Comparative analysis of the diagnostic accuracy of endostatin and vegf serum levels in patients with bone sarcomas

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Introduction. Angiogenesis regulators are of particular interest as new serum markers in cancer patients, since they reflect the intensity of tumor growth and metastasis. Currently, many works are dedicated to the study of vascular endothelial growth factor (VEGF), which activates angiogenesis, and endostatin, which inhibits it. However, a comparative study of the diagnostic accuracy of serum levels of these two markers in patients with bone sarcomas has not been conducted yet.

Аim. A comparative analysis of the diagnostic accuracy indicators and prognostic significance of VEGF and endostatin in the blood serum of patients with primary malignant bone tumors.

Methods. During the study, the levels of endostatin and VEGF in blood serum samples from 123 patients with a newly diagnosed and morphologically verified bone sarcoma were measured. Patients were examined at the Federal State Budgetary Institution “National Medical Research Center of Oncology named after N.N. Blokhin” of the Russian Ministry of Health from July 2001 to December 2022. Sixty age- and gender-matched healthy donors were included in the control group.

Results. Median serum concentrations of endostatin and VEGF in the patient group were statistically significantly increased compared to the control group by 1.3 and 1.4 times, respectively (p<0.01). Statistically significant differences in the serum concentrations of VEGF and endostatin depending on the T category and the tumor grade and stage were not identified. The cut-off value of VEGF was 279 pg/ml, and the cut-off value of endostatin was 121 ng/ml. With the same sensitivity of 75.6%, endostatin is characterized by higher specificity than VEGF (73.0 and 67.6%, respectively). The proportional hazards model characterizing the effect of serum VEGF and endostatin levels on overall and survival was not statistically significant.

Conclusion. Endostatin in the blood serum of patients with bone tumors is more informative compared to VEGF; however, both markers are not predictors of overall and survival.

Full Text

Restricted Access

About the authors

Olga Nikolaevna Merkureva

Institution «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation; FSBEI HE “ROSUNIMED” of MOH of Russia

Author for correspondence.
Email: merkureva.o.n@gmail.com
ORCID iD: 0000-0001-6744-005X

Specialist in Laboratory Medicine, FSBI «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation. Рostgraduate Student, FSBEI HE “ROSUNIMED” of MOH of Russia

Russian Federation, Kashirskoye shosse, 24, Moscow, 115522; Dolgorukovskaya ul., 4, Moscow, 127006

Igor Nikolaevich Kuznetsov

FSBEI HE “ROSUNIMED” of MOH of Russia

Email: npkredo@yandex.ru
ORCID iD: 0000-0003-0866-5501

Candidate of biological sciences. Research assistant, Department of Clinical Biochemistry and Laboratory Diagnostics

Russian Federation, Dolgorukovskaya ul., 4, Moscow, 127006

Irina Valentinovna Babkina

Institution «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation; FSBEI HE “ROSUNIMED” of MOH of Russia

Email: docbabkina@rambler.ru
ORCID iD: 0000-0001-9285-3470

Doctor of medical sciences. Specialist in Laboratory Medicine, FSBI «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation. Professor, Department of Clinical Biochemistry and Laboratory Diagnostics, FSBEI HE “ROSUNIMED” of MOH of Russia

Russian Federation, Kashirskoye shosse, 24, Moscow, 115522; Dolgorukovskaya ul., 4, Moscow, 127006

Dmitriy Viktorovich Rogozhin

Institution «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation

Email: pathol.777@mail.ru
ORCID iD: 0000-0003-0777-9152

Doctor of medical sciences. Head of the Pathology Department

Russian Federation, Kashirskoye shosse, 24, Moscow, 115522

Evgeniy Alexandrovich Sushentsov

Institution «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation

Email: crcspine@rambler.ru
ORCID iD: 0000-0003-3672-1742

Candidate of medical sciences. Head of the Department of bone and soft tissue tumors №2 (Onco-Orthopedics)

Russian Federation, Kashirskoye shosse, 24, Moscow, 115522

Elena Sergeevna Gershtein

Institution «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation; FSBEI HE “ROSUNIMED” of MOH of Russia

