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Tumor Biology
Published in: Tumor Biology 1/2015

01-01-2015 | Review

Cell-free circulating tumor DNA in plasma/serum of non-small cell lung cancer

Authors: Kun Nie, Yujie Jia, Xuezhu Zhang

Published in: Tumor Biology | Issue 1/2015

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Abstract

Non-small cell lung cancer (NSCLC) is the common type of lung cancer, which is the leading cause of cancer death throughout the world. Most patients were diagnosed too late for curative treatment. So, it is necessary to develop a minimal invasive method to identify NSCLC at an early stage. In recent years, cell-free circulating tumor DNA (ctDNA) has attracted increasing attention as a potential tumor marker for its minimal invasive, convenient, and easily accepted properties. The amount of ctDNA in plasma or serum was significantly higher in NSCLC patients than that in healthy controls or patients with benign diseases. Furthermore, many studies have proved an association among tumor stage, tumor grade, lymph node involvement, the number of metastatic sites, tumor response, survival outcome, and the ctDNA levels. Many genetic changes, such as gene mutation, loss of heterozygosity, microsatellite instability, and gene methylation were also found in ctDNA in NSCLC patients. These findings demonstrated that the ctDNA could serve as a viable tool to monitor NSCLC and prompted us to find more sensitive and specific biomarkers for clinical practice, especially monitor these cases with at least one known gene abnormality. Here, we reviewed the evidence of ctDNA in NSCLC and consider possible future applications in patient management.
Literature
1.
Society AC. Cancer facts and figures. 2012.
2.
3.
Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biogeosciences. 2009;3:215–24.
4.
Agarwal M et al. Age, tumor size, type of surgery, and gender predict survival in early stage (stage I and II) non-small cell lung cancer after surgical resection. Lung Cancer. 2010;68(3):398–402.PubMedCrossRef
5.
6.
7.
Diaz Jr LA et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature. 2012;486(7404):537–40.PubMedPubMedCentral
8.
Lee YJ et al. Circulating cell-free DNA in plasma of never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as first-line therapy. Clin Cancer Res. 2011;17(15):5179–87.PubMedCrossRef
9.
Pan S et al. Can plasma DNA monitoring be employed in personalized chemotherapy for patients with advanced lung cancer? Biomed Pharmacother. 2012;66(2):131–7.PubMedCrossRef
10.
Szpechcinski A et al. Quantitative analysis of free-circulating DNA in plasma of patients with resectable NSCLC. Expert Opin Biol Ther. 2012;12 Suppl 1:S3–9.PubMedCrossRef
11.
12.
Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11(6):426–37.PubMedCrossRef
13.
Viorritto IC, Nikolov NP, Siegel RM. Autoimmunity versus tolerance: can dying cells tip the balance? Clin Immunol. 2007;122(2):125–34.PubMedCrossRef
14.
Fleischhacker M, Schmidt B. Cell-free DNA resuscitated for tumor testing. Nat Med. 2008;14(9):914–5.PubMedCrossRef
15.
Bendich A, Wilczok T, Borenfreund E. Circulating DNA as a possible factor in oncogenesis. Science. 1965;148(3668):374–6.PubMedCrossRef
16.
Leon SA et al. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res. 1977;37(3):646–50.PubMed
17.
Kumar S et al. Plasma DNA level in predicting therapeutic efficacy in advanced nonsmall cell lung cancer. Eur Respir J. 2010;36(4):885–92.PubMedCrossRef
18.
Sirera R et al. Can serum be used for analyzing the EGFR mutation status in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2011;6(2):286–90.PubMedCrossRef
