YY1 Overexpression is Associated with Poor Prognosis and Metastasis-free Survival in Patients Suffering Osteosarcoma

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2011 Nov 4

PMID 22047406

Citations 22

Authors

Filomena de Nigris

Licciana Zanella

Francesco Cacciatore

Anna De Chiara

Flavio Fazioli

Gennaro Chiappetta

Gaetano Apice

Teresa Infante

Mario Monaco

Raffaele Rossiello

Gaetano De Rosa

Marco Alberghini

Claudio Napoli

Affiliations

Soon will be listed here.

Abstract

Background: The polycomb transcription factor Yin Yang 1 (YY1) overexpression can be causally implicated in experimental tumor growth and metastasization. To date, there is no clinical evidence of YY1 involvement in outcome of patients with osteosarcoma. Prognosis of osteosarcoma is still severe and only few patients survive beyond five years. We performed a prospective immunohistochemistry analysis to correlate YY1 immunostaining with metastatic development and survival in a selected homogeneous group of patients with osteosarcoma.

Methods: We studied 41 patients suffering from osteosarcoma (stage II-IVa). Multivariate analysis was performed using Cox proportional hazard regression to evaluate the correlation between YY1 expression and both metastasis development and mortality.

Results: YY1 protein is not usually present in normal bone; in contrast, a high number of patients (61%) showed a high score of YY1 positive cells (51-100%) and 39% had a low score (10-50% positive cells). No statistical difference was found in histology, anatomic sites, or response to chemotherapy between the two degrees of YY1 expression. Cox regression analysis demonstrated that the highest score of YY1 expression was predictive of both low metastasis-free survival (HR = 4.690, 95%CI = 1.079-20.396; p = 0.039) and poor overall survival (HR = 8.353, 95%CI = 1.863-37.451 p = 0.006) regardless of the effects of covariates such as age, gender, histology and chemonecrosis.

Conclusion: Overexpression of YY1 in primary site of osteosarcoma is associated with the occurrence of metastasis and poor clinical outcome.

Citing Articles

Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1.

Dillen A, Bui I, Jung M, Agioti S, Zaravinos A, Bonavida B Cancers (Basel). 2024; 16(6).

PMID: 38539569 PMC: 10968822. DOI: 10.3390/cancers16061237.

Metformin alleviates adriamycin resistance of osteosarcoma by declining YY1 to inhibit MDR1 transcriptional activity.

Wu B, Li P, Qiu E, Chen J BMC Pharmacol Toxicol. 2023; 24(1):50.

PMID: 37828612 PMC: 10571298. DOI: 10.1186/s40360-023-00685-8.

Targeting Transcription Factor YY1 for Cancer Treatment: Current Strategies and Future Directions.

Hosea R, Hillary S, Wu S, Kasim V Cancers (Basel). 2023; 15(13).

PMID: 37444616 PMC: 10340792. DOI: 10.3390/cancers15133506.

Dissecting the roles and clinical potential of YY1 in the tumor microenvironment.

Li M, Wei J, Xue C, Zhou X, Chen S, Zheng L Front Oncol. 2023; 13:1122110.

PMID: 37081988 PMC: 10110844. DOI: 10.3389/fonc.2023.1122110.

Development and Validation of a Prognostic Model for Overall Survival in Patients with Primary Pelvis and Spine Osteosarcoma: A Population-Based Study and External Validation.

Wang D, Liu F, Li B, Xu J, Gong H, Yang M J Clin Med. 2023; 12(7).

PMID: 37048606 PMC: 10095419. DOI: 10.3390/jcm12072521.

