**Yujin Kim 1, Bo Bin Lee 1, Dongho Kim 1, Sangwon Um 2, Eun Yoon Cho 3, Joungho Han 3, Young Mog Shim <sup>4</sup> and Duk-Hwan Kim 1,\***


Received: 3 May 2020; Accepted: 27 May 2020; Published: 2 June 2020

**Abstract:** This study aimed to understand the clinicopathological significance of runt-related transcription factor 1 (*RUNX1*) in non-small cell lung cancer (NSCLC). The methylation and mRNA levels of *RUNX1* in NSCLC were determined using the Infinium HumanMethylation450 BeadChip and the HumanHT-12 expression BeadChip. RUNX1 protein levels were analyzed using immunohistochemistry of formalin-fixed paraffin-embedded tissues from 409 NSCLC patients. Three CpGs (cg04228935, cg11498607, and cg05000748) in the CpG island of *RUNX1* showed significantly different methylation levels (Bonferroni corrected *p* < 0.05) between tumor and matched normal tissues obtained from 42 NSCLC patients. Methylation levels of the CpGs in the tumor tissues were inversely related to mRNA levels of *RUNX1*. A logistic regression model based on cg04228935 showed the best performance in predicting NSCLCs in a test dataset (N = 28) with the area under the receiver operating characteristic (ROC) curve (AUC) of 0.96 (95% confidence interval (CI) = 0.81–0.99). The expression of RUNX1 was reduced in 125 (31%) of 409 patients. Adenocarcinoma patients with reduced RUNX1 expression showed 1.97-fold (95% confidence interval = 1.16–3.44, *p* = 0.01) higher hazard ratio for death than those without. In conclusion, the present study suggests that abnormal methylation of *RUNX1* may be a valuable biomarker for detection of NSCLC regardless of race. And, reduced RUNX1 expression may be a prognostic indicator of poor overall survival in lung adenocarcinoma.

**Keywords:** lung cancer; RUNX1; methylation; biomarker; survival
