Comparative study of death-associated protein kinase promoter methylation between nonsquamous and squamous subtypes of nonsmall cell lung cancer

Background Lung cancer is a leading cause of cancer-related mortality in the world. Nonsmall cell lung cancer (NSCLC) can be classified as nonsquamous cell carcinoma (non-SCC) and squamous cell carcinoma (SCC). NSCLC pathogenesis includes altered methylation patterns in multiple genes. Promotor meth...

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Main Authors: Fatma A Hisham, Asem A Hewidy, Ahmed M Fouda, Ahmed M Abumossalam, Manal Elmasry, Manal M El-Desoky
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2021-01-01
Series:Egyptian Journal of Chest Disease and Tuberculosis
Subjects:
Online Access:http://www.ejcdt.eg.net/article.asp?issn=0422-7638;year=2021;volume=70;issue=4;spage=509;epage=515;aulast=Hisham
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author Fatma A Hisham
Asem A Hewidy
Ahmed M Fouda
Ahmed M Abumossalam
Manal Elmasry
Manal M El-Desoky
author_facet Fatma A Hisham
Asem A Hewidy
Ahmed M Fouda
Ahmed M Abumossalam
Manal Elmasry
Manal M El-Desoky
author_sort Fatma A Hisham
collection DOAJ
description Background Lung cancer is a leading cause of cancer-related mortality in the world. Nonsmall cell lung cancer (NSCLC) can be classified as nonsquamous cell carcinoma (non-SCC) and squamous cell carcinoma (SCC). NSCLC pathogenesis includes altered methylation patterns in multiple genes. Promotor methylation of death-associated protein kinase (DAPK) has been documented in various tumors. Aim To compare DAPK promoter methylation and clinical characteristics in patients of nonsquamous cell lung cancer with those of SCC. Patients and methods A case–control study was conducted on fresh-frozen tumor samples from 81 patients with primary NSCLC, including 43 non-SCC cases and 38 SCC cases, investigated in the Chest Department, Mansoura University Hospital, in the period from June 2017 to January 2020. A total of 40 patients matched for age and sex with nonmalignant lung lesions served as controls. Patients with age more than 18 years, radiological suggestions of lung cancer, and histologically diagnosed NSCLC were included, whereas patients with malignancies other than NSCLC or unfit for bronchoscopy were excluded. A pathologist histologically examined each lung tumor to define the type and other clinical characteristics of the tumor. DNA was isolated from fresh-frozen tissues, and the detection of DNA methylation was performed using methylation-specific PCR. Results NSCLC case groups included 43 nonsquamous cells and 38 squamous cells, with a mean age of 62.89±5.5 and 64.19±5.87 years, respectively. The control group included 40 patients, with a mean age of 61.37±6.64 years. There were statistically significant differences regarding smoking status (P=0.002) and the clinical characteristics suggestive of lung cancer between both patients with NSCLC and controls, but the differences between SCC and non-SCC were not significant. The results were significantly different between the two groups concerning chest radiograph and computed tomographic finding, where the peripheral mass was significantly higher in non-SCC than SCC (P<0.001). DAPK promoter methylation was significantly higher for NSCLC (both SCC and non-SCC) as compared with controls (P≤0.001), but there was no significant difference between SCC and non-SCC groups. Conclusion Detection of the aberrant DAPK hypermethylation in tumor DNA from patients with NSCLC may provide an effective means for early auxiliary diagnosis of the malignancy but cannot distinguish between the histopathological types.
