CRIP-1 OVEREXPRESSION-PROGNOSTIC FACTOR IN CHILDREN’S OSTEOSARCOMA?

Authors

  • A. IVAN Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • N. FORNA Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Luminita IVAN “Dr. Iacob Czihac” Military Emergency Clinical Hospital from Iasi, Romania
  • Cristina MORARIU “Dr. Iacob Czihac” Military Emergency Clinical Hospital from Iasi, Romania
  • Mioara Calipsoana MATEI Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • P.D. SIRBU Grigore T. Popa” University of Medicine and Pharmacy Iasi

DOI:

https://doi.org/10.22551/MSJ.2024.02.07

Abstract

Predicting the clinical evolution of patients with osteosarcoma is an essential condition for personalized treatment. In researching new and reliable biomarkers we identified CRIP-1 (Cysteine-Rich Intestinal Protein 1). Its overexpression has been documented to have a significant prognostic impact on gastric and colorectal cancer. Therefore, we aimed to investigate the overexpression of CRIP-1 in pediatric osteosarcoma and assess its potential as a prognostic biomarker. Materials and methods: We analyzed 65 samples from patients diagnosed with osteosarcoma at “Sf. Maria” Emergency Clinical Hospital for Children from Iasi, between 2017 and 2021. Two staining kits were used: Mouse and Rabbit Specific HRP/DAB (ABC) Detection IHC Kit from Abcam and Novolink Poly HRP Kit. Results: CRIP-1 was over expressed in 92.6% of the cases. The lower the degree of differentiation, the less CRIP-1 is over expressed and the more frequently it is found in the nucleus. Conclusions: Could this mean that CRIP-1 overexpression is associated with a better prognosis? The study highlights the clinical implications of CRIP-1 in osteosarcoma, emphasizing its importance for prognosis, and personalized treatment strategies. However, it calls for further investigation into CRIP-1 role in cancer biology (molecular pathways and interactions with other prognostic factors).

Author Biographies

  • A. IVAN, Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Surgery (II)

  • N. FORNA, Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Surgery (II)

  • Mioara Calipsoana MATEI, Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Preventive Medicine and Interdisciplinarity
    “Dr. Iacob Czihac” Military Emergency Clinical Hospital from Iasi, Romania

  • P.D. SIRBU, Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Surgery (II)

