Department of Anatomy and BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 2-101 Dongin-dong, Jung-gu, Daegu, 702-422, Republic of Korea.
Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, 702-422, Republic of Korea.
Genes Genomics. 2020 May;42(5):571-579. doi: 10.1007/s13258-020-00925-9. Epub 2020 Mar 21.
Non-small cell lung cancer (NSCLC) poses a great threat to human health. DNA methylation abnormalities play a central role in the development and outcome of most human malignancies, providing potential biomarkers for diagnosis and prognosis. Iroquois homeobox 1 (IRX1) can act as a tumor suppressor or promoter depending on the tumor microenvironment, and its role in lung cancer is still controversial.
The purpose of this study was to investigate the biological role and prognostic value of IRX1 in NSCLC.
We examined the methylation status of IRX1 promoter in 146 tumors from patients with NSCLC using pyrosequencing and analyzed the association between methylation status and overall patient survival.
A total of 37 cases (25.3%) showed IRX1 methylation-positive tumors when compared with matched normal tissues. No association between IRX1 expression level and methylation status was found in lung cancer cell lines. IRX1 methylation significantly correlated with smoking status and TP53 mutation. Patients with IRX1 methylation showed significantly longer survival than patients without methylation (log-rank P = 0.011). In a multivariate analysis of prognostic factors, IRX1 methylation in tumor samples was an independent prognostic factor (adjusted hazard ratio = 0.35, 95% confidence interval 0.17-0.73, P = 0.005).
These results suggest that IRX1 promoter methylation may be a tumor-associated event and an independent predictor of survival advantage in patients with NSCLC. Further large-scale studies are needed to confirm these findings.
非小细胞肺癌（NSCLC）对人类健康构成了巨大威胁。DNA 甲基化异常在大多数人类恶性肿瘤的发生和转归中起着核心作用，为诊断和预后提供了潜在的生物标志物。同源异形盒基因 1（IRX1）可以根据肿瘤微环境发挥肿瘤抑制因子或促进因子的作用，其在肺癌中的作用仍存在争议。
本研究旨在探讨 IRX1 在 NSCLC 中的生物学作用和预后价值。
我们使用焦磷酸测序检测了 146 例 NSCLC 患者肿瘤组织中 IRX1 启动子的甲基化状态，并分析了甲基化状态与总患者生存的相关性。
与匹配的正常组织相比，共有 37 例（25.3%）显示 IRX1 甲基化阳性肿瘤。在肺癌细胞系中未发现 IRX1 表达水平与甲基化状态之间存在关联。IRX1 甲基化与吸烟状态和 TP53 突变显著相关。IRX1 甲基化的患者生存时间明显长于无甲基化的患者（对数秩 P=0.011）。在对预后因素的多因素分析中，肿瘤样本中的 IRX1 甲基化是独立的预后因素（调整后的危险比=0.35，95%置信区间 0.17-0.73，P=0.005）。
这些结果表明，IRX1 启动子甲基化可能是一种与肿瘤相关的事件，并且是 NSCLC 患者生存优势的独立预测因子。需要进一步的大规模研究来证实这些发现。
