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<p>Squamous cell lung carcinoma (SCLC) accounts for approximately 30% of lung cancer cases and arises from progressive pathological changes in the bronchial epithelium including basal cell hyperplasia (BCH), squamous metaplasia (SM), and dysplasia. These changes are linked to chronic inflammation. This inflammation can lead to chronic obstructive pulmonary disease (COPD), which in turn is associated with 10–30% of lung cancer-related deaths among patients. One of the relevant problems is the unavailability of biological material from precancerous foci of the bronchial epithelium of COPD patients, which can be addressed through the development of markers in the form of liquid biopsy. Methylated DNA changes can be used as molecular markers of malignancy. The purpose of present study is to justify the potential significance of three genes methylation level for assessing the risk of lung cancer development in COPD patients. The study included 56 COPD patients and 12 healthy subjects. Cell-free DNA (cfDNA) was isolated from blood plasma. We performed the target bisulfite sequencing and real-time methyl-specific PCR for analysis of cfDNA samples. We selected three marker genes whose methylation levels in the tissue increased during disease progression from squamous carcinoma to dysplasia and then to tumor. These marker genes were identified during previously conducted whole genome-sequencing (retrospective study). CfDNA from blood plasma of COPD patients and healthy subjects was used for <i>RARB, ZNF260,</i> and <i>DCDC1</i> genes methylation level detection. Hypermethylation of 3 CpG and 2 CpG sites for the <i>RARB</i> and <i>ZNF260</i> genes was shown in COPD patients when compared with healthy subjects (<i>P</i> ≤ 0.05). Eight COPD patients (14% cases) were diagnosed with lung cancer during post-treatment monitoring. Hypermethylation of the <i>RARB2</i> and/or <i>ZNF260</i> genes in cfDNA was detected in these patients before the clinical diagnostics was made. The data obtained indicate the potential significance of the analysis of circulating <i>RARB2, ZNF260,</i> and <i>DCDC1</i> genes methylation for assessing the risk of LC development in patients with COPD.</p>

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Circulating Methylated DNA as Biomarkers of High Lung Cancer Risk in COPD Patients

  • 期刊论文

  • 发表日期：

    2026年7月22日

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  • Anastasia Ponomaryova,
  • Valentina Boyarko,
  • Daria Kapitanova,
  • Ekaterina Bukreeva,
  • Aleksei Zarubin,
  • Elena Rykova,
  • Vladimir Perelmuter,
  • Nadezhda Cherdyntseva,
  • Evgeniy Denisov

摘要

Squamous cell lung carcinoma (SCLC) accounts for approximately 30% of lung cancer cases and arises from progressive pathological changes in the bronchial epithelium including basal cell hyperplasia (BCH), squamous metaplasia (SM), and dysplasia. These changes are linked to chronic inflammation. This inflammation can lead to chronic obstructive pulmonary disease (COPD), which in turn is associated with 10–30% of lung cancer-related deaths among patients. One of the relevant problems is the unavailability of biological material from precancerous foci of the bronchial epithelium of COPD patients, which can be addressed through the development of markers in the form of liquid biopsy. Methylated DNA changes can be used as molecular markers of malignancy. The purpose of present study is to justify the potential significance of three genes methylation level for assessing the risk of lung cancer development in COPD patients. The study included 56 COPD patients and 12 healthy subjects. Cell-free DNA (cfDNA) was isolated from blood plasma. We performed the target bisulfite sequencing and real-time methyl-specific PCR for analysis of cfDNA samples. We selected three marker genes whose methylation levels in the tissue increased during disease progression from squamous carcinoma to dysplasia and then to tumor. These marker genes were identified during previously conducted whole genome-sequencing (retrospective study). CfDNA from blood plasma of COPD patients and healthy subjects was used for RARB, ZNF260, and DCDC1 genes methylation level detection. Hypermethylation of 3 CpG and 2 CpG sites for the RARB and ZNF260 genes was shown in COPD patients when compared with healthy subjects (P ≤ 0.05). Eight COPD patients (14% cases) were diagnosed with lung cancer during post-treatment monitoring. Hypermethylation of the RARB2 and/or ZNF260 genes in cfDNA was detected in these patients before the clinical diagnostics was made. The data obtained indicate the potential significance of the analysis of circulating RARB2, ZNF260, and DCDC1 genes methylation for assessing the risk of LC development in patients with COPD.