LONG-TERM TREATMENT RESULTS OF BONE SARCOMA PATIENTS WITH CONSIDERATION OF SERUM METALLOPROTEINASE LEVELS

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Abstract

Background: Bone sarcomas are extremely malignant prone to rapid hematogenic metastasing. Evaluation of biological marker expression by the tumor is important not only for the search of new potential chemotherapy targets, but for the assessment of the disease prognosis.
Aim: A comparative evaluation of matrix metalloproteinases (MMP)-2, -7, -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the serum of patients with primary bone tumors and in healthy people to identify their potential association with the histological characteristics of the tumor and the disease prognosis.
Materials and methods: A comparative study of serum MMP-2, -7, -9, and TIMP-1 levels was performed in 54 patients with primary bone tumors (malignant, 45 patients, including central osteosarcoma in 21, periosteal osteosarcoma in 4, Ewing's sarcoma in 11, primary chondrosarcoma in 6, undifferentiated pleomorphic sarcoma in 3, and borderline giant cell tumors in 9) and in 26 healthy individuals with the use of the immunoenzyme technique (Biosource, USA, for TIMP-1 and R&D, USA, for MMP-2, -7, and -9).
Results: The TIMP-1 levels in the serum of patients with central and periosteal osteosarcomas were significantly higher than in the serum of healthy controls (р = 0.038 and p = 0.007, respectively). The MMP-9 levels in patients with bone malignancies were significantly lower than that in the normal controls (p < 0.05). There was a positive correlation between serum TIMP-1 and MMP-9 levels in patients with central, periosteal and Ewing's sarcomas (r = 0.37, p = 0.024). No significant differences in the 5-year survival rates related to serum TIMP-1, MMP-2, -7, -9 levels were found in patients with bone sarcomas. However, in those with osteosarcoma and serum MMP-2 > 160 ng/ml, the overall 5-year survival rate was 1.6-fold higher than in those with lower MMP-2 levels, and in those with ММP-9 levels < 377 ng/ml, the 5-year survival rate was 1.4-fold higher than in patients with ММP- 9 > 377 ng/ml. The worst 5-year survival (33%) was found in the patients with serum ММP-2 levels of less than 160 ng/ml and ММP-9 of more than 377 ng/ml. Conclusion: The results obtain suggest that the expression of MMP-2, MMP-9 and TIMP-1 could be associated with pathophysiological changes related to growth and metastatic process of bone sarcomas and osteosarcoma, in particular. This area could be an object for further studies on levels of these biomarkers and their prognostic value in bone malignancies.

About the authors

I. V. Babkina

N.N. Blokhin Russian Cancer Research Center, Moscow

Author for correspondence.
Email: docbabkina@rambler.ru
Babkina Irina Valentinovna – MD, PhD, Professor, Leading Research Fellow, Clinical Biochemistry Laboratory Russian Federation

A. V. Bondarev

Moscow Municipal Oncologic Hospital No. 62,Istra poselok, p/o Stepanovskoe, Krasnogorskiy rayon, Moskovskaya oblast'

Email: docbabkina@rambler.ru
Bondarev Aleksandr Viktorovich – Orthopaedic Surgeon, Orthopaedic Department Russian Federation

M. Yu Shchupak

Moscow Municipal Oncologic Hospital No. 62,Istra poselok, p/o Stepanovskoe, Krasnogorskiy rayon, Moskovskaya oblast'

Email: docbabkina@rambler.ru
Shchupak Mikhail Yur'evich – Orthopaedic Surgeon, Head of Orthopaedic Department Russian Federation

I. V. Boulytcheva

N.N. Blokhin Russian Cancer Research Center, Moscow

Email: docbabkina@rambler.ru
Boulytcheva Irina Vladislavovna – MD, PhD, Surgical Pathologist, Pathology Department Russian Federation

Yu. N. Soloviev

N.N. Blokhin Russian Cancer Research Center, Moscow

Email: docbabkina@rambler.ru
Soloviev Yuriy Nikolaevich – MD, PhD, Professor, Academician RAS, Chief  Research Fellow, Pathology Department Russian Federation

