[1]罗世龙a,李志强b,李 翔a.肺癌患者支气管肺泡灌洗液中DAPL1 和MLH1 基因甲基化水平检测及其临床意义研究[J].现代检验医学杂志,2024,39(05):125-129.[doi:10.3969/j.issn.1671-7414.2024.05.023]
　LUO Shilonga,LI Zhiqiangb,LI Xianga.Detection and Clinical Significance of DAPL1 and MLH1 Gene Methylation in Bronchoalveolar Lavage Fluid of Lung Cancer Patients[J].Journal of Modern Laboratory Medicine,2024,39(05):125-129.[doi:10.3969/j.issn.1671-7414.2024.05.023]
点击复制

肺癌患者支气管肺泡灌洗液中DAPL1 和MLH1 基因甲基化水平检测及其临床意义研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年05期
页码:
125-129
栏目:
论著
出版日期:
2024-09-15

文章信息/Info

Title:
Detection and Clinical Significance of DAPL1 and MLH1 Gene Methylation in Bronchoalveolar Lavage Fluid of Lung Cancer Patients
文章编号:
1671-7414（2024）05-125-05
作者:
罗世龙a; 李志强b; 李 翔a
（蒙城县第二人民医院a. 肿瘤内科；b. 营养科，安徽蒙城 233500）
Author(s):
LUO Shilonga;  LI Zhiqiangb;  LI Xianga
（a. Department of Medical Oncology；b. Department of Nutrition，the Second People’s Hospital of Mengcheng County，Anhui Mengcheng 233500，China）
关键词:
肺癌; 支气管肺泡灌洗液; 凋亡相关蛋白激酶样蛋白1; 错配修复基因; 基因甲基化
分类号:
R734.2；R730.43
DOI:
10.3969/j.issn.1671-7414.2024.05.023
文献标志码:
A
摘要:
目的 检测肺癌患者支气管肺泡灌洗液（bronchoalveolar lavage fluid，BALF）中凋亡相关蛋白激酶样蛋白1（death-associated protein kinase like 1，DAPL1）和错配修复基因（Mut L homologue l，MLH1）甲基化水平，进一步研究基因甲基化对早期肺癌的诊断价值及其与临床病理特征的关系。方法 回顾性选取2022 年1 月～ 2024 年1 月蒙城县第二人民医院收治的疑似早期肺癌患者142 例，根据最终病理学结果分为肺癌组（n=82）和肺部良性病变组（n=60）。采用实时定量聚合酶链反应（qRT-PCR）法检测两组BALF 样本中DAPL1 和MLH1 甲基化水平；分析DAPL1 和MLH1 甲基化对早期肺癌的临床诊断价值及其与肺癌患者临床病理特征的关系。结果 肺癌组患者BALF 中DAPL1 和MLH1基因甲基化水平分别为53.66%（44/82），56.10%（46/82），明显高于良性病变组的11.67%（7/60）和18.33%（11/60），差异具有统计学意义（χ2=56.544，20.565，均P ＜ 0.05）。 DAPL1 和MLH1 基因甲基化诊断早期肺癌的敏感度分别为53.66%（44/82）和56.10%（46/82），特异度分别为88.33%（53/60）和81.67%（49/60），准确度分别为68.31%（97/142）和66.90%（95/142）；DAPL1 甲基化联合MLH1 甲基化诊断早期肺癌的敏感度和准确度分别为86.59%（71/82），85.92%（122/142），均高于单一指标（Z=24.411，16.450，均P ＜ 0.05）。肺癌患者BALF 中DAPL1 和MLH1 基因甲基化水平与临床分期、吸烟史及淋巴结转移密切相关（χ2=5.493，13.083；8.167，6.946；9.303，4.523，均P ＜ 0.05）。Spearman 相关性显示，DAPL1 和MLH1 基因甲基化与肺癌患者临床分期、吸烟史及淋巴结转移均呈正相关（r=0.523，0.602；0.548，0.498；0.630，0.524，均P ＜ 0.05）。结论 BALF 中DAPL1 和MLH1 基因甲基化检测对于早期肺癌具有较高的临床诊断价值，且两者基因甲基化水平与肺癌患者病情进展及吸烟史有关。
Abstract:
Objective To detect the expression of death-associated protein kinase like 1 (DAPL1) and mismatch repair gene (Mut L homologue l, MLH1) methylation level in bronchoalveolar lavage fluid (BALF) of patients with lung cancer，and further investigate the diagnostic value of gene methylation in early lung cancer and its relationship with clinicopathological features. Methods A total of 142 patients with suspected early stage lung cancer admitted the Second People’s Hospital of Mengcheng County from January 2022 to January 2024 were retrospectively selected and divided into lung cancer group（n=82）and lung benign lesion group（n=60）according to the final pathological results. Quantitative real time polymerase chain reaction (qRTPCR) was used to detect the methylation levels of DAPL1 and MLH1 in BALF samples. The clinical diagnostic value of DAPL1 and MLH1 methylation in early stage lung cancer and its relationship with clinicopathological features of lung cancer patients were analyzed. Results The methylation levels of DAPL1 and MLH1 gene in BALF in lung cancer group were 53.66% (44/82) and 56.10% (46/82), respectively, which were significantly higher than those in benign disease group [11.67% (7/60) and 18.33% (11/60)] , and the difference was statistically significant (χ2=56.544，20.565，all P < 0.05). The sensitivity of DAPL1 and MLH1 gene methylation in the diagnosis of early lung cancer was 53.66% (44/82) and 56.10% (46/82), the specificity was 88.33% (53/60) and 81.67% (49/60), and the accuracy were 68.31% (97/142) and 66.90% (95/142), respectively. The sensitivity and accuracy of DAPL1 methylation combined with MLH1 methylation in the diagnosis of early lung cancer was 86.59% (71/82), and 85.92% (122/142), respectively, both of which were higher than that of a single index (Z=24.411, 16.450, all P < 0.05). The methylation levels of DAPL1 and MLH1 genes in BALF of lung cancer patients were closely correlated with clinical stage, smoking history and lymph node metastasis (χ2=5.493，13.083；8.167，6.946；9.303，4.523，all P<0.05). Spearman correlation showed that DAPL1 and MLH1 gene methylation were positively correlated with clinical stage, smoking history and lymph node metastasis in patients with lung cancer (r=0.523, 0.602；0.548, 0.498; 0.630, 0.524, all P < 0.05). Conclusion The methylation of DAPL1 and MLH1 genes in BALF has high clinical diagnostic value for early lung cancer, and the methylation levels of both genes are related to the disease progression and smoking history of lung cancer patients.

