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

2020 ◽  
Vol 57 (3) ◽  
pp. 11-16
Author(s):  
T. G. GONCHAROVA ◽  
D. R. KAIDAROVA ◽  
R. E. KADYRBAYEVA ◽  
M. G. ORAZGALIEVA ◽  
D. G. ADILBAY ◽  
...  

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.

2020 ◽  
Vol 10 ◽  
Author(s):  
Juanhong Shi ◽  
Xue Chen ◽  
Long Zhang ◽  
Xia Fang ◽  
Yuting Liu ◽  
...  

Emerging molecular diagnostic methods are more sensitive and objective, which can overcome the intrinsic failings of morphological diagnosis. Here, a RT-PCR-based in vitro diagnostic test kit (LungMe®) was developed and characterized to simultaneously quantify the DNA methylation of SHOX2 and RASSF1A in FFPE tissue specimens. The clinical manifestations were evaluated in 251 FFPE samples with specificity and sensitivity of 90.4 and 89.8%, respectively. Furthermore, the quantitative analysis shows that the degree of SHOX2 methylation was correlated with the stages of lung cancer, but not in the case of RASSF1A. Our observation indicated that the DNA methylation of SHOX2 and RASSF1A may play different roles in cancer development. Comparison of the methylation levels of SHOX2 and RASSF1A between cancer and cancer-adjacent specimens (n = 30), showed they have “epigenetic field defect”. As additional clinical validation, the hypermethylation of SHOX2 and RASSF1A was detected not only in surgical operative specimens, but also in histopathological negative puncture biopsies. SHOX2 and RASSF1A methylation detection can be used to increase sensitivity and NPV, which provide us with a more accurate method of differential diagnosis and are likely to be rapidly applied in clinical examinations.


Epigenetics ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. 1504-1510 ◽  
Author(s):  
Lissette Delgado-Cruzata ◽  
Neomi Vin-Raviv ◽  
Parisa Tehranifar ◽  
Julie Flom ◽  
Diane Reynolds ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Slawomir Michalak ◽  
Joanna Rybacka-Mossakowska ◽  
Wojciech Ambrosius ◽  
Joanna Gazdulska ◽  
Iwona Gołda-Gocka ◽  
...  

Objective. To evaluate the involvement of glutamate metabolism in peripheral blood mononuclear cells (PBMC) in the development of neurological complications in lung cancer and during chemotherapy. Methods. The prospective study included 221 lung cancer patients treated with chemotherapeutics. Neurological status and cognitive functions were evaluated at baseline and after 6-month follow-up. Glutamate level, the activities of glutaminase- (GLS-) glutamate synthetizing enzyme, glutamate dehydrogenase (GDH), and glutamate decarboxylase catalyzing glutamate degradation were analyzed in PBMC and in sera of lung cancer patients by means of spectrophotometric and colorimetric methods. Results. Chemotherapy of lung neoplasms induced increase of glutamate content in PBMC and its concentration in serum increased the activity of GDH in PBMC and decreased activity of glutaminase in PBMC. The changes in glutamate metabolism markers were associated with initial manifestation of neurological deficit in lung cancer patients and with new symptoms, which appear as a complication of chemotherapy. Moreover, the analyzed parameters of glutamate control correlated with a spectrum of cognitive functions measures in lung cancer patients. Conclusion. We have demonstrated dysregulation in glutamate and glutamate metabolism controlling enzymes as promising indicators of risk for chemotherapy-induced neurological complications in lung cancer patients with particular emphasis on cognitive impairment.


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