Detection of EGFR Mutations in cfDNA and CTCs, and Comparison to Tumor Tissue in Non-Small-Cell-Lung-Cancer (NSCLC) Patients

被引:38
作者
Liu, Haiyan E. [1 ]
Vuppalapaty, Meghah [1 ]
Wilkerson, Charles [1 ]
Renier, Corinne [1 ]
Chiu, Michael [1 ]
Lemaire, Clementine [1 ]
Che, James [1 ]
Matsumoto, Melissa [2 ]
Carroll, James [3 ]
Crouse, Steve [1 ]
Hanft, Violet R. [4 ]
Jeffrey, Stefanie S. [4 ]
Di Carlo, Dino [2 ,5 ,6 ]
Garon, Edward B. [3 ,6 ]
Goldman, Jonathan [3 ,6 ]
Sollier, Elodie [1 ]
机构
[1] Vortex Biosci Inc, Pleasanton, CA 94588 USA
[2] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA
[4] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA
[5] Calif NanoSyst Inst, Los Angeles, CA USA
[6] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA
来源
FRONTIERS IN ONCOLOGY | 2020年 / 10卷
关键词
Vortex technology; circulating tumor cell; total liquid biopsy; epidermal grow factor receptor; EGFR mutation analysis; Non-small cell carcinoma; circulating tumor biomarkers; circulating free DNA (cfDNA); LABEL-FREE ISOLATION; LIQUID BIOPSY; BLOOD;
D O I
10.3389/fonc.2020.572895
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Lung cancer is the leading cause of cancer-related mortality worldwide. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapies, based on the evaluation ofEGFRmutations, have shown dramatic clinical benefits.EGFRmutation assays are mainly performed on tumor biopsies, which carry risks, are not always successful and give results relevant to the timepoint of the assay. To detect secondaryEGFRmutations, which cause resistance to 1st and 2nd generation TKIs and lead to the administration of a 3rd generation drug, effective and non-invasive monitoring ofEGFRmutation status is needed. Liquid biopsy analytes, such as circulating tumor cells (CTCs) and circulating tumor DNA (cfDNA), allow such monitoring over the course of the therapy. The aim of this study was to develop and optimize a workflow for the evaluation of cfDNA and CTCs in NSCLC patients all from one blood sample. Using Vortex technology and EntroGen ctEGFR assay,EGFRmutations were identified at 0.5 ng of DNA (similar to 83 cells), with a sensitivity ranging from 0.1 to 2.0% for a total DNA varying from 25 ng (similar to 4 CTCs among 4000 white blood cells, WBCs) to 1 ng (similar to 4 CTCs among 200 WBCs). The processing of plasma-depleted-blood provided comparable capture recovery as whole blood, confirming the possibility of a multimodality liquid biopsy analysis (cfDNA and CTC DNA) from a single tube of blood. Different anticoagulants were evaluated and compared in terms of respective performance. Blood samples from 24 NSCLC patients and 6 age-matched healthy donors were analyzed with this combined workflow to minimize blood volume needed and sample-to-sample bias, and theEGFRmutation profile detected from CTCs and cfDNA was compared to matched tumor tissues. Despite the limited size of the patient cohort, results from this non-invasiveEGFRmutation analysis are encouraging and this combined workflow represents a valuable means for informing therapy selection and for monitoring treatment of patients with NSCLC.
引用
收藏
页数:14
相关论文
共 50 条
  • [21] Preservation of cfRNA in cytological supernatants for cfDNA & cfRNA double detection in non-small cell lung cancer patients
    Ma, Yidan
    Wang, Yifei
    He, Lei
    Du, Jun
    Li, Lin
    Bie, Zhixin
    Li, Yuanming
    Xu, Xiaomao
    Zhou, Wei
    Wu, Xiaonan
    Yang, Li
    Di, Jing
    Li, Chenyang
    Li, Xiaoguang
    Liu, Dongge
    Wang, Zheng
    [J]. CANCER MEDICINE, 2024, 13 (17):
  • [22] Detection of ALK Rearrangements in Non-Small-Cell Lung Cancer (NSCLC) Patients by Liquid Biopsy
    Lin, D.
