Early diagnostic of lung cancer based on methylation of mononuclear cell fraction: Method development

Abstract

Relevance: According to the International Agency for Research on Cancer (IARС), lung cancer (LC) today ranks first in cancer
 incidence worldwide [1]. In the Republic of Kazakhstan, about 3800 new cases of LC and more than 2000 deaths from LC are
 registered each year (one-year mortality exceeds 49.4%) [2]. This supports the relevance of early LC diagnostics. The study of
 DNA methylation in human peripheral blood mononuclear cells (PBMC) suggests its use as an early diagnostic and prognostic
 marker for LC before detecting a malignant neoplasm by visual diagnostic methods.
 The purpose of the study was to find specific diagnostic and prognostic markers by DNA methylation profiling of PBMC
 in patients with LC.
 Results: Methylation markers of blood mononuclear fraction were detected in CG islets associated with genes ICAM5,
 mir138, SYNE1, and KLK4 in 97% of plasma samples from patients with LC and were absent in healthy people. The usability of
 these markers to differentiate LC from 16 other cancers using NCBI GEO and TCGA methylation data was demonstrated with a
 specificity level of 0.96 and a sensitivity of 0.84.
 Conclusion: The specificity and sensitivity of the method of LC early diagnostics and prognosis based on the methylation of
 blood mononuclear cells (detection of methylation of CG islets associated with the ICAM5, mir138, SYNE1, and KLK4 genes in
 PBMC) are enough to use it in screening for LC.