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spelling doaj.art-38ba126c5eac44f5bc85fbf7342e6f842022-12-22T03:32:22ZengWolters Kluwer Medknow PublicationsEgyptian Journal of Chest Disease and Tuberculosis0422-76382090-99502021-01-0170450951510.4103/ecdt.ecdt_13_21Comparative study of death-associated protein kinase promoter methylation between nonsquamous and squamous subtypes of nonsmall cell lung cancerFatma A HishamAsem A HewidyAhmed M FoudaAhmed M AbumossalamManal ElmasryManal M El-DesokyBackground Lung cancer is a leading cause of cancer-related mortality in the world. Nonsmall cell lung cancer (NSCLC) can be classified as nonsquamous cell carcinoma (non-SCC) and squamous cell carcinoma (SCC). NSCLC pathogenesis includes altered methylation patterns in multiple genes. Promotor methylation of death-associated protein kinase (DAPK) has been documented in various tumors. Aim To compare DAPK promoter methylation and clinical characteristics in patients of nonsquamous cell lung cancer with those of SCC. Patients and methods A case–control study was conducted on fresh-frozen tumor samples from 81 patients with primary NSCLC, including 43 non-SCC cases and 38 SCC cases, investigated in the Chest Department, Mansoura University Hospital, in the period from June 2017 to January 2020. A total of 40 patients matched for age and sex with nonmalignant lung lesions served as controls. Patients with age more than 18 years, radiological suggestions of lung cancer, and histologically diagnosed NSCLC were included, whereas patients with malignancies other than NSCLC or unfit for bronchoscopy were excluded. A pathologist histologically examined each lung tumor to define the type and other clinical characteristics of the tumor. DNA was isolated from fresh-frozen tissues, and the detection of DNA methylation was performed using methylation-specific PCR. Results NSCLC case groups included 43 nonsquamous cells and 38 squamous cells, with a mean age of 62.89±5.5 and 64.19±5.87 years, respectively. The control group included 40 patients, with a mean age of 61.37±6.64 years. There were statistically significant differences regarding smoking status (P=0.002) and the clinical characteristics suggestive of lung cancer between both patients with NSCLC and controls, but the differences between SCC and non-SCC were not significant. The results were significantly different between the two groups concerning chest radiograph and computed tomographic finding, where the peripheral mass was significantly higher in non-SCC than SCC (P<0.001). DAPK promoter methylation was significantly higher for NSCLC (both SCC and non-SCC) as compared with controls (P≤0.001), but there was no significant difference between SCC and non-SCC groups. Conclusion Detection of the aberrant DAPK hypermethylation in tumor DNA from patients with NSCLC may provide an effective means for early auxiliary diagnosis of the malignancy but cannot distinguish between the histopathological types.http://www.ejcdt.eg.net/article.asp?issn=0422-7638;year=2021;volume=70;issue=4;spage=509;epage=515;aulast=Hishamdeath-associated protein kinasemethylationnonsmall cell lung cancersquamous cell lung cancer
spellingShingle Fatma A Hisham
Asem A Hewidy
Ahmed M Fouda
Ahmed M Abumossalam
Manal Elmasry
Manal M El-Desoky
Comparative study of death-associated protein kinase promoter methylation between nonsquamous and squamous subtypes of nonsmall cell lung cancer
Egyptian Journal of Chest Disease and Tuberculosis
death-associated protein kinase
methylation
nonsmall cell lung cancer
squamous cell lung cancer
title Comparative study of death-associated protein kinase promoter methylation between nonsquamous and squamous subtypes of nonsmall cell lung cancer
title_full Comparative study of death-associated protein kinase promoter methylation between nonsquamous and squamous subtypes of nonsmall cell lung cancer
title_fullStr Comparative study of death-associated protein kinase promoter methylation between nonsquamous and squamous subtypes of nonsmall cell lung cancer
title_full_unstemmed Comparative study of death-associated protein kinase promoter methylation between nonsquamous and squamous subtypes of nonsmall cell lung cancer
title_short Comparative study of death-associated protein kinase promoter methylation between nonsquamous and squamous subtypes of nonsmall cell lung cancer
title_sort comparative study of death associated protein kinase promoter methylation between nonsquamous and squamous subtypes of nonsmall cell lung cancer
topic death-associated protein kinase
methylation
nonsmall cell lung cancer
squamous cell lung cancer
url http://www.ejcdt.eg.net/article.asp?issn=0422-7638;year=2021;volume=70;issue=4;spage=509;epage=515;aulast=Hisham
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