The Evaluation of Circulating Tumor DNA and Carcinoembryonic Antigen Levels and Relationship with Clinicopathological Risk Factors and Prognostic Indices in Colorectal Cancer Patients

ctDNA and CEA Relationship in Colorectal Cancer

Authors

  • Şendağ YASLIKAYA Çukurova University Medical Oncology Department https://orcid.org/0000-0001-5264-8405
  • Mehmet TÜRKER Adana city training and research hospita
  • Yasemin AYDINALP CAMADAN "CUKUROVA UNIVERSITY MEDİCİNE FACULTY MEDICAL ONCOLOGY DEPARTMENT https://orcid.org/0000-0003-2435-368X
  • Mehmet Mutlu KIDI "CUKUROVA UNIVERSITY MEDİCİNE FACULTY MEDICAL ONCOLOGY DEPARTMENT
  • Sedat BİTER CUKUROVA UNIVERSITY MEDİCİNE FACULTY MEDICAL ONCOLOGY DEPARTMENT https://orcid.org/0000-0002-1053-0668
  • Esra ASARKAYA "CUKUROVA UNIVERSITY MEDİCİNE FACULTY MEDICAL ONCOLOGY DEPARTMENT
  • Hatice ASOĞLU RÜZGAR "CUKUROVA UNIVERSITY MEDİCİNE FACULTY MEDICAL ONCOLOGY DEPARTMENT https://orcid.org/0009-0000-1366-5552
  • Şüheda ATAŞ İPEK "CUKUROVA UNIVERSITY MEDİCİNE FACULTY MEDICAL ONCOLOGY DEPARTMENT
  • İ.Oğuz KARA "CUKUROVA UNIVERSITY MEDİCİNE FACULTY MEDICAL ONCOLOGY DEPARTMENT
  • Berksoy ŞAHİN "CUKUROVA UNIVERSITY MEDİCİNE FACULTY MEDICAL ONCOLOGY DEPARTMENT

DOI:

https://doi.org/10.37609/srinmed.20

Keywords:

colorectal cancer, circulating DNA, tumor markers

Abstract

Objective: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. ctDNA has emerged as a promising biomarker for CRC management, offering real-time insights into tumor burden and genetic mutations. This study investigates the correlation between CEA levels, ctDNA, clinicopathological factors, and treatment outcomes in early and advanced CRC patients.

Methods: The study retrospectively analyzed data from CRC patients, including  early-stage disease and metastatic disease. ctDNA levels, demographic data, and clinical parameters such as CEA, inflammatory indexes, and tumor characteristics were evaluated to determine correlations with treatment outcomes.

Results: The study included 20 patients, with 60% diagnosed at the metastatic stage.  The study found no statistically significant correlation between ctDNA levels and disease stage, recurrence, or overall survival. While CEA and ctDNA levels were measured, they did not demonstrate a significant relationship with treatment outcomes. Notably, ctDNA levels were higher in metastatic patients, though this was not statistically significant.

Conclusion: Despite its potential, the integration of ctDNA as a routine biomarker in CRC care faces challenges, including variability in measurement techniques and cost-effectiveness. However, ctDNA's ability to guide personalized treatment strategies and monitor disease recurrence holds promise. The study's findings align with previous research, suggesting ctDNA as a poor prognostic indicator, though further research is needed. ctDNA represents a significant advance in CRC management, offering non-invasive, real-time insights into tumor dynamics. Ongoing research is expected to solidify its role in personalized treatment planning, potentially leading to more effective and tailored therapies for CRC patients.

References

Fleischhacker M, Schmidt B. Circulating nucleic acids (CNAs) and cancer--a survey. Biochim Biophys Acta. 2007 Jan;1775(1):181-232. doi: 10.1016/j.bbcan.2006.10.001.

