Keywords
How to Cite
Abstract
«Liquid biopsy» is gradually becoming a mandatory procedure in cancer diagnostics. The aim of this procedure is to detect and monitor tumor-specific markers in various body fluids (blood, urine, pleural fluid, etc.). Significant efforts have been made to convert the most common mutational tests (EGFR, KRAS, BRAF) into non-invasive procedures. Despite some advantages, “liquid biopsy” is still not equivalent to traditional tissue analysis due to limited sensitivity and specificity; it cannot be routinely used in cancer medicine until the standardization of pre-analytical procedures is agreed. We intend to improve the performance of liquid biopsy for detection of a number of clinically relevant mutations (EGFR: ex19del and L858R; KRAS: 12, 13, 61, 146 codon nucleotide substitutions; BRAF: V600E). 417 plasma samples obtained from 88 patients (KRAS/NRAS/BRAF-mutated colorectal cancer (CRC): n= 57; EGFR-mutated lung adenocarcinomas (LC): n = 14; BRAF-mutated melanoma: n = 17) were analyzed by ddPCR for the presence of corresponding mutations in the circulating tumor DNA (ctDNA). Presence of tumor-specific mutations in plasma was confirmed in 32/57 (56%) CRC, 7/14 (50%) LC, and 4/17 (24%) melanoma cases. The proportion of mutation-positive plasma cases was tended to be higher in the group of patients with distant metastases compared to subjects with localized disease [34/56 (61%) vs. 5/15 (33%), р = 0.058]. 86 patients provided their blood at 9.00 (morning) and at 16.00 (afternoon). In addition, blood-takes were performed before and 15 minutes after usual breakfast as well as before and 15 minutes after moderate physical exercise. The detection rate of cancer-specific mutations in plasma was not significantly correlated with described above circumstances of blood-take. Meanwhile, the noticeable intrapatient variability of circulating mutation success rate has been detected. Thus, depending on clinical circumstances, at least negative ctDNA tests could be advised to be repeated in some patients, in order to ensure the reliability of results.
References
Abbosh C., Birkbak N.J., Wilson G.A. et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution // Nature. - 2017. - Vol. 545. - P 446-451.
Atamaniuk J., Vidotto C., Tschan H. et al. Increased concentrations of cell-free plasma DNA after exhaustive exercise // Clin Chem. - 2004. - Vol. 50. - № 9. - P. 1668-1670.
Breitbach S., Tug S., Simon P Circulating cell-free DNA: an up-coming molecular marker in exercise physiology // Sports Med. - 2012. - Vol. 42. - № 7. - P 565-586.
Calapre L., Giardina T., Robinson C. et al. Locus-specific concordance of genomic alterations between tissue and plasma circulating tumor DNA in metastatic melanoma // Mol Oncol. - 2018. - Vol. 13. - № 2. - P 171-184.
Chan K.C., Yeung S.W., Lui W.B. et al. Effects of preana-lytical factors on the molecular size of cell-free DNA in blood // Clin Chem. - 2005. - Vol. 51. - P 781-784.
Diefenbach R.J., Lee J.H., Kefford R.F., Rizos H. Evaluation of commercial kits for purification of circulating free DNA // Cancer Genet. - 2018. - Vol. 228. - P. 21-27.
Diehl F, Schmidt K., Choti M.A. et al. Circulating mutant DNA to assess tumor dynamics // Nat Med. - 2008. - Vol. 14. - P 985-990.
Dierickx P., Van Laake L.W., Geijsen N. Circadian clocks: from stem cells to tissue homeostasis and regeneration // EMBO Rep. - 2018. - Vol. 19. - P 18-28.
El Messaoudi S., Mouliere F, Du Manoir S. et al. Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care // Clin Cancer Res. - 2016. - Vol. 22. - № 12. - P. 3067-3077.
Galot R., van Marcke C., Helaers R. et al. Liquid biopsy for mutational profiling of locoregional recurrent and/or metastatic head and neck squamous cell carcinoma // Oral Oncol. - 2020. - Vol. 104. - P 104631.
Guo Q., Wang J., Xiao J. et al. Heterogeneous mutation pattern in tumor tissue and circulating tumor DNA warrants parallel NGS panel testing // Mol Cancer. - 2018. - Vol. 17. - № 1. - P. 131.
Haselmann V., Ahmad-Nejad P., Geilenkeuser W.J. et al. Results of the first external quality assessment scheme (EQA) for isolation and analysis of circulating tumour DNA (ctDNA) // Clin Chem Lab Med. - 2018. - Vol. 56. - № 2. - P. 220-228.
Jung M., Klotzek S., Lewandowski M. et al. Changes in concentration of DNA in serum and plasma during storage of blood samples // Clin Chem. - 2003. -Vol. 49. - P. 1028-1029.
Lee J.S., Kim M., Seong M.W. et al. Plasma vs. serum in circulating tumor DNA measurement: characterization by DNA fragment sizing and digital droplet polymerase chain reaction // Clin Chem Lab Med. - 2020. - Vol. 58. - P. 527-532.
