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

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:

• lung cancer
• DNA methylation
• peripheral blood
• biomarker

Acknowledgments

We are grateful to Feifei Di, Jin Zhang and Jiao Yang from Nanjing TANTICA Biotechnology Co. Ltd for their contribution to the sample processing.

Ethics Approval and Informed Consent

The present study was approved by the Ethics Committee of the Shanghai Chest Hospital and Jiangsu Province Hospital of Chinese Medicine in China. Written informed consents were obtained from all the participants.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.