19.
Vinayanuwattikun C et al. The impact of non-tumor-derived circulating nucleic acids implicates the prognosis of non-small cell lung cancer. J Cancer Res Clin Oncol. 2013;139(1):67–76.PubMedCrossRef
20.
Ludovini V et al. Plasma DNA, microsatellite alterations, and p53 tumor mutations are associated with disease-free survival in radically resected non-small cell lung cancer patients: a study of the perugia multidisciplinary team for thoracic oncology. J Thorac Oncol. 2008;3(4):365–73.PubMedCrossRef
21.
22.
Szpechcinski A et al. Real-time PCR quantification of plasma DNA in non-small cell lung cancer patients and healthy controls. Eur J Med Res. 2009;14 Suppl 4:237–40.PubMedPubMedCentralCrossRef
23.
Paci M et al. Circulating plasma DNA as diagnostic biomarker in non-small cell lung cancer. Lung Cancer. 2009;64(1):92–7.PubMedCrossRef
24.
Roth C et al. Screening for circulating nucleic acids and caspase activity in the peripheral blood as potential diagnostic tools in lung cancer. Mol Oncol. 2011;5(3):281–91.PubMedCrossRef
25.
Camps C et al. The identification of KRAS mutations at codon 12 in plasma DNA is not a prognostic factor in advanced non-small cell lung cancer patients. Lung Cancer. 2011;72(3):365–9.PubMedCrossRef
26.
Jian G et al. Prediction of epidermal growth factor receptor mutations in the plasma/pleural effusion to efficacy of gefitinib treatment in advanced non-small cell lung cancer. J Cancer Res Clin Oncol. 2010;136(9):1341–7.PubMedCrossRef
27.
He C et al. Detection of epidermal growth factor receptor mutations in plasma by mutant-enriched PCR assay for prediction of the response to gefitinib in patients with non-small-cell lung cancer. Int J Cancer. 2009;125(10):2393–9.PubMedCrossRef
28.
Zhang L et al. Detection of EGFR somatic mutations in non-small cell lung cancer (NSCLC) using a novel mutant-enriched liquidchip (MEL) technology. Curr Drug Metab. 2012;13(7):1007–11.PubMedCrossRef
29.
Zhao X et al. Comparison of epidermal growth factor receptor mutation statuses in tissue and plasma in stage I–IV non-small cell lung cancer patients. Respiration. 2013;85(2):119–25.PubMedCrossRef
30.
Kimura H et al. EGFR mutation of tumor and serum in gefitinib-treated patients with chemotherapy-naive non-small cell lung cancer. J Thorac Oncol. 2006;1(3):260–7.PubMedCrossRef
31.
Wang S et al. Potential clinical significance of a plasma-based KRAS mutation analysis in patients with advanced non-small cell lung cancer. Clin Cancer Res. 2010;16(4):1324–30.PubMedCrossRef
32.
Nygaard AD et al. The prognostic value of KRAS mutated plasma DNA in advanced non-small cell lung cancer. Lung Cancer. 2013;79(3):312–7.PubMedCrossRef
33.
Kim ST et al. Can serum be used for analyzing the EGFR mutation status in patients with advanced non-small cell lung cancer? Am J Clin Oncol. 2013;36(1):57–63.PubMedCrossRef
34.
Bai H et al. Epidermal growth factor receptor mutations in plasma DNA samples predict tumor response in Chinese patients with stages IIIB to IV non-small-cell lung cancer. J Clin Oncol. 2009;27(16):2653–9.PubMedCrossRef
35.
Yung TK et al. Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung cancer patients. Clin Cancer Res. 2009;15(6):2076–84.PubMedCrossRef
36.
Narayan A et al. Ultrasensitive measurement of hotspot mutations in tumor DNA in blood using error-suppressed multiplexed deep sequencing. Cancer Res. 2012;72(14):3492–8.PubMedPubMedCentralCrossRef
37.
Angulo B et al. A comparison of EGFR mutation testing methods in lung carcinoma: direct sequencing, real-time PCR and immunohistochemistry. PLoS One. 2012;7(8):e43842.PubMedPubMedCentralCrossRef
38.