Merker JD, Oxnard GR, Compton C, Diehn M, Hurley P, Lazar AJ, Lindeman N, Lockwood CM, Rai AJ, Schilsky RL, Tsimberidou AM, Vasalos P, Billman BL, Oliver TK, Bruinooge SS, Hayes DF, Turner NC. Circulating Tumor DNA Analysis in Patients With Cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. J Clin Oncol. 2018 Jun 1;36(16):1631-1641. doi: 10.1200/JCO.2017.76.8671.

Haber DA, Velculescu VE. Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA. Cancer Discov. 2014 Jun;4(6):650-61. doi: 10.1158/2159-8290.CD-13-1014.

Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, Kinzler KW, Vogelstein B, Diaz LA Jr. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008 Sep;14(9):985-90. doi: 10.1038/nm.1789.

De Mattos-Arruda L, Mayor R, Ng CKY, Weigelt B, Martínez-Ricarte F, Torrejon D, Oliveira M, Arias A, Raventos C, Tang J, Guerini-Rocco E, Martínez-Sáez E, Lois S, Marín O, de la Cruz X, Piscuoglio S, Towers R, Vivancos A, Peg V, Ramon y Cajal S, Carles J, Rodon J, González-Cao M, Tabernero J, Felip E, Sahuquillo J, Berger MF, Cortes J, Reis-Filho JS, Seoane J. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nat Commun. 2015 Nov 10;6:8839. doi: 10.1038/ncomms9839.

Kimura H, Fujiwara Y, Sone T, Kunitoh H, Tamura T, Kasahara K, Nishio K. EGFR mutation status in tumour-derived DNA from pleural effusion fluid is a practical basis for predicting the response to gefitinib. Br J Cancer. 2006 Nov 20;95(10):1390-5. doi: 10.1038/sj.bjc.6603428.

Wang Y, Springer S, Mulvey CL, Silliman N, Schaefer J, Sausen M, James N, Rettig EM, Guo T, Pickering CR, Bishop JA, Chung CH, Califano JA, Eisele DW, Fakhry C, Gourin CG, Ha PK, Kang H, Kiess A, Koch WM, Myers JN, Quon H, Richmon JD, Sidransky D, Tufano RP, Westra WH, Bettegowda C, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Agrawal N. Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Sci Transl Med. 2015 Jun 24;7(293):293ra104. doi: 10.1126/scitranslmed.aaa8507.

Reckamp KL, Melnikova VO, Karlovich C, Sequist LV, Camidge DR, Wakelee H, Perol M, Oxnard GR, Kosco K, Croucher P, Samuelsz E, Vibat CR, Guerrero S, Geis J, Berz D, Mann E, Matheny S, Rolfe L, Raponi M, Erlander MG, Gadgeel S. A Highly Sensitive and Quantitative Test Platform for Detection of NSCLC EGFR Mutations in Urine and Plasma. J Thorac Oncol. 2016 Oct;11(10):1690-700. doi: 10.1016/j.jtho.2016.05.035

Siravegna G, Marsoni S, Siena S, Bardelli A. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol. 2017 Sep;14(9):531-548. doi: 10.1038/nrclinonc.2017.14.

Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih lM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014 Feb 19;6(224):224ra24. doi: 10.1126/scitranslmed.3007094.

Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.

Tie J, Cohen JD, Wang Y, Christie M, Simons K, Lee M, Wong R, Kosmider S, Ananda S, McKendrick J, Lee B, Cho JH, Faragher I, Jones IT, Ptak J, Schaeffer MJ, Silliman N, Dobbyn L, Li L, Tomasetti C, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer. JAMA Oncol. 2019 Dec 1;5(12):1710-1717. doi: 10.1001/jamaoncol.2019.3616. Erratum in: JAMA Oncol. 2019 Dec 1;5(12):1811. doi: 10.1001/jamaoncol.2019.5667.