Email: esgershtein@gmail.com
ORCID iD: 0000-0002-3321-801X

Doctor of biological sciences, Professor. Leading scientific worker, FSBI «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation. Professor, Department of Clinical Biochemistry and Laboratory Diagnostics, FSBEI HE “ROSUNIMED” of MOH of Russia

Russian Federation, Kashirskoye shosse, 24, Moscow, 115522; Dolgorukovskaya ul., 4, Moscow, 127006

Nikolay Evgenevich Kushlinskii

Institution «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation; FSBEI HE “ROSUNIMED” of MOH of Russia

Email: biochimia@yandex.ru
ORCID iD: 0000-0002-3898-4127

Doctor of medical sciences, Professor, Academician of the Russian Academy of Sciences. Scientific Director of the Clinical Diagnostic Laboratory, FSBI «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation. Head of the Department of Clinical Biochemistry and Laboratory Diagnostics, FSBEI HE “ROSUNIMED” of MOH of Russia

Russian Federation, Kashirskoye shosse, 24, Moscow, 115522; Dolgorukovskaya ul., 4, Moscow, 127006

References

  1. Choi J.H., Ro J.Y. The 2020 WHO Classification of Tumors of Bone: An Updated Review. Adv. Anat. Pathol. 2021; 28 (3): 119–38.
  2. Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022; 12 (1): 31–46. doi: 10.1158/2159-8290.CD-21-1059
  3. Goel S., Duda D. G., Xu L. Munn L.L., Boucher Y., Fukumura D., Jain R.K. Normalization of the vasculature for treatment of cancer and other diseases. Physiol. Rev. 2011; 91 (3): 1071–121. doi: 10.1152/physrev.00038.2010.
  4. Shinkaruk S., Bayle M., Laïn G., Déléris G. Vascular endothelial cell growth factor (VEGF), an emerging target for cancer chemotherapy. Curr. Med. Chem. Anticancer Agents. 2003; 3 (2): 95–117. doi: 10.2174/1568011033353452
  5. Goggins E., Mironchik Y., Kakkad S., Jacob D., Wildes F., Bhujwalla Z.M., Krishnamachary B. Reprogramming of VEGF-mediated extracellular matrix changes through autocrine signaling. Cancer Biol. Ther. 2023; 24 (1): 2184145. doi: 10.1080/15384047.2023.2184145
  6. Dixelius J., Cross M., Matsumoto T., Sasaki T., Timpl R., Claesson-Welsh L. Endostatin regulates endothelial cell adhesion and cytoskeletal organization. Cancer Res. 2002; 62 (7): 1944–7. PMID: 11929807
  7. Dhanabal M., Ramchandran R., Waterman M.J., Lu H., Knebelmann B., Segal M., Sukhatme V.P. Endostatin induces endothelial cell apoptosis. J. Biol. Chem. 1999; 274 (17): 11721–6. doi: 10.1074/jbc.274.17.11721
  8. Hanai J., Dhanabal M., Karumanchi S.A., Albanese C., Waterman M., Chan B., Ramchandran R., Pestell R., Sukhatme V.P. Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1. J. Biol. Chem. 2002; 277 (19): 16464–9. doi: 10.1074/jbc.M112274200
  9. Kantola T., Väyrynen J.P., Klintrup K., Mäkelä J., Karppinen S.M., Pihlajaniemi T., Autio-Harmainen H., Karttunen T.J., Mäkinen M.J., Tuomisto A. Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers. Br. J. Cancer. 2014; 111 (8): 1605–13. doi: 10.1038/bjc.2014.456
  10. Mardani M., Andishe Tadbir A., Ranjbar M.A., Khademi B., Fattahi M.J., Rahbar A. Serum endostatin levels in oral squamous cell carcinoma. Iranian J. Otorhinolaryngol. 2018; 30 (98): 125–30. PMID: 29876326
  11. Frezzetti D., Gallo M., Maiello M.R., D’Alessio A., Esposito C., Chicchinelli N., Normanno N., De Luca A. VEGF as a potential target in lung cancer. Expert Opin. Ther. Targets. 2017; 21 (10): 959–66. doi: 10.1080/14728222.2017.1371137
