Kim Yujin, Lee Bo Bin, Kim Dongho, Um Sangwon, Cho Eun Yoon, Han Joungho, Shim Young Mog, Kim Duk-Hwan
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
J Clin Med. 2020 Jun 2;9(6):1694. doi: 10.3390/jcm9061694.
This study aimed to understand the clinicopathological significance of runt-related transcription factor 1 () in non-small cell lung cancer (NSCLC). The methylation and mRNA levels of 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 showed significantly different methylation levels (Bonferroni corrected < 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 . 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, = 0.01) higher hazard ratio for death than those without. In conclusion, the present study suggests that abnormal methylation of 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.
本研究旨在了解 runt 相关转录因子 1（RUNX1）在非小细胞肺癌（NSCLC）中的临床病理意义。使用 Infinium HumanMethylation450 芯片和 HumanHT-12 表达芯片测定 NSCLC 中 RUNX1 的甲基化和 mRNA 水平。采用免疫组织化学方法分析 409 例 NSCLC 患者福尔马林固定石蜡包埋组织中的 RUNX1 蛋白水平。在 42 例 NSCLC 患者的肿瘤组织和配对正常组织中，RUNX1 基因启动子区域的三个 CpG 位点（cg04228935、cg11498607 和 cg05000748）显示出显著不同的甲基化水平（经 Bonferroni 校正后 P < 0.05）。肿瘤组织中这些 CpG 位点的甲基化水平与 RUNX1 的 mRNA 水平呈负相关。基于 cg04228935 的逻辑回归模型在测试数据集（N = 28）中预测 NSCLC 时表现最佳，受试者工作特征（ROC）曲线下面积（AUC）为 0.96（95%置信区间（CI）= 0.81 - 0.99）。409 例患者中有 125 例（31%）RUNX1 表达降低。RUNX1 表达降低的腺癌患者死亡风险比未降低的患者高 1.97 倍（95%置信区间 = 1.16 - 3.44，P = 0.01）。总之，本研究表明，无论种族如何，RUNX1 的异常甲基化可能是检测 NSCLC 的有价值生物标志物。并且，RUNX1 表达降低可能是肺腺癌总体生存不良的预后指标。
