Summary: | This study aimed to understand the clinicopathological significance of runt-related transcription factor 1 (<i>RUNX1</i>) in non-small cell lung cancer (NSCLC). The methylation and mRNA levels of <i>RUNX1</i> 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 <i>RUNX1</i> showed significantly different methylation levels (Bonferroni corrected <i>p</i> < 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 <i>RUNX1</i>. 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, <i>p</i> = 0.01) higher hazard ratio for death than those without. In conclusion, the present study suggests that abnormal methylation of <i>RUNX1</i> 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.
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