References

1. Bovée JVMG. Bone Tumors. In: Longacre TA, Greenson JK, Hornick KJL, Reuter VE (eds.) Mills and Sternberg’s Diagnostic Surgical Pathology. 7th Edition, volume 1, Lippincott Williams & Wilkins (LWW) Publishing House, 2022, 279-322.
2. ESMO / European Sarcoma Network Working Group. Bone Sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012; 25(Suppl. 3): iii113–iii12 / doi:10.1093/ annonc/mdu256.
3. Van der Wonde HJ, Kroon HMJA. Radiologic approach of skeletal tumors. In: Hogendoorn PCW, Bovee JVMG (eds). Practical, Clinical, Radiological and Pathological Diagnosis of Skeletal Tumors. Leiden, Boerhaave Committee for Postgraduate Education in Medicine 2012, 15-31.
4. ***WHO Classification of Tumors Editorial Board. WHO Classification of Tumors. Soft Tissue and Bone Tumours 5th edition, volume 3, 2020, 391-421.
5. Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A, Picci P. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy. Cancer 2006; 106: 1154-1161 / doi: 10.1002/ cncr.21724
6. Grimer R, Athanasou N, Gerrand C, et al. UK guidelines for management of bone sarcoma. Sarcoma 2010; 317-462.
7. Hauben El, Weeden S, Pringle J, et al. Does the histological subtype of high-grade central osteosar-coma, influence the response of treatment with chemotherapy and does it affect overall survival? A study of 570 patients of two consecutive trials of the European Osteosarcoma Intergroup. Eur J Cancer 2002; 38: 1218-1225.
8. Unni KK, Inwards CY. Dahlin’s bone tumors: general aspects and data on 10165 cases. 6th Edition, Lippincott Raven, Philadelphia, 2012.
9. Baumhoer D, Elsner M, Smida J, et al. CRIP1 expression is correlated with a favorable outcome and less metastases in osteosarcoma patients. Oncotarget 2011; 2(12): 970-975 / doi: 10.18632/oncotarget.398.
10. He G, Zhu H, Yao Y, et al. Cysteine-rich intestinal protein 1 silencing alleviates the migration and invasive capability enhancement induced by excessive zinc supplementation in colorectal cancer cells. Am J Transl Res 2019; 11(6): 3578-3588.
11. Lanningham-Foster L, Green CL, Langkamp-Henken B, Davis BA, Nguyen KT, Bender BS, Cousins RJ. Overexpression of CRIP in transgenic mice alters cytokine patterns and the immune response. Am J Physiol Endocrinol Metab 2002; 282(6): E1197-E1203 / doi: 10.1152/ ajpendo.00508.2001.
12. Sun H, Zhou R, Zheng Y, Wen Z, et al. CRIP1 cooperates with BRCA2 to drive the nuclear enrichment of RAD51 and to facilitate homologous repair upon DNA damage induced by chemotherapy. Oncogene 2021; 40(34): 5342-5355 / doi: 10.1038/s41388-021-01932-0.
13. Ludyga N, Englert S, Pflieger K, et al. The impact of Cysteine-rich intestinal protein 1 (CRIP1) in human breast cancer. Mol Cancer 2013; 12: 28 / doi: 10.1186/1476-4598-12-28.
14. Zhang L, Zhou R, Zhang W, et al. Cysteine-rich intestinal protein 1 suppresses apoptosis and chemo-sensitivity to 5-fluorouracil in colorectal cancer through ubiquitin-mediated Fas degradation. J Exp Clin Cancer Res 2019; 38(1): 120 / doi: 10.1186/s13046-019-1117-z.
15. Zhang LZ, Huang LY, Huang AL, Liu JX, Yang F. CRIP1 promotes cell migration, invasion and epithelial-mesenchymal transition of cervical cancer by activating the Wnt/β‑catenin signaling pathway. Life Sciences 2018; 207: 420-427 / doi: 10.1016/j.lfs.2018.05.054.
16. Qi B, Liu S, Liu D, Yao H, Yan R. Comprehensive Analysis of CRIP1 in Patients with Ovarian Can-cer, including ceRNA Network, Immune-Infiltration Pattern, and Clinical Benefit. Dis Markers 2022; 2022: 2687867 / doi: 10.1155/2022/2687867.
17. Liu Y, Li W, Luo J, et al. Cysteine-Rich Intestinal Protein 1 Served as an Epithelial Ovarian Cancer Marker via Promoting Wnt/β-Catenin-Mediated EMT and Tumor Metastasis. Dis Markers 2021; 2021: 3566749 / doi: 10.1155/2021/3566749.
18. Li HG, Zhao LH, Zhang ZH, et al. The impact of Cysteine-rich intestinal protein 1 (CRIP1) on thyroid carcinoma. Cell Physiol Biochem 2017; 43(5): 2037-2046 / doi: 10.1159/000484184.
19. Liu X, Tang R, Xu J, et al. CRIP1 fosters MDSC trafficking and resets tumour microenvironment via facilitating NF-κB/p65 nuclear translocation in pancreatic ductal adenocarcinoma. Gut 2023; 72(12): 2329-2343 / doi: 10.1136/gutjnl-2022-329349.
20. Wang Q, Williamson M, Bott S, et al. Hypomethylation of WNT5A, CRIP1 and S100P in prostate cancer. Oncogene 2007; 26 (45): 6560-6565 / doi: 10.1038/sj.onc.1210472.
21. Yu H, Meng X, Wu J, et al. Cryptochrome 1 Overexpression Correlates with Tumor Progression and Poor Prognosis in Patients with Colorectal Cancer. PLoS ONE 2013; 8(4): e61679.
22. Southekal S, Shakyawar SK, Bajpai P, et al. Molecular Subtyping and Survival Analysis of Osteosar-coma Reveals Prognostic Biomarkers and Key Canonical Pathways. Cancers. 2023; 15(7): 2134 / doi: 10.3390/cancers15072134.
23. Xu Y, Shi F, Zhang Y, Yin M, Han X, Feng J, Wang G. Twenty-year outcome of prevalence, inci-dence, mortality and survival rate in patients with malignant bone tumors. Int J Cancer 2024; 154(2): 226-240/ doi: 10.1002/ijc.34694.
24. Misaghi A, Goldin A, Awad M, Kulidjian AA. Osteosarcoma: a comprehensive review. SICOT-J 2018; 4: 8 / doi: 10.1051/sicotj/2017028.
25. Lambropoulou M, Deftereou TE, Kynigopoulos S, et al. Co-expression of galectin-3 and CRIP-1 in endometrial cancer: prognostic value and patient survival. Med Oncol 2016; 33(1): 8 / doi: 10.1007/ s1 2032-015-0723-7.

Additional Files

Published

2024-06-28