肺腺癌胸腔积液DNA倍体异常与EGFR突变的关系及其对患者预后的影响

doi:10.3969/j.issn.1004-616x.2023.03.003

摘要/Abstract

摘要： 目的：回顾性分析转移性肺腺癌胸腔积液细胞的DNA倍体异常和表皮生长因子受体(EGFR)基因突变的关系，及其对肺腺癌患者预后的影响。方法：收集河北医科大学第四医院2012—2019年439例肺腺癌伴恶性胸腔积液患者的临床资料。使用计算机辅助DNA倍体定量分析系统检测胸腔积液中肺腺癌细胞DNA含量，计算大于5c细胞的百分比、大于9c细胞的数目、最大DNA指数(DI)值、大于5c细胞的平均DI值及非整倍体细胞峰。比较DNA倍体异常、EGFR基因突变各组间的差异，并检验DNA倍体异常与EGFR突变的相关性，分析DNA倍体异常及EGFR基因突变在肺腺癌预后中的价值。结果：439例肺腺癌患者中，共有244例(55.58%)检测出EGFR基因突变。与对照组比较，男性、有吸烟史、大于5c细胞的百分比<14%、大于9c细胞的数目<8、最大DI值<6、大于5c细胞的平均DI值<5的患者，其EGFR基因突变率降低(P<0.05)。不同非整倍体细胞峰的EGFR基因突变率不同，双峰和单峰比无峰的EGFR突变率高(P<0.05)，而多峰与其他组的EGFR突变率差异无统计学意义(P>0.05)。与EGFR野生型患者相比，EGFR突变型患者的大于5c细胞的百分比、大于9c细胞的数目、最大DI值、大于5c细胞的平均DI值及非整倍体细胞峰的平均秩次更高(P<0.05)，且上述5项指标均与EGFR突变均存在较弱的正相关关系(Kendall's tau-b相关系数分别为0.186、0.153、0.110、0.156、0.148，均为P<0.05)。单因素生存分析显示，大于5c细胞的百分比≥14%、大于9c细胞的数目≥8、EGFR突变患者的中位总生存时间较对照组患者长(P<0.05)。多因素生存分析显示，EGFR基因突变是晚期肺腺癌患者的独立预后影响因素。结论：晚期肺腺癌患者中EGFR基因突变与DNA倍体异常存在关联，DNA倍体异常可能是预测EGFR基因突变的潜在指标。DNA倍体异常不是晚期肺腺癌患者的独立预后因素，但EGFR基因突变患者预后优于野生型患者。

关键词: DNA倍体异常, EGFR基因突变, 肺腺癌, 计算机辅助, 预后

Abstract: OBJECTIVE：Relationships between DNA ploidy abnormality and epidermal growth factor receptor (EGFR) gene mutation in pleural effusion from metastatic lung adenocarcinomas and their effects on prognosis of patients. METHODS：Clinical data of 439 patients with lung adenocarcinomas and with malignant pleural effusions were collected from the Fourth Hospital of Hebei Medical University from 2012 to 2019. DNA content in cells from pleural effusions was detected by computer aided DNA ploidy quantitative analysis. Percentages of cells with greater than 5c，the number of cells with greater than 9c，the maximum DNA index (DI) value，the average DI value of cells with greater than 5c and the peak of aneuploid cells were calculated. Differences of DNA ploidy and EGFR gene mutation among groups were compared，and correlations between DNA ploidy and EGFR mutation were tested to analyze the values of DNA ploidy and EGFR gene mutation in prognosis of lung adenocarcinoma. RESULTS：EGFR mutations were detected in 244 (55.58%) of 439 patients. The mutation rate was significantly reduced in male patients，and in patients with a history of smoking，compared to the controls (P<0.05). In addition，the percentage of cells greater than 5c <14%，the number of cells greater than 9c <8，the maximum DI value <6，and the mean value of cells greater than 5c <5 (P<0.05). The mutation rate of EGFR gene was different with different aneuploid cell peak，and compared with the nonpeak group，the mutation rate of EGFR gene was higher with single and double peak (P<0.05)，while there was no significant difference in EGFR mutation rate between multi-peak and other groups. Compared with the EGFR wild-type patients，EGFR mutant patients had a higher mean rank in the percentage of cells greater than 5c，the number of cells greater than 9c，the maximum DI，the mean DI of cells greater than 5c，and the aneuploid cell peak number，and all five indexes were weakly positively correlated with EGFR mutation. Univariate survival analysis showed that the median overall survival time of patients with greater than 5c cell percentage ≥14%，greater than 9C cell number ≥8 and EGFR mutation were longer than that of the controls. Multivariate survival analysis showed that DNA ploidy was not associated with patient prognosis，and EGFR gene mutation was an independent prognostic factor in patients with advanced lung adenocarcinoma. CONCLUSION：There was a positive correlation between EGFR gene mutation and DNA ploidy abnormality in patients with advanced lung adenocarcinoma，and DNA ploidy abnormality was a potential predictor of EGFR gene mutation. DNA ploidy was not an independent prognostic factor in patients with advanced lung adenocarcinoma. Patients with EGFR gene mutation had a better prognosis than the wild-type patients.

Key words: DNA ploidy abnormality, EGFR mutation, lung adenocarcinoma, computer aided, prognosis

中图分类号:

R734.2

刘颖, 王蕊, 郭晓, 董律吏, 张艳, 赵银环, 杜芸. 肺腺癌胸腔积液DNA倍体异常与EGFR突变的关系及其对患者预后的影响[J]. 癌变·畸变·突变, 2023, 35(3): 178-182,186.

LIU Ying, WANG Rui, GUO Xiao, DONG Lüli, ZHANG Yan, ZHAO Yinhuan, DU Yun. Relationships between DNA ploidy abnormality and EGFR mutation in pleural effusions, and their effects on prognosis of lung adenocarcinomas[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(3): 178-182,186.

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