Predictive efficacy of minimal residual disease detection based on ctDNA on survival of non-small cell lung cancer after radical surgery

CHEN Zheng-yu; ZHOU Wei; XIONG Jing; LI Qiang; ZHAO Qiao-dan; LIANG Dong; AI Cheng

doi:10.11659/jjssx.10E022124

您当前的位置：

首页 >

文章列表页 >

Predictive efficacy of minimal residual disease detection based on ctDNA on survival of non-small cell lung cancer after radical surgery

Clinical Research | 更新时间：2023-05-26

- Predictive efficacy of minimal residual disease detection based on ctDNA on survival of non-small cell lung cancer after radical surgery
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 32, Issue 5, Pages: 416-420(2023)
- 作者机构：
  
  1.重庆医科大学第一临床学院/重庆医科大学附属第一医院全科医学科/胸外科，重庆 400016
  2.重庆医科大学基础医学院，重庆 400016
  3.重庆医科大学附属璧山医院胸心外科，重庆402760
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.10E022124
  CLC： R734.2
- Published：25 May 2023，
  
  Received：24 October 2022，
扫描看全文
晨正宇,周薇,熊婧等.基于ctDNA的分子残留病灶检测对非小细胞肺癌根治术后生存的预测效能[J].局解手术学杂志,2023,32(05):416-420.

CHEN Zheng-yu,ZHOU Wei,XIONG Jing,et al.Predictive efficacy of minimal residual disease detection based on ctDNA on survival of non-small cell lung cancer after radical surgery[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(05):416-420.
晨正宇,周薇,熊婧等.基于ctDNA的分子残留病灶检测对非小细胞肺癌根治术后生存的预测效能[J].局解手术学杂志,2023,32(05):416-420. DOI： 10.11659/jjssx.10E022124.

CHEN Zheng-yu,ZHOU Wei,XIONG Jing,et al.Predictive efficacy of minimal residual disease detection based on ctDNA on survival of non-small cell lung cancer after radical surgery[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(05):416-420. DOI： 10.11659/jjssx.10E022124.

摘要

目的

探讨基于循环肿瘤DNA（ctDNA）的分子残留病灶（MRD）检测对非小细胞肺癌（NSCLC）患者根治术后近远期生存的预测效能。

方法

选取重庆医科大学附属第一医院胸外科行根治术治疗的114例NSCLC患者为研究对象，于术后1周采集患者静脉血，采用液态活检和二代测序技术检测ctDNA MRD。统计患者术后MRD阳性率，并分析其与临床病理特征的关系。记录患者术后1年、5年生存情况，采用

Kaplan

Meier

生存曲线比较MRD阳性和阴性患者的近远期生存率，采用

Cox

回归模型分析NSCLC根治术后近远期生存的影响因素，分析MRD检测对NSCLC根治术后近远期生存的预测效能。

结果

NSCLC患者术后MRD阳性率为36.84%，低/未分化、肿瘤直径

3 cm、纵隔淋巴结转移、TNM分期ⅢA期的NSCLC患者MRD阳性率分别高于高/中分化、肿瘤直径≤3 cm、无纵隔淋巴结转移、TNM分期Ⅰ~Ⅱ期患者（

0.05）。NSCLC患者术后1年、5年生存率分别为83.33%、52.63%，MRD阳性患者近远期生存率均低于MRD阴性患者（

0.001）。低/未分化、肿瘤直径

3 cm、TNM分期ⅢA期、术后MRD阳性均是影响NSCLC根治术后患者近远期生存的危险因素（

0.05），而纵隔淋巴结转移是影响NSCLC根治术后患者远期生存的危险因素（

0.05）。术后MRD预测NSCLC患者根治术后近期生存的灵敏度、特异度、准确度分别为73.68%、89.47%、76.32%，预测远期生存的灵敏度、特异度、准确度分别为95.00%、72.22%、84.21%。

结论

NSCLC患者MRD阳性率与肿瘤分化程度、TNM分期、肿瘤大小等有关，是影响NSCLC根治术后近远期生存的危险因素，且对近远期生存预测具有重要价值。

Abstract

Objective

To investigate the predictive efficacy of minimal residual disease (MRD) detection based on circulating tumor DNA (ctDNA) on the short-term and long-term survivals of patients with non-small cell lung cancer (NSCLC) after radical surgery.

