Preoperative Mutational Analysis of Circulating Tumor Cells (CTCs) and Plasma-cfDNA Provides Complementary Information for Early Prediction of Relapse: A Pilot Study in Early-Stage Non-Small Cell Lung Cancer

We assessed whether preoperativemutational analyses of circulating tumor cells (CTCs) and plasma-cfDNA could be used as minimally invasive biomarkers and as complimentary tools for early prediction of relapse in early-stage non-small -cell lung cancer (NSCLC). Using ddPCR assays, hotspot mutations o...

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Bibliographic Details
Published in:	Cancers Vol. 15; no. 6; p. 1877
Main Authors:	Markou, A N, Londra, D, Stergiopoulou, D, Vamvakaris, I, Potaris, K, Pateras, I S, Kotsakis, A, Georgoulias, V, Lianidou, E
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 21-03-2023 MDPI
Subjects:	Biomarkers Biopsy Cancer Cancer cells Cancer therapies Care and treatment Clinical trials Deoxyribonucleic acid DNA Epidermal growth factor receptors Genetic aspects Genomes Genomics Health aspects Hospitals K-Ras protein Lung cancer Lung cancer, Non-small cell Lymphatic system Medical imaging Mutation Mutation (Biology) Mutation hot spots Non-small cell lung carcinoma Patients Plasma Prognosis Relapse Small cell lung carcinoma Surgery Thoracic surgery Tumor cells Tumors Greece United States > US Germany mutations NSCLC relapse cfDNA CTCs MRD liquid biopsy
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Summary:	We assessed whether preoperativemutational analyses of circulating tumor cells (CTCs) and plasma-cfDNA could be used as minimally invasive biomarkers and as complimentary tools for early prediction of relapse in early-stage non-small -cell lung cancer (NSCLC). Using ddPCR assays, hotspot mutations of and were identified in plasma-cfDNA samples and size-based enriched CTCs isolated from the same blood samples of 49 early-stage NSCLC patients before surgery and in a control group of healthy blood donors ( = 22). Direct concordance of the mutational spectrum was further evaluated in 27 patient-matched plasma-cfDNA and CTC-derived DNA in comparison to tissue-derived DNA. The prevalence of detectable mutations of the four tested genes was higher in CTC-derived DNA than in the corresponding plasma-cfDNA (38.8% and 24.5%, respectively).The most commonly mutated gene was PIK3CA, in both CTCs and plasma-cfDNA at baseline and at the time of relapse. Direct comparison of the mutation status of selected drug-responsive genes in CTC-derived DNA, corresponding plasma-cfDNA and paired primary FFPE tissues clearly showed the impact of heterogeneity both within a sample type, as well as between different sample components. The incidence of relapse was higher when at least one mutation was detected in CTC-derived DNA or plasma-cfDNA compared with patients in whom no mutation was detected ( =0.023). Univariate analysis showed a significantly higher risk of progression (HR: 2.716; 95% CI, 1.030-7.165; =0.043) in patients with detectable mutations in plasma-cfDNA compared with patients with undetectable mutations, whereas the hazard ratio was higher when at least one mutation was detected in CTC-derived DNA or plasma-cfDNA (HR: 3.375; 95% CI, 1.098-10.375; =0.034). Simultaneous mutational analyses of plasma-cfDNA and CTC-derived DNA provided complementary molecular information from the same blood sample and greater diversity in genomic information for cancer treatment and prognosis. The detection of specific mutations in ctDNA and CTCs in patients with early-stage NSCLC before surgery was independently associated with disease recurrence, which represents an important stratification factor for future trials.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2072-6694 2072-6694
DOI:	10.3390/cancers15061877