Sheffield VC et al. The sensitivity of single-strand conformation polymorphism analysis for the detection of single base substitutions. Genomics. 1993;16(2):325–32.PubMedCrossRef
39.
Cohen V et al. Evaluation of denaturing high-performance liquid chromatography as a rapid detection method for identification of epidermal growth factor receptor mutations in nonsmall-cell lung cancer. Cancer. 2006;107(12):2858–65.PubMedCrossRef
40.
41.
Lynch TJ et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129–39.PubMedCrossRef
42.
Paez JG et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497–500.PubMedCrossRef
43.
44.
Mack PC et al. EGFR mutations detected in plasma are associated with patient outcomes in erlotinib plus docetaxel-treated non-small cell lung cancer. J Thorac Oncol. 2009;4(12):1466–72.PubMedCrossRef
45.
Punnoose EA et al. Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res. 2012;18(8):2391–401.PubMedCrossRef
46.
Tsao DA et al. A fast and convenient new technique to detect the therapeutic target, K-ras mutant, from peripheral blood in non-small cell lung cancer patients. Lung Cancer. 2010;68(1):51–7.PubMedCrossRef
47.
Salazar F et al. First-line therapy and methylation status of CHFR in serum influence outcome to chemotherapy versus EGFR tyrosine kinase inhibitors as second-line therapy in stage IV non-small-cell lung cancer patients. Lung Cancer. 2011;72(1):84–91.PubMedCrossRef
48.
Kuang Y et al. Noninvasive detection of EGFR T790M in gefitinib or erlotinib resistant non-small cell lung cancer. Clin Cancer Res. 2009;15(8):2630–6.PubMedPubMedCentralCrossRef
49.
Kimura H et al. Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA). Br J Cancer. 2007;97(6):778–84.PubMedPubMedCentralCrossRef
50.
Kimura H et al. Detection of epidermal growth factor receptor mutations in serum as a predictor of the response to gefitinib in patients with non-small-cell lung cancer. Clin Cancer Res. 2006;12(13):3915–21.PubMedCrossRef
51.
Goto K et al. Epidermal growth factor receptor mutation status in circulating free DNA in serum: from IPASS, a phase III study of gefitinib or carboplatin/paclitaxel in non-small cell lung cancer. J Thorac Oncol. 2012;7(1):115–21.PubMedCrossRef
52.
Isobe K et al. Clinical significance of circulating tumor cells and free DNA in non-small cell lung cancer. Anticancer Res. 2012;32(8):3339–44.PubMed
53.
Nakamura T et al. Application of a highly sensitive detection system for epidermal growth factor receptor mutations in plasma DNA. J Thorac Oncol. 2012;7(9):1369–81.PubMedCrossRef
54.
Brevet M et al. Detection of EGFR mutations in plasma DNA from lung cancer patients by mass spectrometry genotyping is predictive of tumor EGFR status and response to EGFR inhibitors. Lung Cancer. 2011;73(1):96–102.PubMedCrossRef
55.
Jiang B et al. Serum detection of epidermal growth factor receptor gene mutations using mutant-enriched sequencing in Chinese patients with advanced non-small cell lung cancer. J Int Med Res. 2011;39(4):1392–401.PubMedCrossRef
56.
57.
Janne PA. Challenges of detecting EGFR T790M in gefitinib/erlotinib-resistant tumours. Lung Cancer. 2008;60 Suppl 2:S3–9.PubMedCrossRef
58.
Pao W et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2005;2(3):e73.PubMedPubMedCentralCrossRef
59.
Suda K et al. EGFR T790M mutation: a double role in lung cancer cell survival? J Thorac Oncol. 2009;4(1):1–4.PubMedCrossRef
60.
Ma C, Wei S, Song Y. T790M and acquired resistance of EGFR TKI: a literature review of clinical reports. J Thorac Dis. 2011;3(1):10–8.PubMedPubMedCentral
61.
Inukai M et al. Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res. 2006;66(16):7854–8.PubMedCrossRef
