非小细胞肺癌矮小同源盒基因2和Ras相关结构域蛋白家族1A基因甲基化的意义

doi:10.3969/j.issn.1006-6233.2023.10.005

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摘要 目的:探究矮小同源盒基因(SHOX2)和Ras相关结构域蛋白家族1A(RASSF1A)基因甲基化与非小细胞肺癌(NSCLC)浸润、转移的关系。方法:采用甲基化特异性PCR法(MSP)分析NSCLC及其相应癌旁组织中SHOX2和RASSF1A基因启动子区甲基化状态,分析其甲基化状态与患者临床病理特征的关系。结果:NSCLC癌组织中SHOX2和RASSF1A基因启动子区甲基化率分别为68.97%(80/116)、33.62%(39/116),明显高于癌旁正常组织中的12.93%(15/116)、10.34%(12/116)(P<0.05);SHOX2和RASSF1A基因甲基化分布情况与NSCLC患者性别、年龄、吸烟史、肿瘤直径、分化程度无关(P>0.05),与其TNM分期、病理分型、淋巴结转移以及患者生存时间有关(P<0.05),TNM分期中Ⅲa+Ⅲb期患者SHOX2基因甲基化率明显高于Ⅰ+Ⅱ期患者(P<0.05),鳞癌患者基因甲基化率明显高于腺癌患者(P<0.05),有淋巴结转移患者基因甲基化率明显高于无淋巴结转移患者(P<0.05),生存时间<2年患者基因甲基化率明显高于生存时间≥2年患者(P<0.05);TNM分期中Ⅲa+Ⅲb期患者RASSF1A基因甲基化率明显高于Ⅰ+Ⅱ期患者(P<0.05),腺癌患者基因甲基化率明显高于鳞癌患者(P<0.05),有淋巴结转移患者基因甲基化率明显高于无淋巴结转移患者(P<0.05),生存时间<2年患者基因甲基化率明显高于生存时间≥2年患者(P<0.05)。结论:SHOX2和RASSF1A基因启动子区甲基化可能是NSCLC发生浸润以及转移的原因之一,检测SHOX2和RASSF1A基因启动子区甲基化可为NSCLC的诊断及预后评估提供参考价值。

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	张旭光
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关键词 ：矮小同源盒基因, Ras相关结构域蛋白家族1A, 非小细胞肺癌, 甲基化

Abstract：Objective: To explore the relationship between the gene methylation of dwarf stature homeobox-containing gene (SHOX2) and Ras-related domain protein family 1A (RASSF1A) and the invasion and metastasis of non-small cell lung cancer (NSCLC). Methods: Methylation-specific PCR (MSP) was used to analyze the methylation status of SHOX2 and RASSF1A gene promoter regions in NSCLC and its corresponding adjacent tissues, and the relationship between methylation status and clinical pathological features of patients was analyzed. Results: The methylation rates of SHOX2 and RASSF1A gene promoter regions in NSCLC cancer tissues were 68.97% (80/116) and 33.62% (39/116) respectively, which were significantly higher than those in normal adjacent tissues with 12.93% (15/116) and 10.34% (12/116) (P<0.05). SHOX2 and RASSF1A gene methylation distribution had no relationship with gender, age, smoking history, tumor diameter, and differentiation degree of NSCLC patients (P>0.05), but had something to do with TNM stage, pathological classification, lymph node metastasis, and survival time (P<0.05). The methylation rate of SHOX2 gene in patients with TNM stage IIIa +IIIb was significantly higher than that in patients with stage I + II (P<0.05), and the gene methylation rate of patients with squamous carcinoma was significantly higher than that of patients with adenocarcinoma (P<0.05), and the gene methylation rate in patients with lymph node metastasis was significantly higher than that in patients without lymph node metastasis (P<0.05), and the gene methylation rate in patients with survival time <2 years was significantly higher than that in patients with survival time ≥ 2 years (P<0.05). The RASSF1A gene methylation rate in patients with TNM stage IIIa + IIIb was significantly higher than that in patients with stage I + II (P<0.05), and the gene methylation rate of patients with adenocarcinoma was significantly higher than that in patients with squamous carcinoma (P<0.05), and the gene methylation rate in patients with lymph node metastasis was significantly higher than that in patients without lymph node metastasis (P<0.05), and the gene methylation rate in patients with survival time< 2 years was significantly higher than that in patients with survival time≥ 2 years (P<0.05). Conclusion: The methylation of SHOX2 and RASSF1A gene promoter regions in NSCLC tissues may be one of the reasons for the invasion and metastasis of NSCLC. Detection of SHOX2 and RASSF1A gene promoter methylation can provide reference value for diagnosis of NSCLC and evaluation of prognosis.

Key words： Dwarf stature homeobox-containing gene Ras-related domain protein family 1A Non-small cell lung cancer Methylation

基金资助:山西省自然科学基金计划项目,(编号:2020011417)

引用本文:

张旭光, 达海丽, 邢文婷. 非小细胞肺癌矮小同源盒基因2和Ras相关结构域蛋白家族1A基因甲基化的意义[J]. 河北医学, 2023, 29(10): 1612-1617.
ZHANG Xuguang, DA Haili, XING Wenting. Significance of Methylation of Dwarf Homology Box Gene 2 and Ras-Related Structural Domain Protein Family 1A Genes in Non-Small Cell Lung Cancer. HeBei Med, 2023, 29(10): 1612-1617.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.10.005 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I10/1612

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