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

Corresponding author: TanNianxi, tannianxi1981@163.com

DOI: 10.12201/bmr.202510.00045

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  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

  Submit time: 25 October 2025

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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