Effects of Surgery Combined with Different Chemotherapy on Matrix Metalloproteinase-9 and Tissue Inhibitors of Metalloproteinase-1 in Children with Neuroblastoma

Overview

Journal J Oncol

Specialty Oncology

Date 2022 Jul 18

PMID 35847358

Authors

Zilong Qi

Xinning Wang

Liang Yin

Kun Ma

Lei Chen

Jinmin Li

Affiliations

Soon will be listed here.

Abstract

Background: Neuroblastoma (NB) is a common extracranial malignancy in children and accounts for 15% of all cancer-related deaths in children, with the 5-year survival of patients in an advanced stage being lower than 40%. Preoperative adjuvant chemotherapy has been reported to facilitate surgical resection and improve the 2-year survival of patients.

Objective: To analyze the efficacy of surgery plus different chemotherapy on children with NB and to investigate the correlation of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase-1 (TIMP-1) with chemotherapy efficacy.

Methods: From April 2005 to May 2017, a total of 92 cases of NB treated in our hospital were assessed for eligibility and recruited. They were assigned at a ratio of 1: 1 to receive either CAV (cyclophosphamide + vincristine + adriamycin) (group A) and EP (etoposide + cisplatin) alternately or TOPO (topotecan) + CTX (cytoxan) + CiE (etoposide + cisplatin) + CPV (cyclophosphamide + pirarubicin + vincristine) (group B). The outcome measures include chemotherapy efficacy, surgical resection rates, complications, 2-year recurrence, and 2-year survival. The levels of NK cells, CD4+/CD8+ cells, MMP-9, TIMP-1, and urine catecholamine (VMA) in peripheral blood of patients before and after initial chemotherapy were determined to analyze the correlation of MMP-9, TIMP-1, and VMA with the efficacy of chemotherapy.

Results: The two groups had similar efficacy (84.00% vs. 95.24%) and surgical resection rates (60.00% vs. 61.90%) after the initial chemotherapy ( > 0.05). Surgery for all eligible patients was successful after second chemotherapy. All eligible patients showed myelosuppression after chemotherapy, including 48 cases with stages I-II (52.17%) and 44 cases with stages III-IV (47.83%). The ratio of CD4+/CD8+ cells, MMP-9, TIMP-1, and VMA expression levels in peripheral blood of patients decreased ( < 0.05) after chemotherapy, and the ratio of CD4+/CD8+ cells was further reduced after surgery ( < 0.05), while natural killer (NK) cells levels increased ( < 0.05). However, intergroup differences were absent in the incidence of myelosuppression, CD4+/CD8+ cell ratio, NK cells, MMP-9, TIMP-1, and VMA expression levels ( > 0.05). MMP-9 and TIMP-1 were positively correlated with VMA ( < 0.05), and the expression levels of MMP-9 and TIMP-1 and VMA after chemotherapy were negatively correlated with chemotherapy efficiency ( < 0.05). Patients with high expressions of MMP-9, TIMP-1, and VMA were associated with lower 2-year survival versus those with low expressions ( < 0.05).

Conclusion: Surgery plus chemotherapy for children with NB yields a promising clinical efficacy and a favorable surgical resection outcome. MMP-9 and TIMP-1 may be the potential biological indicators for chemotherapy efficiency and have a reference value for following surgical treatment of patients.

References

Zingoni A, Fionda C, Borrelli C, Cippitelli M, Santoni A, Soriani A . Natural Killer Cell Response to Chemotherapy-Stressed Cancer Cells: Role in Tumor Immunosurveillance. Front Immunol. 2017; 8:1194. PMC: 5622151. DOI: 10.3389/fimmu.2017.01194. View

Kaneko M, Tsuchida Y, Mugishima H, Ohnuma N, Yamamoto K, Kawa K . Intensified chemotherapy increases the survival rates in patients with stage 4 neuroblastoma with MYCN amplification. J Pediatr Hematol Oncol. 2002; 24(8):613-21. DOI: 10.1097/00043426-200211000-00004. View

Cornen S, Vivier E . Chemotherapy and tumor immunity. Science. 2018; 362(6421):1355-1356. DOI: 10.1126/science.aav7871. View

Johnston W, Hwang R, Mattei P . Surgical considerations for neuroblastoma-associated opsoclonus-myoclonus-ataxia syndrome: a series of 14 patients from a single institution. Pediatr Surg Int. 2021; 38(2):249-255. DOI: 10.1007/s00383-021-05014-w. View

Zhang S, Zhang W, Jin M, Sun Q, Zhang Z, Qin H . Biological features and clinical outcome in infant neuroblastoma: a multicenter experience in Beijing. Eur J Pediatr. 2021; 180(7):2055-2063. DOI: 10.1007/s00431-021-03989-1. View