Methods

A total of 114 patients with NSCLC who underwent radical surgery in the Department of Thoracic Surgery of First Affiliated Hospital of Chongqing Medical University were included

and the venous blood samples of patients 1 week after surgery were collected

and ctDNA MRD was detected by liquid biopsy and second-generation sequencing technology.The positive rate of MRD after surgery was counted

and its relationship with clinicopathological features was analyzed.The 1-year and 5-year survivals of patients after surgery was recorded.The short-term and long-term survival rates of MRD positive patients and negative patients were compared by

Kaplan

Meier

survival curve.The influencing factors of short-term and long-term survivals after NSCLC radical surgery were analyzed by

Cox

regression model

and the predictive efficacy of MRD detection on short-term and long-term survivals after NSCLC radical surgery was analyzed.

Results

The positive rate of MRD in NSCLC patients after surgery was 36.84%.The positive rate of MRD in NSCLC patients with low/undifferentiated tumor

tumor diameter

3 cm

mediastinal lymph node metastasis and TNM stage of ⅢA was higher than that in patients with high/moderate differentiation tumor

tumor diameter≤3 cm

non-metastasis of mediastinal lymph node and TNM stage of Ⅰ/Ⅱ (

0.05).The 1-year and 5-year survival rates of NSCLC patients were 83.33% and 52.63%

respectively

and the short-term and long-term survival rates in the MRD positive patients were lower than those in the MRD negative patients (

0.001).Low/undifferentiated tumor

tumor diameter

3 cm

TNM stage of ⅢA and postoperative MRD positive were all risk factors affecting the short-term and long-term survivals after NSCLC radical surgery (

0.05);besides

mediastinal lymph node metastases affected the long-term survival after NSCLC radical surgery (

0.05).The sensitivity

specificity and accuracy of postoperative MRD in predicting the short-term survival of NSCLC patients after radical surgery were 73.68%

89.47% and 76.32% respectively

and the sensitivity

specificity and accuracy of postoperative MRD in predicting the long-term survival were 95.00%

72.22% and 84.21% respectively.

Conclusion

The positive of MRD in NSCLC patients is related to the degree of tumor differentiation

TNM stage

tumor size

which is a risk factor that affects the short-term and long-term survival after NSCLC radical surgery

and has an important value for the prediction of short-term and long-term survivals.

关键词

非小细胞肺癌循环肿瘤DNA分子残留病灶根治术生存

Keywords

non-small cell lung cancercirculating tumor DNAminimal residual diseaseradical surgerysurvival

references

Sung H，Ferlay J，Siegel RL，et al.Global cancer statistics 2020：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin，2021，71（3）：209-249.doi：10.3322/caac.21660http://dx.doi.org/10.3322/caac.21660.

Weckler BC，Baldes N，Schirren J.Survival following multimodality treatment including surgery for stage ⅠA-ⅢB small-cell lung cancer［J］.Thorac Cardiovasc Surg，2019，67（4）：291-298.doi：10.1055/s-0038-1667145http://dx.doi.org/10.1055/s-0038-1667145.

Evison M，Barrett E，Cheng A，et al.Predicting the risk of disease recurrence and death following curative-intent radiotherapy for non-small cell lung cancer：the development and validation of two scoring systems from a large multicentre UK cohort［J］.Clin Oncol （R CollRadiol），2021，33（3）：145-154.doi：10.1016/j.clon.2020.09.001http://dx.doi.org/10.1016/j.clon.2020.09.001.

Li J，Dong W，Liu LN，et al.Liquid biopsy for ALK-positive early non-small-cell lung cancer predicts disease relapse［J］.Future Oncol，2021，17（1）：81-90.doi：10.2217/fon-2020-0554http://dx.doi.org/10.2217/fon-2020-0554.

Benetton M，Merli P，Walter C，et al.Molecular measurable residual disease assessment before hematopoietic stem cell transplantation in pediatric acute myeloid leukemia patients：a retrospective study by the I-BFM study group［J］.Biomedicines，2022，10（7）：1530.doi：10.3390/biomedicines10071530http://dx.doi.org/10.3390/biomedicines10071530.

Xie H，Kim RD.The application of circulating tumor DNA in the screening，surveillance，and treatment monitoring of colorectal cancer［J］.Ann Surg Oncol，2021，28（3）：1845-1858.doi：10.1245/s10434-020-09002-7http://dx.doi.org/10.1245/s10434-020-09002-7.

Magbanua MJM，Swigart LB，Wu HT，et al.Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival［J］.Ann Oncol，2021，32（2）：229-239.doi：10.1016/j.annonc. 2020.11.007http://dx.doi.org/10.1016/j.annonc.2020.11.007.

吴一龙，陆舜，程颖，等.非小细胞肺癌分子残留病灶专家共识［J］.循证医学，2021，21（3）：129-135.doi：10.12019/j.issn.1671-5144.2021.03.001http://dx.doi.org/10.12019/j.issn.1671-5144.2021.03.001.