    [J]. JOURNAL OF THORACIC ONCOLOGY, 2017, 12 (11) : S1862 - S1862
  • [23] Comparison of tissue-based and plasma-based testing for EGFR mutation in non-small cell lung cancer patients
    Kang, Yoon Kyung
    Shin, Dong Hoon
    Park, Joon Young
    Hwang, Chung Su
    Lee, Hyun Jung
    Lee, Jung Hee
    Kim, Jee Yeon
    Na, JooYoung
    [J]. JOURNAL OF PATHOLOGY AND TRANSLATIONAL MEDICINE, 2025, 59 (01) : 60 - 67
  • [24] Monitoring and Characterization of Circulating Tumor Cells (CTCs) in a Patient With EML4-ALK-Positive Non-Small Cell Lung Cancer (NSCLC)
    Aieta, Michele
    Facchinetti, Antonella
    De Faveri, Stefania
    Manicone, Mariangela
    Tartarone, Alfredo
    Possidente, Luciana
    Lerose, Rosa
    Mambella, Giuseppina
    Calderone, Giuseppe
    Zamarchi, Rita
    Rossi, Elisabetta
    [J]. CLINICAL LUNG CANCER, 2016, 17 (05) : E173 - E177
  • [25] A Case of Non-Small Cell Lung Cancer with Mutually Exclusive EGFR and KRAS Mutations
    Tushir, Abhimanyu
    Akhtar, Israh
    Seth, Anjali
    [J]. CURRENT ISSUES IN MOLECULAR BIOLOGY, 2025, 47 (01)
  • [26] The Impact of Liquid Biopsies Positive for EGFR Mutations on Overall Survival in Non-Small Cell Lung Cancer Patients
    Ruiz, Jonnathan Roldan
    Gago, Marta Gracia Fuentes
    Tabora, Luis Miguel Chinchilla
    Morais, Idalia Gonzalez
    Sayagues, Jose Maria
    Hernandez, Mar Abad
    Perez, Maria Rosa Cordovilla
    de la Cruz, Maria Dolores Ludena
    Morillo, Edel del Barco
    Gonzalez, Marta Rodriguez
    [J]. DIAGNOSTICS, 2023, 13 (14)
  • [27] A meta-analysis of liquid biopsy versus tumor histology for detecting EGFR mutations in non-small cell lung cancer
    Cai, Jing
    Wang, Wanning
    Zhang, Wenlong
    [J]. TRANSLATIONAL ONCOLOGY, 2024, 47
  • [28] Evaluation of Two EGFR Mutation Tests on Tumor and Plasma from Patients with Non-Small Cell Lung Cancer
    Kim, Jeong-Oh
    Shin, Jung-Young
    Kim, Seo Ree
    Shin, Kab Soo
    Kim, Joori
    Kim, Min-Young
    Lee, Mi-Ran
    Kim, Yonggoo
    Kim, Myungshin
    Hong, Sook Hee
    Kang, Jin Hyoung
    [J]. CANCERS, 2020, 12 (04)
  • [29] Role of Circulating Tumor DNA Profiling in Patients with Non-Small Cell Lung Cancer Treated with EGFR Inhibitor
    Ku, Bo Mi
    Kim, Yeon Jeong
    Park, Donghyun
    Lee, Se-Hoon
    Ahn, Jin Seok
    Park, Keunchil
    Ahn, Myung-Ju
    Sun, Jong-Mu
    [J]. ONCOLOGY, 2022, 100 (04) : 228 - 237
  • [30] Urine test for EGFR analysis in patients with non-small cell lung cancer
    Franovic, Aleksandra
    Raymond, Victoria M.
    Erlander, Mark G.
    Reckamp, Karen L.
    [J]. JOURNAL OF THORACIC DISEASE, 2017, 9 : S1323 - S1331