FEATURES OF THE EXPRESSION OF MATRICELLULAR GENES (OSTEOPONTIN AND OSTEONECTIN) IN BENIGN AND MALIGNANT TUMORS OF THE PROSTATIC GLAND
T. Zadvornyi1, N. Lukianova1, T. Borikun1, O. Kashuba1, E. Stakhovsky2, Yu. Vitruk2, A. Tymoshenko1, O. Mushii1, L. Kovalevska1, V. Chekhun1
1 RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Ukraine
2 National Cancer Institute, Kyiv, Ukraine
DOI: https://doi.org/10.15407/oncology.2023.01.047
Summary. Prostate cancer (PCa) is one of the most common oncological diseases in men both in Ukraine and in the world, which determines the need to search for new diagnostic and prognostic markers. According to the data of modern literature, a characteristic feature of malignant growth and progression is the remodeling of the extracellular matrix on the background of an increase in the expression of matricellular proteins (MCP). Aim: to conduct a comparative study of the expression of matricellular genes at the level of mRNA (SPP1 and SPARC) and protein (OPN and ON) in the tissue of benign and malignant tumors of the prostate gland. Objects ОРИГІНАЛЬНІ ДОСЛІДЖЕННЯ 5 4 ОНКОЛОГІЯ • Т. 25 • № 1 • 2023 Одержано: 25.04.2023 and methods: the work is based on the analysis of the results of examination and treatment of 50 patients with stage II–III prostate cancer and 20 patients with benign prostatic hyperplasia (BPH), who were treated during 2015–2021 at the National Cancer Institute of the Ministry of Health of Ukraine. The study of the expression of matricellular genes at the level of mRNA and protein in the PCa and BPH tissues was carried out using the methods of real-time polymerase chain reaction and immunohistochemistry, respectively. The bioinformatical study of SPP1 and SPARC expression in the tissue of BPH and PCa was carried out using the сamсАРP resource on the Cambridge Dataset (2015). The analysis of the recurrence-free survival rates of patients with PCa depending on the expression of SPP1 and SPARC was carried out using the PROGgeneV2 (GSE40272 Dataset). Statistical analysis was performed using GraphPad Prism v. 8.00. Results: the analysis of the results of the immunohistochemical study of the MCP established that the PCa tissue is characterized by a high level of OPN and ON. It has been demonstrated that the level of ON expression in the PCa tissue is 2.5 (p < 0.05) times higher compared to BPH tissue. It was found that the level of SPP1 and SPARC in the PCa tissue was 3.9 (p < 0.05) and 28.9 (p < 0.05) times higher compared to the corresponding expression indicators of the studied genes in the tissue of the BPH. It is shown that the rate of recurrence-free 5-year survival decreased by 20.0% (p < 0.05) in patients with PCa with a high level of SPARC mRNA in the tumor tissue. Conclusions: the obtained results indicate the need for further study of the role of MCP genes in the mechanisms of the development of PCa with the aim of using these indicators as markers for the differential diagnosis of the tumor process.
Keywords: prostate cancer, benign prostatic hyperplasia, osteopontin, osteonectin, SPP1, SPARC
References
- Gordon-Weeks A, Yuzhalin Cancer extracellular matrix proteins regulate tumour immunity. Cancers 2020; 12 (11): 3331. doi: 10.3390/cancers12113331
- Gopinath P, Natarajan A, Sathyanarayanan A, et al. The multifaceted role of Matricellular Proteins in health and cancer, as biomarkers and therapeutic Gene 2022; 815: 146137. doi: 10.1016/j.gene.2021.146137
- Chiodoni C, Colombo MP, Sangaletti Matricellular pro- teins: from homeostasis to infl tion, cancer, and metastasis. Cancer Metastasis Rev 2010; 29: 295–307. doi: 10.1007/s10555-010-9221-8
- Gerarduzzi C, Hartmann U, Leask A, et al. The matrix revo- lution: matricellular proteins and restructuring of the cancer micro Cancer Res 2020; 80 (13): 2705–17. doi: 10.1158/0008-5472.CAN-18-2098
- Thakur R, Mishra DP. Matrix reloaded: CCN, tenascin and SIBLING group of matricellular proteins in orchestrating cancer hallmark c Pharmacol Ther 2016; 168: 61–74. doi: 10.1016/j.pharmthera.2016.09.002
- Sodek J, Zhu B, Huynh MH, et al. Novel functions of the matricellular proteins osteopontin and osteonectin/ Connect Tissue Res 2002; 43 (2–3): 308–19. doi: 10.1080/03008200290001050
