Pastuszak-Lewandoska D, Czarnecka K H, Migdalska-Sęk M, Nawrot E, Domańska D, Kiszałkiewicz J, Kordiak J, Antczak A, Górski P, Brzeziańska-Lasota E
Department of Molecular Bases of Medicine, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland.
Adv Exp Med Biol. 2015;852:39-48. doi: 10.1007/5584_2014_109.
Lung cancer is the leading cause of cancer-related death in the world. Early detection, based on molecular markers, could decrease mortality from this disease. Tumor development is often associated with inactivation or loss of tumor suppressor genes (TSGs). The aim of the present study was to analyze the expression level of FAM107A gene, a TSG located in 3p21.1, in lung cancer tumors and in tumor adjacent normal lung samples. Promoter methylation status of FAM107A was evaluated as the potential mechanism of its epigenetic silencing. The relationship between gene mRNA expression and tumor staging, metastasis status, and non-small cell lung cancer (NSCLC) histopathological subtypes in 60 patients was analyzed. Total RNA was isolated from tissue samples and gene expression was assessed in qPCR assay. Gene promoter methylation status was evaluated in MSP reactions, using bisulfite converted DNA and two pairs of primers: methylated and unmethylated. We found that the expression of the gene was dramatically decreased in all NSCLC samples and was significantly lower than in tumor adjacent normal lung tissue. Promoter methylation of FAM107A gene was confirmed only in the minority of NSCLCs. The results highlight the importance of FAM107A in lung carcinogenesis, although indicate other than promoter hypermethylation mechanism of the gene decreased expression.
肺癌是全球癌症相关死亡的主要原因。基于分子标志物的早期检测可降低该疾病的死亡率。肿瘤发展通常与肿瘤抑制基因（TSG）的失活或缺失有关。本研究的目的是分析位于3p21.1的TSG基因FAM107A在肺癌肿瘤组织及肿瘤旁正常肺组织样本中的表达水平。评估FAM107A的启动子甲基化状态作为其表观遗传沉默的潜在机制。分析了60例患者中基因mRNA表达与肿瘤分期、转移状态及非小细胞肺癌（NSCLC）组织病理学亚型之间的关系。从组织样本中提取总RNA，并通过qPCR检测评估基因表达。使用亚硫酸氢盐转化的DNA和两对引物（甲基化和未甲基化引物）在MSP反应中评估基因启动子甲基化状态。我们发现，该基因在所有NSCLC样本中的表达均显著降低，且明显低于肿瘤旁正常肺组织。仅在少数NSCLC中证实了FAM107A基因的启动子甲基化。结果突出了FAM107A在肺癌发生中的重要性，尽管表明该基因表达降低的机制并非启动子高甲基化。