Dasari A, Morris VK, Allegra CJ, Atreya C, Benson AB 3rd, Boland P, Chung K, Copur MS, Corcoran RB, Deming DA, Dwyer A, Diehn M, Eng C, George TJ, Gollub MJ, Goodwin RA, Hamilton SR, Hechtman JF, Hochster H, Hong TS, Innocenti F, Iqbal A, Jacobs SA, Kennecke HF, Lee JJ, Lieu CH, Lenz HJ, Lindwasser OW, Montagut C, Odisio B, Ou FS, Porter L, Raghav K, Schrag D, Scott AJ, Shi Q, Strickler JH, Venook A, Yaeger R, Yothers G, You YN, Zell JA, Kopetz S. ctDNA applications and integration in colorectal cancer: an NCI Colon and Rectal-Anal Task Forces whitepaper. Nat Rev Clin Oncol. 2020 Dec;17(12):757-770. doi: 10.1038/s41571-020-0392-0.

Henriksen TV, Tarazona N, Frydendahl A, Reinert T, Gimeno-Valiente F, Carbonell-Asins JA, Sharma S, Renner D, Hafez D, Roda D, Huerta M, Roselló S, Madsen AH, Løve US, Andersen PV, Thorlacius-Ussing O, Iversen LH, Gotschalck KA, Sethi H, Aleshin A, Cervantes A, Andersen CL. Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences. Clin Cancer Res. 2022 Feb 1;28(3):507-517. doi: 10.1158/1078-0432.CCR-21-2404.

Parikh AR, Van Seventer EE, Siravegna G, Hartwig AV, Jaimovich A, He Y, Kanter K, Fish MG, Fosbenner KD, Miao B, Phillips S, Carmichael JH, Sharma N, Jarnagin J, Baiev I, Shah YS, Fetter IJ, Shahzade HA, Allen JN, Blaszkowsky LS, Clark JW, Dubois JS, Franses JW, Giantonio BJ, Goyal L, Klempner SJ, Nipp RD, Roeland EJ, Ryan DP, Weekes CD, Wo JY, Hong TS, Bordeianou L, Ferrone CR, Qadan M, Kunitake H, Berger D, Ricciardi R, Cusack JC, Raymond VM, Talasaz A, Boland GM, Corcoran RB. Minimal Residual Disease Detection using a Plasma-only Circulating Tumor DNA Assay in Patients with Colorectal Cancer. Clin Cancer Res. 2021 Oct 15;27(20):5586-5594. doi: 10.1158/1078-0432.CCR-21-0410.

Kotaka M, Shirasu H, Watanabe J, Yamazaki K, Hirata K, Akazawa N, Matsuhashi N, Yokota M, Ikeda M, Kato K, Aleshin A, Sharma S, Kotani D, Oki E, Takemasa I, Kato T, Nakamura Y, Taniguchi H, Mori M, Yoshino T. Association of circulating tumor DNA dynamics with clinical outcomes in the adjuvant setting for patients with colorectal cancer from an observational GALAXY study in CIRCULATE-Japan. J Clin Oncol 2022; 40: 9.

Tsukada Y, Matsuhashi N, Murano T, et al. Impact of postoperative integrated genomic and epigenomic signatures of circulating tumor DNA (ctDNA) on recurrence in resected colorectal cancer: initial report of a prospective ctDNA monitoring study COSMOS-CRC-01. J Clin Oncol 2022; 40: 168. DOI: 10.1200/JCO.2022.40.4_suppl.168

Wang Y, Li L, Cohen JD, Kinde I, Ptak J, Popoli M, Schaefer J, Silliman N, Dobbyn L, Tie J, Gibbs P, Tomasetti C, Kinzler KW, Papadopoulos N, Vogelstein B, Olsson L. Prognostic Potential of Circulating Tumor DNA Measurement in Postoperative Surveillance of Nonmetastatic Colorectal Cancer. JAMA Oncol. 2019 Aug 1;5(8):1118-1123. doi: 10.1001/jamaoncol.2019.0512.

