Year 2023 Vol. 31 No 4

SCIENTIFIC PUBLICATIONS

A.V. OREKHVA 1, 2, E.A. SHLIAKHTUNOV 2, I.V. ZHILTSOV 2, V.M. SEMENOV 2, E.V. KARCHMIT 1, G.M. SHAPPO 2, , J.N. LYACH 1, A.V. OREKHVA 3

MONITORING OF MINIMAL RESIDUAL DISEASE IN COLORECTAL CANCER BASED ON THE ASSESSMENT OF SURVIVIN (BIRC5) MRNA EXPRESSION IN CIRCULATING TUMOR CELLS

Health Institution "Vitebsk Regional Clinical Oncology Dispensary" 1,
Educational Establishment "Vitebsk State Medical University" 2,
Health Institution "Vitebsk Regional Clinical Diagnostic Center 3, Vitebsk,
Republic of Belarus

Objective. To assess the clinical significance of survivin (BIRC5) mRNA expression in circulating tumor cells (CTCs) in colorectal cancer (CRC).
Methods. The study involved 130 patients (109 patients with colorectal cancer and 21 patients with colon adenomas). All patients underwent complete tumor resection (radical surgery 102 (93.6%), cytoreductive 7 (6.4%)). Monitoring of survivin mRNA (BIRC5) expression in the CTC was performed within 9 months after surgery. The expression study was performed using RT-PCR, the normalized expression of the BIRC5 gene in the CTCs was examined.
Results. A high level of survivin (BIRC5) mRNA expression was found in CTCs in CRC compared to adenomas (p<0.001), both prior surgery MSD (1.1751.33 and 0.0520.11) and after 3 months MSD (1.0150.93 and 0.0180.002). A relationship was found between the presence of CTCs in patients prior surgery and damage of regional lymph nodes (p=0.032), stage of the tumor process (p=0.011), tumor size (p=0.038), degree of tumor differentiation (p=0.039), positive expression of survivin mRNA ( BIRC5) in tumor material (p=0.044) . In 6 and 9 months after surgery, CTCs persist in the bloodstream, even despite adjuvant chemotherapy in patients with stage III disease (p=0.015 and p=0.012).
Conclusion. Survivin is a highly sensitive tumor marker in CRC due to its overexpression in the CTC. Overexpression of survivin mRNA in CRC has been identified as negative prognostic factor and directly depends on the tumor lesion of the regional lymph nodes, the stage of the disease, the degree of tumor differentiation, and the size of the tumor. In 9 months after radical surgery determination of survivin (BIRC5) mRNA expression in the CTC can be used for assessment of minimal residual disease and considered as a powerful prognostic factor of the overall survival rate.