A. N. Makhson

Moscow Municipal Oncologic Hospital No. 62,Istra poselok, p/o Stepanovskoe, Krasnogorskiy rayon, Moskovskaya oblast'

Email: docbabkina@rambler.ru
Makhson Anatoliy Nakhimovich – MD, PhD, Professor, Chief Surgeon Russian Federation

M. D. Aliev

N.N. Blokhin Russian Cancer Research Center, Moscow

Email: docbabkina@rambler.ru
Aliev Mamed Dzhavadovich – MD, PhD, Professor, Academician RAS, Chief  of Department of General Oncology Russian Federation

N. E. Kushlinskii

N.N. Blokhin Russian Cancer Research Center, Moscow

Email: docbabkina@rambler.ru
Kushlinskii Nikolay Evgen'evich – MD, PhD, Professor, Member-Correspondent of Russian Academy of Sciences, Head of Clinical Biochemistry Laboratory Russian Federation

References

  1. Wu D, Chen K, Bai Y, Zhu X, Chen Z, Wang C, Zhao Y, Li M. Screening of diagnostic markers for osteosarcoma. Mol Med Rep. 2014;10(5):2415– 20. doi: 10.3892/mmr.2014.2546.
  2. Mohammed MA, Seleim MF, Abdalla MS, Sharada HM, Abdel Wahab AH. Urinary high molecular weight matrix metalloproteinases as non-invasive biomarker for detection of bladder cancer. BMC Urol. 2013;13:25. doi: 10.1186/1471-2490-13-25.
  3. Weng Y, Cai M, Zhu J, Geng J, Zhu K, Jin X, Ding W. Matrix metalloproteinase activity in early-stage lung cancer. Onkologie. 2013;36(5):256–9. doi: 10.1159/000350304.
  4. Kojima T, Wang X, Fujiwara K, Osaka S, Yoshida Y, Osaka E, Taniguchi M, Ueno T, Fukuda N, Soma M, Tokuhashi Y, Nagase H. Inhibition of human osteosarcoma cell migration and invasion by a gene silencer, pyrrole-imidazole polyamide, targeted at the human MMP9 NF-κB binding site. Biol Pharm Bull. 2014;37(9):1460–5.
  5. Han J, Yong B, Luo C, Tan P, Peng T, Shen J. High serum alkaline phosphatase cooperating with MMP-9 predicts metastasis and poor prognosis in patients with primary osteosarcoma in Southern China. World J Surg Oncol. 2012;10:37. doi: 10.1186/1477-7819-10-37.
  6. Li H, Zhang K, Liu LH, Ouyang Y, Bu J, Guo HB, Xiao T. A systematic review of matrix metalloproteinase 9 as a biomarker of survival in patients with osteosarcoma. Tumour Biol. 2014;35(6):5487–91. doi: 10.1007/s13277-0141717-3.
  7. Zhang Q, Li J, Liu F, Li Z. Comments on Li H et al. “A systematic review of matrix metalloproteinase 9 as a biomarker of survival in patients with osteosarcoma”. Tumour Biol. 2015;36(1):5–6. doi: 10.1007/s13277-014-2857-1.
  8. Korpi JT, Hagström J, Lehtonen N, Parkkinen J, Sorsa T, Salo T, Laitinen M. Expression of matrix metalloproteinases-2, -8, -13, -26, and tissue inhibitors of metalloproteinase-1 in human osteosarcoma. Surg Oncol. 2011;20(1):e18–22. doi: 10.1016/j.suronc.2010.08.004.
  9. Yang SF, Lee WJ, Tan P, Tang CH, Hsiao M, Hsieh FK, Chien MH. Upregulation of miR-328 and inhibition of CREB-DNA-binding activity are critical for resveratrol-mediated suppression of matrix metalloproteinase-2 and subsequent metastatic ability in human osteosarcomas. Oncotarget. 2015;6(5):2736–53.

Copyright (c) 2015 Babkina I.V., Bondarev A.V., Shchupak M.Y., Boulytcheva I.V., Soloviev Y.N., Makhson A.N., Aliev M.D., Kushlinskii N.E.

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