Paraboschi I, Privitera L, Kramer-Marek G, Anderson J, Giuliani S . Novel Treatments and Technologies Applied to the Cure of Neuroblastoma. Children (Basel). 2021; 8(6). PMC: 8226870. DOI: 10.3390/children8060482. View

Naranjo A, Irwin M, Hogarty M, Cohn S, Park J, London W . Statistical Framework in Support of a Revised Children's Oncology Group Neuroblastoma Risk Classification System. JCO Clin Cancer Inform. 2019; 2:1-15. PMC: 6421832. DOI: 10.1200/CCI.17.00140. View

Fischer J, Pohl A, Volland R, Hero B, Dubbers M, Cernaianu G . Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months. BMC Cancer. 2017; 17(1):520. PMC: 5543757. DOI: 10.1186/s12885-017-3493-0. View

He J, Wang F, Zhu J, Zhang R, Yang T, Zou Y . Association of potentially functional variants in the XPG gene with neuroblastoma risk in a Chinese population. J Cell Mol Med. 2016; 20(8):1481-90. PMC: 4956948. DOI: 10.1111/jcmm.12836. View

10.

Kitai Y, Kawasaki T, Sueyoshi T, Kobiyama K, Ishii K, Zou J . DNA-Containing Exosomes Derived from Cancer Cells Treated with Topotecan Activate a STING-Dependent Pathway and Reinforce Antitumor Immunity. J Immunol. 2017; 198(4):1649-1659. DOI: 10.4049/jimmunol.1601694. View

11.

Jackson H, Defamie V, Waterhouse P, Khokha R . TIMPs: versatile extracellular regulators in cancer. Nat Rev Cancer. 2016; 17(1):38-53. DOI: 10.1038/nrc.2016.115. View

12.

Nakamura H, Koziolova E, Chytil P, Tsukigawa K, Fang J, Haratake M . Pronounced Cellular Uptake of Pirarubicin versus That of Other Anthracyclines: Comparison of HPMA Copolymer Conjugates of Pirarubicin and Doxorubicin. Mol Pharm. 2016; 13(12):4106-4115. DOI: 10.1021/acs.molpharmaceut.6b00697. View

13.

Zhang R, Fang Y, Wu D, Lin Y, Zhang B, Liu M . Comparison of the Efficacy of Minimally Invasive and Open Surgery on Children with Neuroblastoma: A Meta-Analysis. J Laparoendosc Adv Surg Tech A. 2021; 31(7):829-838. DOI: 10.1089/lap.2020.0618. View

14.

Verly I, van Kuilenburg A, Abeling N, Goorden S, Fiocco M, Vaz F . Catecholamines profiles at diagnosis: Increased diagnostic sensitivity and correlation with biological and clinical features in neuroblastoma patients. Eur J Cancer. 2017; 72:235-243. DOI: 10.1016/j.ejca.2016.12.002. View

15.

Liu P, Yu H, Sun Y, Zhu M, Duan Y . A mPEG-PLGA-b-PLL copolymer carrier for adriamycin and siRNA delivery. Biomaterials. 2012; 33(17):4403-12. DOI: 10.1016/j.biomaterials.2012.02.041. View

16.

Tong C, Wu W, Loong H, Cho W, To K . Drug combination approach to overcome resistance to EGFR tyrosine kinase inhibitors in lung cancer. Cancer Lett. 2017; 405:100-110. DOI: 10.1016/j.canlet.2017.07.023. View

17.

Dubois S, Bagatell R . Improving Outcomes in Children With High-Risk Neuroblastoma: The Role of Randomized Trials. J Clin Oncol. 2021; 39(23):2525-2527. PMC: 8330963. DOI: 10.1200/JCO.21.01066. View

18.

Soriano A, Masanas M, Boloix A, Masia N, Paris-Coderch L, Piskareva O . Functional high-throughput screening reveals miR-323a-5p and miR-342-5p as new tumor-suppressive microRNA for neuroblastoma. Cell Mol Life Sci. 2019; 76(11):2231-2243. PMC: 6502783. DOI: 10.1007/s00018-019-03041-4. View

19.

Kim C, Choi K . Potential Roles of Iridoid Glycosides and Their Underlying Mechanisms against Diverse Cancer Growth and Metastasis: Do They Have an Inhibitory Effect on Cancer Progression?. Nutrients. 2021; 13(9). PMC: 8466600. DOI: 10.3390/nu13092974. View

20.

Arumugam P, Subramanian R, Priyadharsini J, Gopalswamy J . Thymoquinone inhibits the migration of mouse neuroblastoma (Neuro-2a) cells by down-regulating MMP-2 and MMP-9. Chin J Nat Med. 2017; 14(12):904-912. DOI: 10.1016/S1875-5364(17)30015-8. View