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血浆游离DNA甲基化联合肿瘤突变检测在非小细胞肺癌(NSCLC)患者预后预测中的应用

Plasma cell-free DNA methylation combined with tumor mutation detection in prognostic prediction of patients with non-small cell lung cancer (NSCLC).

作者信息

Guo Dan, Yang Liang, Yang Jianwei, Shi Ke

机构信息

Department of Medicine.

Department of Microbiology and Immunology and Medicine, Henan Medical College.

出版信息

Medicine (Baltimore). 2020 Jun 26;99(26):e20431. doi: 10.1097/MD.0000000000020431.

Abstract

BACKGROUND

Lung Cancer is one of the most common cancers with high degree of malignancy, is a devastating disease with a poor prognosis worldwide. prognostic prediction for patients with non small-cell lung cancer (NSCLC) is still challenge.

MATERIAL AND METHODS

The cohort consisted of 64 consecutive patients with NSCLC identified from June1, 2014, to June 30, 2018. Liquid biopsy samples were collected. Genomic mutation DNA was calculated by including all substitutions and indels over the entire somatic, coding, sequencing length. statistical evaluations were carried out using SPSS software.

RESULTS

Quantity of total ctDNA was successfully determined in all 64 patients from whom baseline circulating DNA was available. ctDNA concentration ranged from 4000 to 3,562,000 genome equivalents per milliliter. Treatments induced a significant decrease in cancer specific markers in most patients with response to treatments, while the methylated DNA demonstrated favorable prediction efficiency regardless of the response status. Patients with ctDNA mutation and methylated DNA decreasing have favorable overall survival (P < .05). combination of genetic and methylated DNA decreasing had high reliability in predicting overall survival of patients with NSCLC.

CONCLUSIONS

We have detected both tumor mutations and methylated DNA in plasma of patients with NSCLC. Combined genetic and methylated DNA decreasing after treatment was an independent risk factor for prognosis of patients with NSCLC. Meanwhile, it had favorable predict value and had potential to be defined as a novel biomarker for patients with NSCLC.

摘要

背景

肺癌是最常见的恶性肿瘤之一,是一种在全球范围内预后不良的毁灭性疾病。非小细胞肺癌(NSCLC)患者的预后预测仍然具有挑战性。

材料与方法

该队列包括2014年6月1日至2018年6月30日期间连续纳入的64例NSCLC患者。收集液体活检样本。通过纳入整个体细胞、编码、测序长度上的所有替换和插入缺失来计算基因组突变DNA。使用SPSS软件进行统计评估。

结果

在所有64例可获得基线循环DNA的患者中成功测定了总ctDNA量。ctDNA浓度范围为每毫升4000至3562000基因组当量。治疗使大多数对治疗有反应的患者的癌症特异性标志物显著降低,而甲基化DNA无论反应状态如何均显示出良好的预测效率。ctDNA突变且甲基化DNA降低的患者总生存期良好(P<0.05)。基因和甲基化DNA降低的联合在预测NSCLC患者总生存期方面具有高可靠性。

结论

我们在NSCLC患者血浆中检测到肿瘤突变和甲基化DNA。治疗后基因和甲基化DNA联合降低是NSCLC患者预后的独立危险因素。同时,它具有良好的预测价值,有潜力被定义为NSCLC患者的新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1c9/7328949/aff928c75785/medi-99-e20431-g002.jpg

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