Association between the methylations of RUNX3 in peripheral blood and lung cancer: a case-control study

Abstract

Background

RUNX3 is hypermethylated in multiple cancers. TIMP2 also functions as a regulator of tumors. However, there are only very few reports on the association of methylation of RUNX3 and TIMP2 with lung cancer (LC) in peripheral blood.

Methods

426 LC patients and 428 age- and sex-matched healthy controls were recruited. DNA methylation in blood was semi-quantitively assessed by mass spectrometry. For the association analysis, binary logistic regression analysis adjusted covariant was applied, and ORs were presented as per +10% methylation.

Results

Hypermethylation of CpG_1, CpG_5 and CpG_8 in RUNX3 was significantly associated with LC (ORs = 1.45, 1.35 and 1.35, respectively, adjusted p < 0.05), and even stage I LC. The association between the three RUNX3 CpG sites and LC was enhanced by increased age (> 55 years, ORs ranged from 1.43 to 1.75, adjusted p < 0.05), male gender (ORs ranged from 1.47 to 1.59, adjusted p < 0.05) and tumor stage (stage II&III&IV, ORs ranged from 1.86 to 3.03, adjusted p < 0.05).

Conclusions

This study suggests a significant association between blood-based RUNX3 hypermethylation and LC, especially in elder people, in males and in LC patients with advanced stage.

Clinical significance

• The blood-based RUNX3 hypermethylation is associated with LC, especially stage I LC.

• LC-associated blood RUNX3 hypermethylation is increased with age.

• More LC-associated RUNX3 hypermethylation are found in males.

Graphical Abstract

Keywords:

• Lung cancer
• peripheral blood
• RUNX3
• methylation
• mass spectrometry

Acknowledgments

Thank all the study participants for their contribution to the project.

Authors’ contributions

Rongxi Yang and Wanjian Gu conceived the study concept and design. Jie Zhang, Haixia Gong, Jinchang Li, Yuyang Huang and Boyue Ma enrolled the patients, collected and captured the clinical data, and classified the study participants. Jun Wang completed the experiments. Yakang Song performed the data analysis. Jun Wang and Jue Wang drafted the manuscript. Rongxi Yang reviewed and edited the manuscript. All authors read and approved the final draft.

Disclosure statement

No potential conflict of interest was reported by author(s).

Ethical approval and consent to participate

This study was approved by the ethnic committee of the respective hospitals and in accordance with the Declaration of Helsinki. Written informed consent was obtained from each subject.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the Nanjing Social Supporting Department and Social Supporting Ministry of Jiangsu Province granted from 2018 to 2020, and was supported by the Nanjing TANTICA Co. Ltd under Grant [number 2018LC01.1].