Evaluation of Promoter Hypermethylation of Tumor-Suppressor Genes p14 and p16 in Iranian Endometrial Carcinoma Patients
Background: Endometrial cancer is a common gynecological malignancy with good prognosis in the early stages of the disease. The CpG island in the promoter region of tumor-suppressor genes are frequently methylated in various types of human cancers. In the present study, we have examined the methy...
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Format: | Article |
Language: | English |
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Shiraz University of Medical Sciences
2017-09-01
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Series: | Middle East Journal of Cancer |
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Online Access: | http://mejc.sums.ac.ir/index.php/mejc/article/view/727/322 |
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author | Mina Azizi Golnaz Asaadi Tehrani |
author_facet | Mina Azizi Golnaz Asaadi Tehrani |
author_sort | Mina Azizi |
collection | DOAJ |
description | Background: Endometrial cancer is a common gynecological malignancy with good
prognosis in the early stages of the disease. The CpG island in the promoter region of
tumor-suppressor genes are frequently methylated in various types of human cancers.
In the present study, we have examined the methylation status of the p16INK4a and
p14ARF genes in endometrial cancer and healthy endometrium with the aim to identify
correlations between promoter hypermethylation, disease risk, and clinicopathological
parameters.
Methods: We collected 28 formalin fixed paraffin embedded samples and 26
blood samples from endometrial cancer patients and 22 controls. Methylation-specific
PCR was applied to analyze the promoter methylation status of the p16INK4a and
p14ARF genes in the studied population. The results were analyzed with SPSS software
version 20.
Results: There was a significant difference between the study groups and the
presence of promoter CpG hypermethylation status in the p14 (P<0.0001) and p16
(P<0.05) genes. p14 hypermethylation in the blood samples was associated with depth
of myometrial invasion in endometrial cancer (P=0.03). A significant association
existed between p16methylation in tissue with endometrial cancer grade (P=0.06). No
statistically significant difference existed between the p16INK4a and p14ARF promoter
hypermethylations in blood (P=0.177) and formalin fixed paraffin embedded (P=0.221)
samples. An association existed between p16INK4a and p14ARF gene hypermethylations
in blood and tissue with diabetes.
Conclusion: Our results have confirmed that epigenetic mechanisms play an
important role in endometrial cancer incidence. They can be utilized as prognostic
biomarkers for endometrial cancer. The lack of a significant difference between the
p16INK4a and p14ARF promoter hypermethylations in blood and formalin fixed
paraffin embedded samples has indicated that methylation status of a blood sample can
be an early, non-invasive diagnostic marker in endometrial cancer. |
first_indexed | 2024-12-11T10:31:13Z |
format | Article |
id | doaj.art-8f5c6020304b4a2289a94c2db5ba1ada |
institution | Directory Open Access Journal |
issn | 2008-6709 2008-6687 |
language | English |
last_indexed | 2024-12-11T10:31:13Z |
publishDate | 2017-09-01 |
publisher | Shiraz University of Medical Sciences |
record_format | Article |
series | Middle East Journal of Cancer |
spelling | doaj.art-8f5c6020304b4a2289a94c2db5ba1ada2022-12-22T01:10:55ZengShiraz University of Medical SciencesMiddle East Journal of Cancer2008-67092008-66872017-09-0184179186Evaluation of Promoter Hypermethylation of Tumor-Suppressor Genes p14 and p16 in Iranian Endometrial Carcinoma PatientsMina Azizi0Golnaz Asaadi Tehrani1Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, IranDepartment of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, IranBackground: Endometrial cancer is a common gynecological malignancy with good prognosis in the early stages of the disease. The CpG island in the promoter region of tumor-suppressor genes are frequently methylated in various types of human cancers. In the present study, we have examined the methylation status of the p16INK4a and p14ARF genes in endometrial cancer and healthy endometrium with the aim to identify correlations between promoter hypermethylation, disease risk, and clinicopathological parameters. Methods: We collected 28 formalin fixed paraffin embedded samples and 26 blood samples from endometrial cancer patients and 22 controls. Methylation-specific PCR was applied to analyze the promoter methylation status of the p16INK4a and p14ARF genes in the studied population. The results were analyzed with SPSS software version 20. Results: There was a significant difference between the study groups and the presence of promoter CpG hypermethylation status in the p14 (P<0.0001) and p16 (P<0.05) genes. p14 hypermethylation in the blood samples was associated with depth of myometrial invasion in endometrial cancer (P=0.03). A significant association existed between p16methylation in tissue with endometrial cancer grade (P=0.06). No statistically significant difference existed between the p16INK4a and p14ARF promoter hypermethylations in blood (P=0.177) and formalin fixed paraffin embedded (P=0.221) samples. An association existed between p16INK4a and p14ARF gene hypermethylations in blood and tissue with diabetes. Conclusion: Our results have confirmed that epigenetic mechanisms play an important role in endometrial cancer incidence. They can be utilized as prognostic biomarkers for endometrial cancer. The lack of a significant difference between the p16INK4a and p14ARF promoter hypermethylations in blood and formalin fixed paraffin embedded samples has indicated that methylation status of a blood sample can be an early, non-invasive diagnostic marker in endometrial cancer.http://mejc.sums.ac.ir/index.php/mejc/article/view/727/322Endometrial cancerEpigeneticp14ARFp16INK4a |
spellingShingle | Mina Azizi Golnaz Asaadi Tehrani Evaluation of Promoter Hypermethylation of Tumor-Suppressor Genes p14 and p16 in Iranian Endometrial Carcinoma Patients Middle East Journal of Cancer Endometrial cancer Epigenetic p14ARF p16INK4a |
title | Evaluation of Promoter Hypermethylation of Tumor-Suppressor Genes p14 and p16 in Iranian Endometrial Carcinoma Patients |
title_full | Evaluation of Promoter Hypermethylation of Tumor-Suppressor Genes p14 and p16 in Iranian Endometrial Carcinoma Patients |
title_fullStr | Evaluation of Promoter Hypermethylation of Tumor-Suppressor Genes p14 and p16 in Iranian Endometrial Carcinoma Patients |
title_full_unstemmed | Evaluation of Promoter Hypermethylation of Tumor-Suppressor Genes p14 and p16 in Iranian Endometrial Carcinoma Patients |
title_short | Evaluation of Promoter Hypermethylation of Tumor-Suppressor Genes p14 and p16 in Iranian Endometrial Carcinoma Patients |
title_sort | evaluation of promoter hypermethylation of tumor suppressor genes p14 and p16 in iranian endometrial carcinoma patients |
topic | Endometrial cancer Epigenetic p14ARF p16INK4a |
url | http://mejc.sums.ac.ir/index.php/mejc/article/view/727/322 |
work_keys_str_mv | AT minaazizi evaluationofpromoterhypermethylationoftumorsuppressorgenesp14andp16iniranianendometrialcarcinomapatients AT golnazasaaditehrani evaluationofpromoterhypermethylationoftumorsuppressorgenesp14andp16iniranianendometrialcarcinomapatients |