Ma F, Guan Y, Yi Z., Chang L. et al. Assessing tumor heterogeneity using ctDNA to predict and monitor therapeutic response in metastatic breast cancer // Int J Cancer. - 2020. - Vol. 146. - № 5. - P 1359-1368.
Madic J., Kiialainen A., Bidard F-C. et al. (2015), Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients // Int. J. Cancer. - 2015. - Vol. 136. - P 2158-2165.
Markus H., Contente-Cuomo T, Farooq M. et al. Evaluation of pre-analytical factors affecting plasma DNA analysis // Sci Rep. - 2018. - Vol. 8. - № 1. - P. 7375.
Meddeb R., Dache Z.A.A., Thezenas S. et al. Quantifying circulating cell-free DNA in humans // Sci Rep. - 2019. - Vol. 9. - № 1. - P 5220.
Nikolaev S., Lemmens L., Koessler T. et al. Circulating tumoral DNA: Preanalytical validation and quality control in a diagnostic laboratory // Anal Biochem. - 2018. - Vol. 542. - P. 34-39.
Osumi H., Shinozaki E., Takeda Y et al. Clinical relevance of circulating tumor DNA assessed through deep sequencing in patients with metastatic colorectal cancer // Cancer Med. - 2019. - Vol. 8. - № 1. - P. 408-417.
Parpart-Li S., Bartlett B., Popoli M. et al. The Effect of Preservative and Temperature on the Analysis of Circulating Tumor DNA // Clin Cancer Res. - 2017. - Vol. 23. - P 2471-2477.
Parsons H.A., Rhoades J., Reed S.C. et al. Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer // Clin Cancer Res. - 2020.
Reece M., Saluja H., Hollington P. et al. The Use of Circulating Tumor DNA to Monitor and Predict Response to Treatment in Colorectal Cancer // Front Genet. - 2019. - Vol. 10. - P. 1118.
Siravegna G., Mussolin B., Buscarino M. et al. Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients // Nat Med. - 2015. - Vol. 21. - P. 795-801.
Sorber L, Zwaenepoel K, Jacobs J, et al. Circulating Cell-Free DNA and RNA Analysis as Liquid Biopsy: Optimal Centrifugation Protocol // Cancers (Basel). - 2019. - Vol. 11. - № 4. - P. 458.
Spindler K.L., Pallisgaard N., Appelt A.L. et al. Clinical utility of KRAS status in circulating plasma DNA compared to archival tumour tissue from patients with metastatic colorectal cancer treated with anti epidermal growth factor receptor therapy // Eur J Cancer. - 2015. - Vol. 51. - P. 2678-2685.
Tth K., Patai.V., Kalmr A. et al. Circadian Rhythm of Methylated Septin 9, Cell-Free DNA Amount and Tumor Markers in Colorectal Cancer Patients // Pathol Oncol Res. - 2017. - Vol. 23. - P. 699-706.
Tug S., Tross A.K., Hegen P. et al. Acute effects of strength exercises and effects of regular strength training on cell free DNA concentrations in blood plasma // PLoS One. - 2017. - Vol. 12. - № 9. - P. e0184668.
Vall e A., Marcq M., Bizieux A. et al. Plasma is a better source of tumor-derived circulating cell-free DNA than serum for the detection of EGFR alterations in lung tumor patients // Lung Cancer. - 2013. - Vol. 82. - P 373-374.
van Ginkel J.H., van den Broek D.A., van Kuik J. et al. Preanalytical blood sample workup for cell-free DNA analysis using Droplet Digital PCR for future molecular cancer diagnostics // Cancer Med. - 2017. - Vol. 6. - № 10. - P 2297-2307.
Vidal J., Muinelo L., Dalmases A. et al. Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients // Ann Oncol. - 2017. - Vol. 28. - P 1325 1332.
Vrabel D., Sedlarikova L., Besse L. et al. Dynamics of tumor-specific cfDNA in response to therapy in multiple myeloma patients // Eur J Haematol. - 2020. - Vol. 104. - № 3. - P 190-197.
Wu X., Li J., Gassa A., Buchner D. et al. Circulating tumor DNA as an emerging liquid biopsy biomarker for early diagnosis and therapeutic monitoring in hepatocellular carcinoma // Int J Biol Sci. - 2020. - Vol. 16. - № 9. - P. 1551-1562.
Xie W., Xie L., Song X. The diagnostic accuracy of circulating free DNA for the detection of KRAS mutation status in colorectal cancer: A meta-analysis // Cancer Med. - 2019. - Vol. 8. - № 3. - P 1218-1231.
Yi X., Ma J., Guan Y et al. The feasibility of using mutation detection in ctDNA to assess tumor dynamics // Int J Cancer. - 2017. - Vol. 140. - № 12. - P 2642-2647.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
© АННМО «Вопросы онкологии», Copyright (c) 2020