62.
Kris MG, Simon GR. Maintenance therapy for non-small cell lung cancer. The NCCN 15th Annual Conference: Clinical Practice Guidelines & Quality Cancer Care. 2010.
63.
64.
Califano R, Landi L, Cappuzzo F. Prognostic and predictive value of K-RAS mutations in non-small cell lung cancer. Drugs. 2012;72 Suppl 1:28–36.PubMedCrossRef
65.
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Non-Small Cell Lung Cancer V2. 2012.
66.
Keedy VL et al. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol. 2011;29(15):2121–7.PubMedCrossRef
67.
Carpagnano GE et al. 3p microsatellite signature in exhaled breath condensate and tumor tissue of patients with lung cancer. Am J Respir Crit Care Med. 2008;177(3):337–41.PubMedCrossRef
68.
Sirera R et al. Retrospective analysis of the prognostic role of p16 protein inactivation in plasma in patients with locally advanced non-small cell lung cancer. Lung Cancer. 2008;61(1):104–8.PubMedCrossRef
69.
70.
Speicher MR. Microsatellite instability in human cancer. Oncol Res. 1995;7(6):267–75.PubMed
71.
Silva JM, Bonilla F, Correspondence re: Coulet F et al. Detection of plasma tumor DNA in head and neck squamous cell carcinoma by microsatellite typing and p53 mutation analysis. Cancer Res. 2000;60:707–9. Cancer Res. 2001;61(23):8595–6.
72.
Esteller M. CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene. 2002;21(35):5427–40.PubMedCrossRef
73.
Zhang Y et al. Methylation of multiple genes as a candidate biomarker in non-small cell lung cancer. Cancer Lett. 2011;303(1):21–8.PubMedCrossRef
74.
Fischer JR et al. Prognostic significance of RASSF1A promoter methylation on survival of non-small cell lung cancer patients treated with gemcitabine. Lung Cancer. 2007;56(1):115–23.PubMedCrossRef
75.
Lee SM, Park JY, Kim DS. Methylation of TMEFF2 gene in tissue and serum DNA from patients with non-small cell lung cancer. Mol Cells. 2012;34(2):171–6.PubMedPubMedCentralCrossRef
76.
Ponomaryova AA et al. RARbeta2 gene methylation level in the circulating DNA from blood of patients with lung cancer. Eur J Cancer Prev. 2011;20(6):453–5.PubMedCrossRef
77.
Vinayanuwattikun C et al. Epithelial-specific methylation marker: a potential plasma biomarker in advanced non-small cell lung cancer. J Thorac Oncol. 2011;6(11):1818–25.PubMedCrossRef
78.
Zhang Y et al. Frequent epigenetic inactivation of deleted in lung and esophageal cancer 1 gene by promoter methylation in non-small-cell lung cancer. Clin Lung Cancer. 2010;11(4):264–70.PubMedCrossRef
79.
Zhang YW et al. Transcriptional inactivation of secreted frizzled-related protein 1 by promoter hypermethylation as a potential biomarker for non-small cell lung cancer. Neoplasma. 2010;57(3):228–33.PubMedCrossRef
80.
Hoffmann AC et al. Lack of prognostic significance of serum DNA methylation of DAPK, MGMT, and GSTPI in patients with non-small cell lung cancer. J Surg Oncol. 2009;100(5):414–7.PubMedCrossRef
81.
Zhang Y et al. Frequent transcriptional inactivation of Kallikrein 10 gene by CpG island hypermethylation in non-small cell lung cancer. Cancer Sci. 2010;101(4):934–40.PubMedCrossRef
82.
Hoffmann AC et al. Methylated DAPK and APC promoter DNA detection in peripheral blood is significantly associated with apparent residual tumor and outcome. J Cancer Res Clin Oncol. 2009;135(9):1231–7.PubMedCrossRef
Metadata
Title
Cell-free circulating tumor DNA in plasma/serum of non-small cell lung cancer
Authors
Kun Nie
Yujie Jia
Xuezhu Zhang
Publication date
01-01-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 1/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2758-3

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