Clinicopathological Significance of <i>RUNX1</i> in Non-Small Cell Lung Cancer

초록

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 ofRUNX1in 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 ofRUNX1showed significantly different methylation levels (Bonferroni correctedp< 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 ofRUNX1. 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 ofRUNX1may 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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