Assessment of the Prognostic Value of Methylation Status and Expression Levels of FHIT, GSTP1 and p16 in Non-Small Cell Lung Cancer in Egyptian Patients

Haroun, Riham Abdel-Hamid; Zakhary, Nadia Iskandar; Mohamed, Mohamed Ragaa; Abdelrahman, Abdelrahman Mohamed; Kandil, Eman Ibrahim; Shalaby, Kamal Ali

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자료유형: 학술저널

저자정보: Haroun, Riham Abdel-Hamid (Department of Biochemistry, Faculty of Science, Ain Shams University) Zakhary, Nadia Iskandar (Department of Cancer Biology, National Cancer Institute, Cairo University) Mohamed, Mohamed Ragaa (Department of Biochemistry, Faculty of Science, Ain Shams University) Abdelrahman, Abdelrahman Mohamed (Department of Surgical Oncology, National Cancer Institute, Cairo University) Kandil, Eman Ibrahim (Department of Biochemistry, Faculty of Science, Ain Shams University) Shalaby, Kamal Ali (Department of Biochemistry, Faculty of Science, Ain Shams University)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제15권 제10호

발행연도: 2014.1

수록면: 4,281 - 4,287 (7page)

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Background: Methylation of tumor suppressor genes has been investigated in all kinds of cancer. Tumor specific epigenetic alterations can be used as a molecular markers of malignancy, which can lead to better diagnosis, prognosis and therapy. Therefore, the aim of this study was to evaluate the association between gene hypermethylation and expression of fragile histidine triad (FHIT), glutathione S-transferase P1 (GSTP1) and p16 genes and various clinicopathologic characteristics in primary non-small cell lung carcinomas (NSCLC). Materials and Methods: The study included 28 primary non-small cell lung carcinomas, where an additional 28 tissue samples taken from apparently normal safety margin surrounding the tumors served as controls. Methylation-specific polymerase chain reaction (MSP) was performed to analyze the methylation status of FHIT, GSTP1 and p16 while their mRNA expression levels were measured using a real-time PCR assay with SYBR Green I. Results: The methylation frequencies of the genes tested in NSCLC specimens were 53.6% for FHIT, 25% for GSTP1, and 0% for p16, and the risk of FHIT hypermethylation increased among patients with NSCLC by 2.88, while the risk of GSTP1 hypermethylation increased by 2.33. Hypermethylation of FHIT gene showed a highly significant correlation with pathologic stage (p<0.01) and a significant correlation with smoking habit and FHIT mRNA expression level (p<0.05). In contrast, no correlation was observed between the methylation of GSTP1 or p16 and smoking habit or any other parameter investigated (p>0.05). Conclusions: Results of the present study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC. FHIT methylation may play a role in lung cancer later metastatic stages while GSTP1 methylation may rather play a role in the early pathogenesis.

#Fragile histidine triad #glutathione S-transferase P1 #p16 #promoter methylation

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