Promoter methylation levels of RASSF1 and ATIC genes are associated with lung cancer in Iranian patients.

IF 1.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mahsa Mashayekhi, Milad Asadi, Shahriar Hashemzadeh, Amir Vahedi, Dariush Shanehbandi, Ahmad Faris Al-Omar, Morteza Akbari, Mortaza Raeisi
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引用次数: 0

Abstract

Objectives: Epigenetic alterations like methylation of tumor suppressor genes or oncogenes, in respiratory epithelium have been associated with lung cancer. Hypermethylation of genes promoter is an epigenetic event, and is responsible to tumor suppressor genes inactivation as well as oncogenes activation. This study aimed to assess the role of methylation status in promoter of RASSF1 and ATIC genes their potential implication in the pathogenesis of lung tumor in Iranian patients.

Methods: In this study, we collected 100 tissue samples (50 lung cancer tissues and 50 adjacent non-cancerous lung tissues) from Iranian lung cancer patients. The genomic DNA was extracted, and methylation status of both RASSF1 and ATIC genes was investigated by methylation-sensitive high-resolution melting (MS-HRM) assay technique and Real-Time PCR. Cancer Genome Atlas (TCGA) dataset was also analyzed for further validation of the gene's methylation.

Results: Methylation of RASSF1 gene promoter was significantly higher in lung tumor tissues. However, promoter methylation levels of ATIC gene was significantly lower in lung tumor tissues. These results were additionally confirmed by TCGA analysis. Promoter methylation of both RASSF1 and ATIC genes was significantly associated with lymph node metastasis, and clinical stage of lung cancer. The receiver operating characteristic (ROC) curve analysis indicated a high accuracy of promoter methylation in these genes as a diagnostic biomarker for lung cancer.

Conclusions: Methylation levels of both RASSF1 and ATIC genes promoters were associated with lung cancer pathogenesis in Iranian population, and may be a suitable biomarker for diagnosis and prognosis of lung cancer in early stage of tumorigenesis.

RASSF1和ATIC基因的启动子甲基化水平与伊朗患者的肺癌相关。
目的:呼吸上皮中肿瘤抑制基因或癌基因的甲基化等表观遗传改变与肺癌有关。基因启动子的高甲基化是一种表观遗传事件,与肿瘤抑制基因失活和癌基因激活有关。本研究旨在评估甲基化状态在RASSF1和ATIC基因启动子中的作用及其在伊朗患者肺肿瘤发病机制中的潜在意义。方法:本研究收集伊朗肺癌患者组织标本100份,其中肺癌组织50份,癌旁非癌组织50份。提取基因组DNA,采用甲基化敏感高分辨率熔融(MS-HRM)分析技术和实时荧光定量PCR检测RASSF1和ATIC基因的甲基化状态。还分析了癌症基因组图谱(TCGA)数据集,以进一步验证该基因的甲基化。结果:RASSF1基因启动子甲基化在肺肿瘤组织中显著升高。然而,ATIC基因启动子甲基化水平在肺肿瘤组织中显著降低。TCGA分析进一步证实了这些结果。RASSF1和ATIC基因启动子甲基化与肺癌的淋巴结转移和临床分期显著相关。受试者工作特征(ROC)曲线分析表明,这些基因的启动子甲基化具有很高的准确性,可作为肺癌的诊断生物标志物。结论:RASSF1和ATIC基因启动子甲基化水平与伊朗人群肺癌发病相关,可能是肿瘤发生早期肺癌诊断和预后的合适生物标志物。
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来源期刊
Hormone Molecular Biology and Clinical Investigation
Hormone Molecular Biology and Clinical Investigation BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
2.60
自引率
0.00%
发文量
55
期刊介绍: Hormone Molecular Biology and Clinical Investigation (HMBCI) is dedicated to the provision of basic data on molecular aspects of hormones in physiology and pathophysiology. The journal covers the treatment of major diseases, such as endocrine cancers (breast, prostate, endometrium, ovary), renal and lymphoid carcinoma, hypertension, cardiovascular systems, osteoporosis, hormone deficiency in menopause and andropause, obesity, diabetes, brain and related diseases, metabolic syndrome, sexual dysfunction, fetal and pregnancy diseases, as well as the treatment of dysfunctions and deficiencies. HMBCI covers new data on the different steps and factors involved in the mechanism of hormone action. It will equally examine the relation of hormones with the immune system and its environment, as well as new developments in hormone measurements. HMBCI is a blind peer reviewed journal and publishes in English: Original articles, Reviews, Mini Reviews, Short Communications, Case Reports, Letters to the Editor and Opinion papers. Ahead-of-print publishing ensures faster processing of fully proof-read, DOI-citable articles.
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