methylation, RAPSN, peripheral blood

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