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.
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.