[1]周红梅a,赵晓彬a,吴亚光a,等.外周血DLGAP5和RASSF1A基因甲基化对肺结节良恶性诊断价值研究[J].现代检验医学杂志,2025,40(02):53-58.[doi:10.3969/j.issn.1671-7414.2025.02.010]
　ZHOU Hongmeia,ZHAO Xiaobina,WU Yaguanga,et al.Value of Peripheral Blood DLGAP5 and RASSF1A Gene Methylation in the Differential Diagnosis of Benign and Malignant Lung Nodules[J].Journal of Modern Laboratory Medicine,2025,40(02):53-58.[doi:10.3969/j.issn.1671-7414.2025.02.010]
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外周血DLGAP5和RASSF1A基因甲基化对肺结节良恶性诊断价值研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年02期
页码:
53-58
栏目:
论著
出版日期:
2025-03-15

文章信息/Info

Title:
Value of Peripheral Blood DLGAP5 and RASSF1A Gene Methylation in the Differential Diagnosis of Benign and Malignant Lung Nodules
文章编号:
1671-7414（2025）02-053-06
作者:
周红梅a; 赵晓彬a; 吴亚光a; 肖 敬b
（河北省第七人民医院a. 肺病科；b. 肿瘤科，河北定州073000）
Author(s):
ZHOU Hongmeia;  ZHAO Xiaobina;  WU Yaguanga;  XIAO Jingb
（a. Department of Pulmonology; b. Department of Oncology , Hebei Seventh People’s Hospital, Hebei Dingzhou 073000, China）
关键词:
肺结节; 良恶性鉴别; Discs 大同源物相关蛋白5; Ras 相关区域家族蛋白1A
分类号:
R734.2；R730.43
DOI:
10.3969/j.issn.1671-7414.2025.02.010
文献标志码:
A
摘要:
目的 探究外周血Discs 大同源物相关蛋白5（DLGAP5）和Ras 相关区域家族蛋白1A（RASSF1A）甲基化水平对肺结节良恶性鉴别诊断的价值。方法 选取2022 年12 月～ 2024 年6 月河北省第七人民医院收治的110 例肺结节患者作为研究对象。根据病理检查确诊，将52 例恶性肺结节患者纳入恶性组，58 例良性肺结节患者纳入良性组。通过实时定量聚合酶链反应（qRT-PCR）法测定外周血DLGAP5 和RASSF1A 基因甲基化水平；分析外周血DLGAP5和RASSF1A 基因甲基化对肺结节良恶性的诊断价值及其与恶性肺结节患者临床病理特征的关系；采用Spearman 法分析DLGAP5 和RASSF1A 基因甲基化水平与临床病理特征的相关性。结果 与良性组相比，恶性组患者外周血DLGAP5和RASSF1A 基因甲基化水平均较高，差异具有统计学意义（χ2=27.010，24.350, 均P<0.001）；DLGAP5 甲基化和RASSF1A 甲基化单独检测恶性肺结节的敏感度分别为61.54%，67.31%，特异度分别为86.21%，79.31%，准确度分别为74.55%，73.63%。且两基因甲基化联合检测对恶性肺结节的敏感度（84.62%）和准确度（83.64%）均优于单个基因甲基化（Z=2.816，2.497, 均P<0.05）。DLGAP5 甲基化和RASSF1A 甲基化单独检测及联合检测与病理结果的一致性Kappa 值分别为0.583，0.569 和0.712。恶性肺结节患者结节大小、组织学分化程度、淋巴结转移及毛刺征与DLGAP5 和RASSF1A 甲基化水平相关，差异具有统计学意义（χ2DLGAP5=4.644 ～ 14.981，χ2RASSF1A=4.293 ～ 12.629，均P<0.05）。相关性分析显示，DLGAP5 和RASSF1A 基因甲基化水平与结节大小、组织学分化、淋巴结转移和毛刺征呈正相关(rDLGAP5=0.512~0.683，rRASSF1A=0.527 ～ 0.691，均P<0.05)。结论 外周血中DLGAP5 和RASSF1A 基因甲基化与组织学分化、淋巴结转移、临床分期密切相关，二者联合检测对肺结节良恶性具有较高的鉴别诊断价值。
Abstract:
Objective To investigate the value of methylation levels of Discs large-associated protein5 (DLGAP5) and Ras association domain family 1A (RASSF1A) in peripheral blood in the differential diagnosis of benign and malignant lung nodules. Methods 110 patients with pulmonary nodules admitted to the Seventh People’s Hospital of Hebei Province from December 2022 to June 2024 were selected as study subjects. Based on the diagnosis confirmed by pathological examination, 52 patients with malignant lung nodules were included in the malignant group and 58 patients with benign lung nodules were included in the benign group. The methylation levels of DLGAP5 and RASSF1A genes in peripheral blood were determined by quantitative realtime polymerase chain reaction (qRT-PCR). The diagnostic value of methylation of DLGAP5 and RASSF1A genes in peripheral blood on the benign and malignant nature of lung nodules and their relationship with clinicopathological characteristics of patients with malignant lung nodules were analyzed. Spearman’s method was used to analyze the correlation between DLGAP5 and RASSF1A gene methylation levels and clinicopathological features. Results Compared with the benign group, the methylation levels of DLGAP5 and RASSF1A genes were higher in the peripheral blood of patients in the malignant group, and the differences were statistically significant (χ2=27.010, 24.350, all P<0.001). The sensitivities of DLGAP5 methylation and RASSF1A methylation alone in the detection of malignant lung nodules were 61.54%, 67.31%, and the specificity were 86.21%, 79.31%, and the accuracies were 74.55%, 73.63%, respectively. The sensitivity(84.62%) and accuracy(83.64%) of the combined two-gene methylation test for malignant lung nodules were better than that of single gene methylation (Z=2.816, 2.497, all P<0.05). The concordance Kappa values of DLGAP5 methylation and RASSF1A methylation alone and in combination with the pathological results were 0.583, 0.569 and 0.712, respectively . The nodules size, histological differentiation degree, lymph nodes and spiculation sign of patients with malignant pulmonary nodules were correlated with DLGAP5 and RASSF1A methylation levels, and the differences were statistically significant (χ2 DLGAP5=4.644 ～ 14.981, χ2 RASSF1A=4.293 ～ 12.629, all P<0.05). Correlation analysis showed that the methylation levels of DLGAP5 and RASSF1A genes were positively correlated with nodule size, histologic differentiation, lymph node metastasis and spiculation sign (rDLGAP5=0.512~0.683, rRASSF1A=0.527 ～ 0.691, all P<0.05). Conclusion The methylation levels of DLGAP5 and RASSF1A gene in peripheral blood were closely related to histological differentiation , lymph node metastasis and clinical staging. The combined detection of the two has high diagnostic value fro the benign and malignant nature of pulmonary nodules.

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备注/Memo

备注/Memo:
作者简介：周红梅（1981-），女，本科，副主任医师，研究方向：肺病相关研究，E-mail：trabiton@sina.com。
通讯作者：肖敬（1981-），女，本科，副主任医师，研究方向：肿瘤相关研究，E-mail：117307081@qq.com。
更新日期/Last Update: 2025-03-15