赵健，刘利群，艾飞玲，等.中国2013—2018年≥30岁居民肺癌死亡率变化轨迹分析［J］.中国公共卫生，2021，37（10）：1495-1500.doi：10.11847/zgggws1132799http://dx.doi.org/10.11847/zgggws1132799.

朱李茹，华影，唐晓磊.自组装发光定量系统检测胆囊癌患者血清循环游离DNA的水平变化及意义［J］.山东医药，2021，26（1）：25-28.doi：10.3969/j.issn.1002-266X.2021.01.006http://dx.doi.org/10.3969/j.issn.1002-266X.2021.01.006.

Bratman SV，Yang SYC，Iafolla MAJ，et al.Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab［J］.Nat Cancer，2020，1（9）：873-881.doi：10.1038/s43018-020-0096-5http://dx.doi.org/10.1038/s43018-020-0096-5.

Parikh AR，Van Seventer EE，Siravegna G，et al.Minimal residual disease detection using a plasma-only circulating tumor DNA assay in patients with colorectal cancer［J］.Clin Cancer Res，2021，27（20）：5586-5594.doi：10.1158/1078-0432.CCR-21-0410http://dx.doi.org/10.1158/1078-0432.CCR-21-0410.

Yang J，Gong Y，Lam VK，et al.Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer［J］.Cell Death Dis，2020，11（5）：346.doi：10.1038/s41419-020-2531-zhttp://dx.doi.org/10.1038/s41419-020-2531-z.

Hata T，Mizuma M，Iseki M，et al.Circulating tumor DNA as a predictive marker for occult metastases in pancreatic cancer patients with radiographically non-metastatic disease［J］.J Hepatobiliary Pancreat Sci，2021，28（8）：648-658.doi：10.1002/jhbp.993http://dx.doi.org/10.1002/jhbp.993.

郭丽，高伟，袁秋月，等.血浆循环肿瘤DNA与宫颈癌临床病理特征的相关性分析［J］.医学分子生物学杂志，2021，18（5）：349-353.doi：10.3870/j.issn.1672-8009.2021.05.005http://dx.doi.org/10.3870/j.issn.1672-8009.2021.05.005.

Chin RI，Chen K，Usmani A，et al.Detection of solid tumor molecular residual disease （MRD） using circulating tumor DNA （ctDNA）［J］.Mol Diagn Ther，2019，23（3）：311-331.doi：10.1007/s40291-019-00390-5http://dx.doi.org/10.1007/s40291-019-00390-5.

Eisinger S，Sarhan D，Boura VF，et al.Targeting a scavenger receptor on tumor-associated macrophages activates tumor cell killing by natural killer cells［J］.Proc Natl Acad Sci USA，2020，117（50）：32005-32016.doi：10.1073/pnas.2015343117http://dx.doi.org/10.1073/pnas.2015343117.

Tie J，Cohen JD，Wang Y，et al.Circulating tumor DNA analyses as markers of recurrence risk and benefit of adjuvant therapy for stage Ⅲ colon cancer［J］.JAMA Oncol，2019，5（12）：1710-1717.doi：10.1001/jamaoncol.2019.3616http://dx.doi.org/10.1001/jamaoncol.2019.3616.

Chaudhuri AA，Chabon JJ，Lovejoy AF，et al.Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling［J］.Cancer Discov，2017，7（12）：1394-1403.doi：10.1158/2159-8290.CD-17-0716http://dx.doi.org/10.1158/2159-8290.CD-17-0716.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mechanism of circAGFG1 on biological behavior of non-small cell lung cancer

Expression and biological role of DCST1-AS1 in non-small cell lung cancer

Exosome miR-20a-5p regulates Sp1/CD147 signaling pathway to promote bone metastasis in non-small cell lung cancer

Analysis on influencing factors of concurrent free anterolateral femoral skin flap repair in radical operation for oral cancer

Effects of miR-195 suppresses proliferation,metastasis and invasion on non-small cell lung cancer cells by targeting CHEK1

Related Author

LI Xiao-yuan

YANG Yan-jun

DONG Yue-hua

GAO Yong-shan

JIANG Wei-hua

WANG Gui-gang

WANG Da-wei

WEI Yu-lei

Related Institution

Department of Thoracic Surgery， the First Affiliated Hospital of Hebei North University

Department of Pathology， Baoding Second Hospital

Department of Pharmacy， Baoding Second Hospital

Department of Oncology， Second Affiliated Hospital of Air Force Medical University

Department of Stomatology,Affiliated Hospital of Guangdong Medical College

⁰