The Association Between PNPLA2 Methylation in Peripheral Blood and Early-Stage Lung Cancer in a Case-Control Study

Rong Qiao; Mengxia Li; Runbo Zhong; Yujie Wei; Jun Wang; Zheng Zhang; Ling Wang; Tian Xu; Yue Wang; Liping Dai; Wanjian Gu; Baohui Han; Rongxi Yang

doi:10.2147/CMAR.S329629

The Association Between PNPLA2 Methylation in Peripheral Blood and Early-Stage Lung Cancer in a Case-Control Study

Cancer Manag Res. 2021 Oct 15:13:7919-7927. doi: 10.2147/CMAR.S329629. eCollection 2021.

Authors

Rong Qiao^#¹, Mengxia Li^#², Runbo Zhong¹, Yujie Wei³, Jun Wang³, Zheng Zhang³, Ling Wang³, Tian Xu⁴, Yue Wang¹, Liping Dai⁵, Wanjian Gu⁴, Baohui Han¹, Rongxi Yang^{2

3}

Affiliations

¹ Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, People's Republic of China.
² Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 210000, People's Republic of China.
³ Nanjing TANTICA Biotechnology Co. Ltd, Nanjing, 210000, People's Republic of China.
⁴ Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210000, People's Republic of China.
⁵ Henan Institute of Medical and Pharmaceutical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450052, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Lung cancer (LC) brings great burden to the society worldwide. Exploring novel biomarkers in vitro for the early detection of LC would be of great importance.

Patients and methods: We measured DNA methylation levels of 21 CpG sites within Patatin-like phospholipase domain containing 2 (PNPLA2) gene in the peripheral blood of 168 early-stage LC cases (94.0% LC at stage I) and 187 age- and gender-matched cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression adjusted for covariates. Non-parametric tests were applied for the comparisons of stratified groups.

Results: Hypomethylation of PNPLA2_CpG_8,10 and hypermethylation of PNPLA2_CpG_9 were correlated to the early-stage LC with the ORs of 1.44 (95% CI: 1.06-1.96, P = 0.018) and 0.82 (95% CI: 0.69-0.98, P = 0.029), respectively. The associations were still significant for the very early-stage LC patients (stage I). Further gender- and age-stratified analyses indicated that the association between hypomethylation of PNPLA2_CpG_8,10 and LC existed only in females and in subjects younger than 55 years. In addition, the association between LC and hypermethylation of PNPLA2_CpG_6 and PNPLA2_CpG_9 was also observed in the younger population.

Conclusion: Taken together, our study has proved the hypothesis that the altered methylation in the peripheral blood may be correlated with the burden of cancer at an early stage. Here, we find a novel association between blood-based aberrant PNPLA2 methylation and LC at a very early stage and particularly for women at a younger age.

Keywords: DNA methylation; biomarker; lung cancer; peripheral blood.

Grants and funding

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.