Keywords: BIRC5, survivin, minimal residual disease, circulating tumor cells, colorectal cancer
p. 322-331 of the original issue
References
  1. 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
  2. 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
  3. Tarazona N, Gimeno-Valiente F, Gambardella V, Zuñiga S, Rentero-Garrido P, Huerta M, Roselló S, Martinez-Ciarpaglini C, Carbonell-Asins JA, Carrasco F, Ferrer-Martínez A, Bruixola G, Fleitas T, Martín J, Tébar-Martínez R, Moro D, Castillo J, Espí A, Roda D, Cervantes A. Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer. Ann Oncol. 2019 Nov 1;30(11):1804-12. doi: 10.1093/annonc/mdz390
  4. Rahbari NN, Aigner M, Thorlund K, Mollberg N, Motschall E, Jensen K, Diener MK, Büchler MW, Koch M, Weitz J. Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology. 2010 May;138(5):1714-26. doi: 10.1053/j.gastro.2010.01.008
  5. Yang C, Zou K, Zheng L, Xiong B. Prognostic and clinicopathological significance of circulating tumor cells detected by RT-PCR in non-metastatic colorectal cancer: a meta-analysis and systematic review. BMC Cancer. 2017 Nov 7;17(1):725. doi: 10.1186/s12885-017-3704-8
  6. Alberter B, Klein CA, Polzer B. Single-cell analysis of CTCs with diagnostic precision: opportunities and challenges for personalized medicine. Expert Rev Mol Diagn. 2016;16(1):25-38. doi: 10.1586/14737159.2016.1121099
  7. Alberter B, Klein CA, Polzer B. Single-cell analysis of CTCs with diagnostic precision: opportunities and challenges for personalized medicine. Expert Rev Mol Diagn. 2016;16(1):25-38. doi: 10.1586/14737159.2016.1121099
  8. de Gramont A, Tournigand C, André T, Larsen AK, Louvet C. Targeted agents for adjuvant therapy of colon cancer. Semin Oncol. 2006 Dec;33(6 Suppl 11):S42-5. doi: 10.1053/j.seminoncol.2006.10.006
  9. de Almagro MC, Vucic D. The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy. Exp Oncol. 2012 Oct;34(3):200-11.
  10. Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T, Altieri DC. IAP regulation of metastasis. Cancer Cell. 2010 Jan 19;17(1):53-64. doi: 10.1016/j.ccr.2009.11.021
  11. Zhang T, Fields JZ, Opdenaker L, Otevrel T, Masuda E, Palazzo JP, Isenberg GA, Goldstein SD, Brand M, Boman BM. Survivin-induced Aurora-B kinase activation: A mechanism by which APC mutations contribute to increased mitoses during colon cancer development. Am J Pathol. 2010 Dec;177(6):2816-26. doi: 10.2353/ajpath.2010.100047
  12. Jakubowska K, Pryczynicz A, Dymicka-Piekarska V, Famulski W, Guzińska-Ustymowicz K. Immunohistochemical expression and serum level of survivin protein in colorectal cancer patients. Oncol Lett. 2016 Nov;12(5):3591-97. doi: 10.3892/ol.2016.5075
  13. Krieg A, Werner TA, Verde PE, Stoecklein NH, Knoefel WT. Prognostic and clinicopathological significance of survivin in colorectal cancer: a meta-analysis. PLoS One. 2013 Jun 3;8(6):e65338. doi: 10.1371/journal.pone.0065338. Print 2013.
  14. Huang YJ, Qi WX, He AN, Sun YJ, Shen Z, Yao Y. The prognostic value of survivin expression in patients with colorectal carcinoma: a meta-analysis. Jpn J Clin Oncol. 2013 Oct;43(10):988-95. doi: 10.1093/jjco/hyt103
Address for correspondence:
210009, Republic of Belarus,
Vitebsk, Frunze Ave., 27,
Vitebsk State Medical Univercity.
tel.: +375-33-900-44-00,
e-mail: dr.orehva@yandex.ru,
Orekhva Andrey V.
Information about the authors:
Orekhva Andrey V., Oncologist-Surgeon of the Oncological Abdominal Department of Vitebsk Regional Clinical Oncological Dispensary, Applicant for the Department of Oncology with Courses of LD, LT, FPC and PC. Vitebsk State Medical University, Vitebsk, Republic of Belarus.
https://orcid.org/0000-0001-9145-4216
Shlyakhtunov Evgenij A., MD, Associate Professor, Head of the Department of Oncology with Courses of LD, LT, FPC and PC Vitebsk State Medical University, Vitebsk, Republic of Belarus.
https://orcid.org/0000-0002-5906-5373
Semenov Valery M., MD, Professor, Head of the Department of Infectious Diseases, Vitebsk State Medical University, Vitebsk, Republic of Belarus.
https://orcid.org/0000-0002-7029-9226
Zhiltsov Ivan V., MD, Professor, Head of the Department of Evidence-Based Medicine and Clinical Diagnostics FPC and PC, Vitebsk State Medical University, Vitebsk, Republic of Belarus.
https://orcid.org/0000-0002-4912-2880
Shappo Galina M., PhD, Associate Professor of the Department of Oncology with Courses of LD, LT, FPC and PC Vitebsk State Medical University, Vitebsk, Republic of Belarus.
https://orcid.org/0000-0002-2147-3937
Lyakh Yan N., Oncologist of the Oncological Polyclinic Department of the Vitebsk Regional Clinical Oncological Dispensary, Vitebsk, Republic of Belarus.
https://orcid.org/0009-0001-2385-4880
Karchmit Evgenia V., Head of the Oncological Polyclinic Department of Vitebsk Regional Clinical Oncological Dispensary, Vitebsk, Republic of Belarus.
https://orcid.org/0009-0009-0231-7945
Orekhva Alina V., Radiologist of the Department of Radiation Diagnostics of Vitebsk Regional Clinical Diagnostic Center, Vitebsk, Republic of Belarus.
https://orcid.org/0009-0007-4484-6736
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