参考文献/References:

[1] HAR?ARDOTTIR H, JONSSON S, GUNNARSSON O,et al. Advances in lung cancer diagnosis and treatment-a review[J]. Laeknabladid, 2022, 108(1):17-29.
[2] 谢惠杰, 邹红, 吴赓, 等. 血常规炎症指标联合血清肿瘤标志物在肺癌诊断中的价值分析[J]. 检验医学与临床, 2023, 20(6): 758-763. XlE Huijie, ZOU Hong, WU Geng, et al. Analysis on value of blood routine inflammatory indexes combined with serum tumor markers in diagnosis of lung cancer [J]. Laboratory Medicine and Clinic, 2023, 20(6): 758- 763.
[3] NISHIYAMA A, NAKANISHI M. Navigating the DNA methylation landscape of cancer[J]. Trends in Genetics, 2021, 37(11): 1012-1027.
[4] 黄海霞, 乔荣, 李梦夏, 等. 中国人群外周血RABL6基因甲基化与早期肺癌的关联性研究[J]. 安徽医科大学学报, 2023, 58(6): 1030-1036. HUANG Haixia, QIAO Rong, LI Mengxia, et al. The association between RABL6 gene methylation in peripheral blood and early lung cancer in Chinese population [J]. Acta Universitatis Medicinalis Anhui, 2023, 58(6): 1030-1036.
[5] 冯阳阳, 杨燕, 王艳阳, 等. 凋亡相关蛋白激酶样蛋白1 低甲基化对表皮生长因子受体19 外显子缺失突变型肺癌患者预后的影响[J]. 中华肿瘤杂志,2021, 43(12): 1264-1268. FENG Yangyang, YANG Yan, WANG Yanyang, et al. Hypomethylation of DAPL1 associated with prognosis of lung cancer patients with EGFR Del19 mutation [J]. Chinese Journal of Oncology, 2021, 43(12): 1264-1268.
[6] HASHIMOTO R, MATSUSAKA K, MATSUMURA T, et al. The neuroendocrine carcinoma component of gastric mixed adenoneuroendocrine carcinoma could develop with MLH1 deficiency Independent of TP53 mutation[J]. Pathology Internationa, 2023, 73(6): 261-263.
[7] 君安医学细胞平台专家委员会. 支气管肺泡灌洗液细胞形态学检验中国专家共识(2023)[J]. 现代检验医学杂志, 2023, 38(3): 11-16, 23. Expert Committee of J.EDU Medical Cell Platform Soliciting Contributions. Consensus of Chinese Experts on Morphological Examination of bronchoalveolar lavage fluid cells(2023) [J]. Journal of Modern Laboratory Medicine, 2023, 38(3): 11-16, 23.
[8] MCGREGOR L A, DECKARD C E , SMOLEN J A, et al. Thymine DNA glycosylase mediates chromatin phase separation in a DNA methylation-dependent manner[J]. Journal of Biological Chemistry, 2023, 299(7): 104907.
[9] COPPED? F, BHADURI U, STOCCORO A, et al. DNA methylation in the fields of prenatal diagnosis and early detection of cancers[J]. International Journal of Molecular Sciences, 2023, 24(14): 11715.
[10] LIANG Runzhang, LI Xiaosong, LI Weiquan, et al. DNA methylation in lung cancer patients: Opening a “window of life” under precision medicine[J]. Biomedicine and Pharmacotherapy, 2021, 144:112202.
[11] 李君兰, 雷蕾, 金琳羚, 等. 纤维支气管镜吸痰联合肺泡灌洗在肺癌术后合并肺部感染患者中的临床应用价值[J]. 现代生物医学进展, 2022, 22(2):264-267,263. LI Junlan, LEI lei, JIN Linling, et al. Clinical value of fiberoptic bronchoscope sputum suction combined with dveolar lavage in patients with lung infection after lung cancer surgery [J]. Progress in Modern Biomedicine, 2022, 22(2):264-267, 263.
[12] ZHANG Lan, LUO Boqin, LU Yingying, et al. Targeting death-associated protein kinases for treatment of human diseases: recent advances and future directions[J]. Journal of Medicinal Chemistry, 2023, 66(2):1112-1136.
[13] 李永强. 结、直肠癌中错配修复蛋白MLH1, PMS2,SH2, MSH6 的表达及与其临床病理特征的关系分析[J]. 实用癌症杂志, 2023, 38(12): 1997-2000, 2008. LI Yongqiang. Analysis of correlation between the expression of mismatch repair proteins(MLH1, MSH2, PMS2 and MSH6) and clinicopathological characteristics in colorectal carcinoma [J].The Practical Journal of Cancer, 2023, 38(12): 1997-2000, 2008.
[14] MA Xiaoyin, LI Huirong, WANG Yipin, et al. DAPL1, a susceptibility locus for age-related macular degeneration, acts as a novel suppressor of cell proliferation in the retinal pigment epithelium[J]. Human Molecular Genetics, 2017, 26(9): 1612-1621.
[15] 冷雪, 马建群. m6A 甲基化在肺癌中的研究进展[J].现代肿瘤医学, 2024, 32(6): 1167-1172. LENG Xue, MA Jianqun. Research progress of m6A methylation in lung cancer [J]. Journal of Modern Oncology, 2024, 32(6): 1167-1172.
[16] 王延宁, 孙宇, 刘俊, 等. 非小细胞肺癌中MGMT 基因表达和MLH1 基因异常甲基化与临床特征的相关性研究[J]. 广西医科大学学报, 2018, 35(3): 344-347. WANG Yanning, SUN Yu, LIU Jun, et al. The correlation between MGMT expression and MLH1 abnormal methylation and clinical features in nonsmall cell lung cancer patients [J]. Journal of Guangxi Medical University, 2018, 35(3): 344-347.

相似文献/References:

[1]马丽颜,梁 静,周建龙.腺瘤样结肠息肉易感基因(APC)及结直肠癌缺失基因(DCC)基因甲基化在肺癌早期诊断的意义[J].现代检验医学杂志,2016,31(01):17.[doi:10.3969/j.issn.1671-7414.2016.01.005]
　MA Li-yan,LIANG Jing,ZHOU Jian-long.Evaluation of the Combination of APC and DCC Gene Methylation in the Early Diagnosis of Lung Cancer[J].Journal of Modern Laboratory Medicine,2016,31(05):17.[doi:10.3969/j.issn.1671-7414.2016.01.005]
[2]彭 瑛,邓正华,温先勇.国内13种血清肿瘤标志物对肺癌诊断价值的Meta分析[J].现代检验医学杂志,2016,31(01):96.[doi:10.3969/j.issn.1671-7414.2016.01.028]
　PENG Ying,DENG Zheng-hua,WEN Xian-yong.Diagnostic Value of Thirteen Types of Serum Tumor Markers for Lung Cancer in China:A Meta-Analysis[J].Journal of Modern Laboratory Medicine,2016,31(05):96.[doi:10.3969/j.issn.1671-7414.2016.01.028]
[3]翟海军,朱晶.红细胞分布宽度对肺癌预后的临床分析[J].现代检验医学杂志,2015,30(06):147.[doi:10.3969/j.issn.1671-7414.2015.06.045]
　ZHAI Hai-jun,ZHU Jing.Clinical Analysis of Red Blood Cell Distribution Width on the Prognosis of Lung Cancer[J].Journal of Modern Laboratory Medicine,2015,30(05):147.[doi:10.3969/j.issn.1671-7414.2015.06.045]
[4]姜 波,王玉明,段 勇.肺癌组织中调控PUMA基因 的miRNA筛查和MiR-221表达差异研究[J].现代检验医学杂志,2015,30(01):15.[doi:10.3969/j.issn.1671-7414.2015.01.005]
　JIANG Bo,WANG Yu-ming,DUAN Yong.Study on the Differential Expression of miRNA Screening and MiR-221 Regulates Apoptosis by Targeting PUMA Gene in Lung Cancer[J].Journal of Modern Laboratory Medicine,2015,30(05):15.[doi:10.3969/j.issn.1671-7414.2015.01.005]
[5]赵车冬,闫玉珠,吴文婧,等.血清CEA,CYFRA21-1,NSE水平在肺癌诊断与分型中的应用价值[J].现代检验医学杂志,2016,31(06):59.[doi:10.3969/j.issn.1671-7414.2016.06.016]
　ZHAO Che-dong,YAN Yu-zhu,WU Wen-jing,et al.Application Value of Serum CEA,CYFRA21-1 and NSE Levels in the Diagnosis and Typing of Lung Cancer[J].Journal of Modern Laboratory Medicine,2016,31(05):59.[doi:10.3969/j.issn.1671-7414.2016.06.016]
[6]董 莉,张保平,冯新平,等.血浆HSP90α检测在肺癌诊断中的临床应用价值研究[J].现代检验医学杂志,2017,32(04):97.[doi:10.3969/j.issn.1671-7414.2017.04.027]
　DONG Li,ZHANG Bao-ping,FENG Xin-ping,et al.Plasma HSP90 Alpha Testing Clinical Application Value in the Diagnosis of Lung Cancer Researc[J].Journal of Modern Laboratory Medicine,2017,32(05):97.[doi:10.3969/j.issn.1671-7414.2017.04.027]
[7]张利祥,潘 静,赵 洁,等.痰液基细胞学检查与血清CYFRA21-1,CEA,NSE联合检测对肺癌的诊断价值[J].现代检验医学杂志,2019,34(03):99.[doi:10.3969/j.issn.1671-7414.2019.03.024]
　ZHANG Li-xiang,PAN Jing,ZHAO Jie,et al.Value of the Combined Determination of Sputum Liquid-Based Cytologyand Serum CYFRA21-1,CEA,NSE for the Diagnosis of Lung Cancer[J].Journal of Modern Laboratory Medicine,2019,34(05):99.[doi:10.3969/j.issn.1671-7414.2019.03.024]
[8]樊　华,弥　鹏,杨　波,等.肺癌患者外周血血小板参数检测分析及临床意义[J].现代检验医学杂志,2019,34(06):97.[doi:10.3969 ／ j.issn.1671-7414.2019.06.024]
　FAN Hua,MI Peng,YANG Bo,et al.Analysis and Clinical Value of Peripheral Platelet Parameters in Lung Cancer Patients[J].Journal of Modern Laboratory Medicine,2019,34(05):97.[doi:10.3969 ／ j.issn.1671-7414.2019.06.024]
[9]赵格a,高琼b,余宗涛a,等.肺癌患者血浆miR-3151 表达水平与临床病理特征的相关性研究[J].现代检验医学杂志,2020,35(05):28.[doi:10.3969/j.issn.1671-7414.2020.05.008]
　ZHAO Gea,GAO Qiongb,YU Zong-taoa,et al.Study on the Correlation between the Expression of miR-3151 in Plasma and Clinicopathological Features in Patients with Lung Cancer[J].Journal of Modern Laboratory Medicine,2020,35(05):28.[doi:10.3969/j.issn.1671-7414.2020.05.008]
[10]周道银,吴 茅,许绍强,等.支气管肺泡灌洗液细胞形态学检验中国专家共识[J].现代检验医学杂志,2020,35(06):4.[doi:doi:10.3969/j.issn.1671-7414.2020.06.002]
　ZHOU Dao-yin,WU Mao,XU Shao-qiang,et al.Consensus of Chinese Experts on Morphological Examination of Bronchoalveolar Lavage Fluid Cells（2020）[J].Journal of Modern Laboratory Medicine,2020,35(05):4.[doi:doi:10.3969/j.issn.1671-7414.2020.06.002]

备注/Memo

备注/Memo:
作者简介： 罗世龙（1985-），男，本科，主治医师，研究方向：肿瘤的穿刺、化疗、靶向、免疫以及介入治疗，E-mail: 15256737286@163.com。
更新日期/Last Update: 2024-09-15