Henriksen TV, Tarazona N, Reinert T, Carbonell-Asins JA, Renner D, Sharma S et al. Circulating tumor DNA analysis for assessment of recurrence risk, benefit of adjuvant therapy, and early relapse detection after treatment in colorectal cancer patients. Journal of Clinical Oncology. 2021;39(3 Suppl. ):11. doi: 10.1200/JCO.2021.39.3_suppl.11

Bando H, Nakamura Y, Taniguchi H, Shiozawa M, Yasui H, Esaki T, Kagawa Y, Denda T, Satoh T, Yamazaki K, Sunakawa Y, Kato T, Goto M, Yuki S, Nishina T, Oki E, Shinozaki E, Matsuhashi N, Takahashi N, Tsuji A, Ohtsubo K, Wakabayashi M, Ikeno T, Hata M, Odegaard JI, Yoshino T. Effects of Metastatic Sites on Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer. JCO Precis Oncol. 2022 Apr;6:e2100535. doi: 10.1200/PO.21.00535.

Xue J, Prabhakaran S, Prabhakaran S, Lim WM, Guerra G, Heriot A, Kong JC. The utility of ctDNA in colorectal cancer with peritoneal metastases. ANZ J Surg. 2023 Mar;93(3):506-509. doi: 10.1111/ans.18078.

Lee S, Park YS, Chang WJ, Choi JY, Lim A, Kim B, Lee SB, Lee JW, Kim SH, Kim J, Kwak JM, Yoon KC, Lee SH, Kim YH. Clinical Implication of Liquid Biopsy in Colorectal Cancer Patients Treated with Metastasectomy. Cancers (Basel). 2021 May 6;13(9):2231. doi: 10.3390/cancers13092231.

Tie J, Cohen JD, Wang Y, Christie M, Simons K, Lee M, Wong R, Kosmider S, Ananda S, McKendrick J, Lee B, Cho JH, Faragher I, Jones IT, Ptak J, Schaeffer MJ, Silliman N, Dobbyn L, Li L, Tomasetti C, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer. JAMA Oncol. 2019 Dec 1;5(12):1710-1717. doi: 10.1001/jamaoncol.2019.3616. Erratum in: JAMA Oncol. 2019 Dec 1;5(12):1811. doi: 10.1001/jamaoncol.2019.5667.

Fakih M, Sandhu J, Wang C, Kim J, Chen YJ, Lai L, Melstrom K, Kaiser A. Evaluation of Comparative Surveillance Strategies of Circulating Tumor DNA, Imaging, and Carcinoembryonic Antigen Levels in Patients With Resected Colorectal Cancer. JAMA Netw Open. 2022 Mar 1;5(3):e221093. doi: 10.1001/jamanetworkopen.2022.1093

Soueidy C,Zaanan A,Gelli M, et al. Clinical impact of circulating tumor DNA to track minimal residual disease in colorectal cancer patients. Hopes and limitations. ESMO gastroint. Oncol. 2024; 4:100068. DOI:https://doi.org/10.1016/j.esmogo.2024.100068

Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, Wong R, Shapiro J, Lee M, Harris S, Khattak A, Burge M, Harris M, Lynam J, Nott L, Day F, Hayes T, McLachlan SA, Lee B, Ptak J, Silliman N, Dobbyn L, Popoli M, Hruban R, Lennon AM, Papadopoulos N, Kinzler KW, Vogelstein B, Tomasetti C, Gibbs P; DYNAMIC Investigators. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. N Engl J Med. 2022 Jun 16;386(24):2261-2272. doi: 10.1056/NEJMoa2200075.

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Published

2024-10-24

How to Cite

YASLIKAYA, Şendağ, TÜRKER, M., AYDINALP CAMADAN, Y., KIDI, M. M., BİTER, S., ASARKAYA, E., … ŞAHİN, B. (2024). The Evaluation of Circulating Tumor DNA and Carcinoembryonic Antigen Levels and Relationship with Clinicopathological Risk Factors and Prognostic Indices in Colorectal Cancer Patients: ctDNA and CEA Relationship in Colorectal Cancer. Scientific Reports in Medicine, 1(2). https://doi.org/10.37609/srinmed.20

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Research Articles