Non-small cell lung cancer (NSCLC) is one of the most common human cancers. In this regard, the search for new biomarkers for detecting NSCLC at early stages is relevant, and one of these markers may be the methylation of CpG-islands of miRNA genes. The aim of this work was to study the level of methylation of promoter CpG-islands of miRNA genes as promising NSCLC markers.
A representative set of 80 paired (tumour/normal) NSCLC samples was used in the study. The analysis of methylation was carried out using the method of quantitative methyl-specific PCR. Statistical analysis of methylation levels was performed using a non-parametric Mann-Whitney U-test. The optimal marker systems were selected based on the results of the ROC analysis. Mathematical packages IBM SPSS Statistics 22 are used.
A representative set of 80 paired (tumour/normal) NSCLC samples was used in the study. The analysis of methylation was carried out using the method of quantitative methyl-specific PCR. Statistical analysis of methylation levels was performed using a non-parametric Mann-Whitney U-test. The optimal marker systems were selected based on the results of the ROC analysis. Mathematical packages IBM SPSS Statistics 22 are used. Results. The methylation status of 10 miRNA genes was studied, significant differences were established between methylation levels in tumour samples and histologically normal tissue of NSCLC patients for 8 genes: MIR-124A-1/3, MIR-125B-1, MIR-127, MIR-129-2, MIR-137, MIR-339 and MIR-375 (p‹0.001). Significant correlations were found between the methylation frequency of a number of miRNA genes and NSCLC progression: MIR-125B-1, MIR-137, MIR-124A-3 with cancer stage (p=0.001, 0.004 and 0.001, respectively) and MIR-125B-1 with metastasis (p=0.005). An effective marker system of 4 genes (MIR-125B-1, MIR-137, MIR-129-2, MIR-375) was determined by ROC analysis for the diagnosis of NSCLC at early stages with high clinical sensitivity (90%) and specificity (90 %); AUC value > 0.9.
Thus, new hypermethylated miRNA genes can be used as potential biomarkers for the early diagnosis of NSCLC.
The authors.
The study was supported by the state assignment of the Ministry of Science and Higher Education of the Russian Federation number FGFU-2022-0007.
All authors have declared no conflicts of interest.