通讯作者: 谭年喜, tannianxi1981@163.com

DOI：10.12201/bmr.202510.00045

Relationship between DNA methylation of RUNX3, P16 and DAPK gene promoters and chemosensitivity in non-small cell lung cancer

• 摘要：目的:探讨RUNX3、P16和DAPK基因启动子DNA甲基化与非小细胞肺癌(NSCLC)化疗敏感性的关系。方法:2023年2月-2025年2月间在本院接受铂类化疗的初治晚期NSCLC患者116例,治疗前经活检明确分期并获取组织标本。根据化疗效果分为敏感组(n＝81)、耐受组(n＝35),对比两组患者的病灶组织标本RUNX3、P16、DAPK基因启动子DNA甲基化情况、基因转录水平绝对定量,绘制受试者工作特征(ROC)评估RUNX3、P16、DAPK基因表达水平对后续铂类化疗耐药的预测价值。结果:耐受组患者的肺癌组织RUNX3、P16和DAPK基因启动子DNA甲基化比例高于敏感组患者,差异有统计学意义(P＜0.05)。耐受组患者的肺癌组织RUNX3、P16和DAPK基因转录水平低于敏感组患者,差异有统计学意义(P＜0.05)。ROC曲线显示,肺癌组织RUNX3 mRNA、P16 mRNA、DAPK mRNA水平预测NSCLC患者化疗敏感的最佳截断值分别为2.93×106、5.22×104、6.420×105,AUC分别为0.72695%CI 0.617~0.834、0.74895%CI 0.638~0.858、0.76395%CI 0.660~0.866,对应的灵敏度、特异度分别为69.77%、72.92%,70.27%、63.16%,64.10%、69.77%。RUNX3、P16、DAPK mRNA联合预测NSCLC患者化疗敏感的AUC为0.88395%CI 0.792~0.949,对应的灵敏度、特异度为81.82%、78.05%。三个基因联合预测的AUC及灵敏度、特异度均优于单一基因(P＜0.05)。结论:RUNX3、P16、DAPK基因甲基化可能是晚期NSCLC患者铂类化疗耐药的原因之一,早期测定此类基因转录水平可以在预估化疗耐药、个体化治疗方案明确方面具有积极作用。

  关键词： 非小细胞肺癌; DNA甲基化; 化疗敏感性; RUNX3; P16; DAPK

   

  Abstract: Objective: To explore t relationship between DNA methylation of promoters of RUNX3, P16 and DAPK genes and chemosensitivity in NSCLC. Methods: A total of 116 patients with initially treated advanced NSCLC who received platinum-based chemotherapy in our hospital from February 2023 to February 2025 were included. Before treatment, biopsy was performed to determine stage and tissue specimens were obtained. According to chemotherapy effect, patients were divided into sensitive group(n=81) and tolerant group(n=35). DNA methylation status of RUNX3, P16, and DAPK gene promoters and absolute quantification of gene transcription levels in lesion tissue specimens of two groups were compared. ROC was plotted to evaluate predictive value of expression levels of RUNX3, P16, and DAPK genes for subsequent platinum-based chemotherapy resistance. Result: Proportion of DNA methylation of RUNX3, P16 and DAPK gene promoters in lung cancer tissues of tolerance group was higher than that of sensitive group, the difference was statistically significant(P<0.05). Transcriptional levels of RUNX3, P16 and DAPK genes in lung cancer tissues of patients in the tolerance group were lower than those in sensitive group, the difference was statistically significant(P<0.05). ROC curve shows that optimal cut-off values of RUNX3 mRNA, P16 mRNA, and DAPK mRNA levels in lung cancer tissues for predicting chemotherapy sensitivity in NSCLC patients are 2.93×106, 5.22×104, and 6.420×105 respectively. AUCs were 0.72695%CI 0.617-0.834, 0.74895%CI 0.638-0.858, and 0.76395%CI 0.660-0.866 respectively, corresponding sensitivities and specificities were 69.77%、72.92%;70.27%、63.16%; 64.10%、69.77% respectively. AUC for combined prediction of chemotherapy sensitivity in NSCLC patients by RUNX3, P16, DAPK mRNA was 0.88395%CI 0.792-0.949, corresponding sensitivity and specificity were 81.82% and 78.05% respectively. AUC, sensitivity and specificity of combined prediction of three genes were all superior to those of single gene(P<0.05). Conclusion: Methylation of RUNX3, P16, and DAPK genes may be one of the reasons for platinum-based chemotherapy resistance in advanced NSCLC patients. Early determination of transcriptional levels of such genes can play a positive role in predicting chemotherapy resistance and clarifying individualized treatment plans.

  Key words: Non-small cell lung cancer; DNA methylation; Chemotherapysensitivity; RUNX3; P16; DAPK

  提交时间：2025-10-25

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• 序号	提交日期	编号	操作
  1	2025-07-21	10.12201/bmr.202510.00045V1	下载

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