- Viloria K, Hill Embracing the complexity of matricel- lular proteins: the functional and clinical significance of splice variation. Biomol Concepts 2016; 7 (2): 117–32. doi: 10.1515/bmc-2016-0004
- Wu T, Ouyang Matricellular proteins: multifaceted extra- cellular regulators in tumor dormancy. Protein Cell 2014; 5 (4): 249–52. doi: 10.1007/s13238-014-0023-6
- Desai B, Rogers MJ, Chellaiah MA. Mechanisms of osteo- pontin and CD44 as metastatic principles in prostate cancer Mol Cancer 2007; 6: 1–16. doi: 10.1186/1476-4598- 6-18
- Al-Wadi AH, Al-A’Araji SB, Ali SJ, et al. Evaluation of serum osteopontin and its relation with other biomarkers of pros- tate cancer in Iraqi AIP Conference Proceedings 2022; 2450 (1): 020015. doi: 10.1063/5.0095584
- Moorman HR, Poschel D, Klement JD, et al. Osteopon- tin: a key regulator of tumor progression and immuno- Cancers 2020; 12 (11): 3379. doi: 10.3390/ cancers12113379
- Shevde LA, Samant Role of osteopontin in the patho- physiology of cancer. Matrix Biol 2014; 37: 131–41. doi: 10.1016/j.matbio.2014.03.001
- Trotter TN, Yang Y. Matricellular proteins as regulators of cancer metastasis to Matrix Biol 2016; 52: 301–14. doi: 10.1016/j.matbio.2016.01.006
- Mateo F, Meca-Cortés Ó, Celià-Terrassa T, et al. SPARC mediates metastatic cooperation between CSC and non- CSC prostate cancer cell Mol Cancer 2014; 13: 1–17. doi: 10.1186/1476-4598-13-237
- Jacob K, Webber M, Benayahu D, et al. Osteonectin pro- motes prostate cancer cell migration and invasion: a possible mechanism for metastasis to bone. Cancer Res 1999; 59 (17): 4453–7. PMID: 10485497
- Yu A, Guo K, Qin Q, et al. Clinicopathological and prog- nostic signifi ance of osteopontin expression in patients with prostate cancer: a systematic review and meta-analysis. Biosci Rep 2021; 41 (8): BSR20203531. doi: 10.1042/ BSR20203531
- Sharma S, Xing F, Liu Y, et al. Secreted protein acidic and rich in cysteine (SPARC) mediates metastatic dormancy of prostate cancer in J Biol Chem 2016; 291 (37), 19351–63. doi: 10.1074/jbc.M116.737379
- Said N, Frierson HF, Chernauskas D, et al. The role of SPARC in the TRAMP model of prostate carcinogenesis and Oncogene 2009; 28 (39): 3487–98. doi: 10.1038/onc.2009.205
- Sharma S, Xing F, Liu Y, et a SPARC in tumor micro- environment induces dormancy of prostate cancer in bone. Cancer Res 2015; 75: 3206. doi: 10.1158/1538-7445. AM2015-3206
- Nakamura KDM, Tilli TM, Wanderley JL, et al. Osteopontin splice variants expression is involved on docetaxel resistance in PC3 prostate cancer c Tumor Biol 2016; 37: 2655–63. doi: 10.1007/s13277-015-4095-6
- Popovics P, Awadallah WN, Kohrt SE, et al. Prostatic osteo- pontin expression is associated with symptomatic benign prostatic The Prostate 2020; 80 (10): 731–41. doi: 10.1002/pros.23986
- Zhang JD, Ruschhaupt M, Biczok 2013. ddCt method for qRT–PCR data analysis. https://citeseerx.ist.psu.edu/pdf/63727bfe6cc3467c2a02e0816e6451ef242b481b
- McClelland RA, Wilson D, Leake R, et al. A multicentre study into the reliability of steroid receptor immunocytochemical assay quantific British Quality Control Group. Eur J Cancer 1991; 27 (6): 711–5. doi: 10.1016/0277-5379(91) 90171-9
- Thalmann GN, Sikes RA, Devoll RE, et al. Osteopontin: possible role in prostate cancer progression. Clin Cancer Res 1999, 5 (8): 2271–77. PMID: 10473115
- Tilli TM, Thuler LC, Matos AR, et al. Expression analysis of osteopontin mRNA splice variants in prostate cancer and benign prostatic Exp Mol Pathol 2012; 92 (1): 13–9. doi: 10.1016/j.yexmp.2011.09.014;
- Forootan SS, Foster CS, Aachi VR, et al. Prognostic signifi- cance of osteopontin expression in human prostate can- Int J Cancer 2006; 118 (9): 2255–61. doi: 10.1002/ ij 1619
- Thomas S, Waterman P, Chen S, et al. Development of se- creted protein and acidic and rich in cysteine (SPARC) targeted nanoparticles for the prognostic molecular imaging of metastatic prostate cancer. J Nanomed Nanotechnol 2011; 2 (112): 2157-7439-2-112. doi: 4172/2157-7439. 1000112
- Danasekaran SM, Barrette TR, Ghosh Delineation of prognostic biomarkers in prostate cancer metastasis. Nature 2001; 412 (6849): 822–6. doi: 10.1038/35090585
No comments » Add comment