  12. Меркурьева О.Н., Кушлинский Н.Е. Эндостатин – биомаркер ангиогенеза у больных опухолями костей: систематический обзор и метаанализ. Технологии живых систем. 2023; 20 (3): 6–16. doi: 10.18127/j20700997-202303-02. [Merkurieva O.N., Kushlinskii N.E. Endostatin as a biomarker of angiogenesis in patients with bone sarcomas: a systematic review and meta-analysis. Tekhnologii zhivykh sistems. 2023; 20 (3): 6-16. doi: 10.18127/j20700997-202303-02 (In Russian)].
  13. Chen Z., Chen Q.X., Hou Z.Y., Hu J., Cao Y.G. Clinical predictive value of serum angiogenic factor in patients with osteosarcoma. Asian Pac. J. Cancer Prev. 2012; 13 (9): 4823–6. doi: 10.7314/apjcp.2012.13.9.4823
  14. Urunbaev S., Abdikarimov K.G., Polatova D.S. Serum Factors of Angiogenesis and the Growth of Fibroblasts in Osteogenic Sarcoma. Ann. Oncol. 2014; 25 (4): 509. doi: 10.1093/annonc/mdu354.48
  15. Меркурьева О.Н., Бабкина И.В., Булычева И.В. Прищеп П.Л., Романцева О.М., Варфоломеева С.Р., Кушлинский Н.Е. Клинико-лабораторное значение эндостатина в сыворотке крови подростков с саркомами костей. Технологии живых систем. 2022; 19 (4): 24–32. doi: 10.18127/j20700997-202204-02. [Merkuryeva O.N., Babkina I.V., Bulycheva I.V., Prishchep P.L., Romantsova O.M., Varfolomeeva S.R., Kushlinskii N.E. Clinical and laboraory significance of endostatin in the blood serum of adolescents with bone sarcomas. Tekhnologii zhivykh sistems. 2022; 19 (4): 24-32. doi: 10.18127/j20700997-202204-02 (In Russian)].
  16. DuBois S., Demetri G. Markers of angiogenesis and clinical features in patients with sarcoma. Cancer. 2007; 109 (5): 813–9. doi: 10.1002/cncr.22455
  17. Бабкина И.В. Алферов А.А., Бондарев А.В., Щупак М.Ю., Кузнецов И.Н., Булычева И.В., Соловьев Ю.Н., Алиев М.Д., Кушлинский Н.Е. Клинический анализ сывороточных уровней интерлейкина-16 и фактора роста эндотелия сосудов с учетом морфологических характеристик новообразований и отдаленных результатов лечения больных опухолями костей. Альманах Клин. Мед. 2016; 44 (5): 606–12. doi: 10.18786/2072-0505-2016-44-5-606-612. [Babkina I.V., Alferov A.A., Bondarev A.V., Shchupa M.Y., Kuznetsov I.N., Boulytcheva I.V., Solovev Yu.N., Aliev M.D., Kushlinskii N.E. Clinical analysis of serum interleukin-16 and vascular endothelial growth factor levels depending on morphological characteristics of the tumors and long-term treatment outcomes in patients with bone neoplasms. Almanac of Clinical Medicine. 2016; 44 (5): 606–12. doi: 10.18786/2072-0505-2016-44-5-606-612 (In Russian)
  18. Dou B., Chen T., Chu Q., Zhang G., Meng Z. The roles of metastasis-related proteins in the development of giant cell tumor of bone, osteosarcoma and Ewing’s sarcoma. Technol. Health Care. 2021; 29 (S1): 91–101. doi: 10.3233/THC-218010

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Serum endostatin levels in the patients with bone sarcomas and the healthy donors

Download (166KB)
Indexing metadata
3. Fig. 2. Serum VEGF levels in the patients with bone sarcomas and the healthy donors

Download (166KB)
Indexing metadata
4. Fig. 3. The correlation between serum VEGF level and primary bone sarcomas

Download (224KB)
Indexing metadata
5. Fig. 4. The correlation between serum endostatin level and primary bone sarcomas

Download (239KB)
Indexing metadata
6. Fig. 5. Kaplan–Meier survival curve for overall survival of patients with bone sarcomas

Download (250KB)
Indexing metadata

Copyright (c) 2024 Russkiy Vrach Publishing House