References

Chinnappan D, Xiao D, Ratnasari A, Andry C, King T, Weber H . Transcription factor YY1 expression in human gastrointestinal cancer cells. Int J Oncol. 2009; 34(5):1417-23. View

Zaravinos A, Spandidos D . Yin yang 1 expression in human tumors. Cell Cycle. 2010; 9(3):512-22. DOI: 10.4161/cc.9.3.10588. View

Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G . Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev. 2006; 32(6):423-36. DOI: 10.1016/j.ctrv.2006.05.005. View

Baldini N, Scotlandi K, Barbanti-Brodano G, Manara M, Maurici D, Bacci G . Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N Engl J Med. 1995; 333(21):1380-5. DOI: 10.1056/NEJM199511233332103. View

Bielack S, Kempf-Bielack B, Delling G, Exner G, Flege S, Helmke K . Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002; 20(3):776-90. DOI: 10.1200/JCO.2002.20.3.776. View

Bacci G, Longhi A, Ferrari S, Lari S, Manfrini M, Donati D . Prognostic significance of serum alkaline phosphatase in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: recent experience at Rizzoli Institute. Oncol Rep. 2001; 9(1):171-5. View

Kim M, Lee S, Lee T, Cho W, Song W, Koh J . Prognostic nomogram for predicting the 5-year probability of developing metastasis after neo-adjuvant chemotherapy and definitive surgery for AJCC stage II extremity osteosarcoma. Ann Oncol. 2009; 20(5):955-60. DOI: 10.1093/annonc/mdn723. View

Baritaki S, Suzuki E, Umezawa K, Spandidos D, Berenson J, Daniels T . Inhibition of Yin Yang 1-dependent repressor activity of DR5 transcription and expression by the novel proteasome inhibitor NPI-0052 contributes to its TRAIL-enhanced apoptosis in cancer cells. J Immunol. 2008; 180(9):6199-210. PMC: 3747671. DOI: 10.4049/jimmunol.180.9.6199. View

Yang J, Yang D, Sun Y, Sun B, Wang G, Trent J . Genetic amplification of the vascular endothelial growth factor (VEGF) pathway genes, including VEGFA, in human osteosarcoma. Cancer. 2011; 117(21):4925-38. PMC: 3465081. DOI: 10.1002/cncr.26116. View

10.

De Nigris F, Botti C, Rossiello R, Crimi E, Sica V, Napoli C . Cooperation between Myc and YY1 provides novel silencing transcriptional targets of alpha3beta1-integrin in tumour cells. Oncogene. 2006; 26(3):382-94. DOI: 10.1038/sj.onc.1209804. View

11.

Serra M, Scotlandi K, Reverter-Branchat G, Ferrari S, Manara M, Benini S . Value of P-glycoprotein and clinicopathologic factors as the basis for new treatment strategies in high-grade osteosarcoma of the extremities. J Clin Oncol. 2003; 21(3):536-42. DOI: 10.1200/JCO.2003.03.144. View

12.

Urakawa H, Nishida Y, Naruse T, Nakashima H, Ishiguro N . Cyclooxygenase-2 overexpression predicts poor survival in patients with high-grade extremity osteosarcoma: a pilot study. Clin Orthop Relat Res. 2009; 467(11):2932-8. PMC: 2758970. DOI: 10.1007/s11999-009-0814-x. View

13.

Tainsky M . Genomic and proteomic biomarkers for cancer: a multitude of opportunities. Biochim Biophys Acta. 2009; 1796(2):176-93. PMC: 2752479. DOI: 10.1016/j.bbcan.2009.04.004. View

14.

Laverdiere C, Hoang B, Yang R, Sowers R, Qin J, Meyers P . Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma. Clin Cancer Res. 2005; 11(7):2561-7. DOI: 10.1158/1078-0432.CCR-04-1089. View

15.

de Nigris F, Crudele V, Giovane A, Casamassimi A, Giordano A, Garban H . CXCR4/YY1 inhibition impairs VEGF network and angiogenesis during malignancy. Proc Natl Acad Sci U S A. 2010; 107(32):14484-9. PMC: 2922579. DOI: 10.1073/pnas.1008256107. View

16.

de Nigris F, Botti C, De Chiara A, Rossiello R, Apice G, Fazioli F . Expression of transcription factor Yin Yang 1 in human osteosarcomas. Eur J Cancer. 2006; 42(15):2420-4. DOI: 10.1016/j.ejca.2006.06.008. View

17.

Clark J, Dass C, Choong P . A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2007; 134(3):281-97. DOI: 10.1007/s00432-007-0330-x. View

18.

Thomassen M, Tan Q, Kruse T . Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer. BMC Cancer. 2009; 8:394. PMC: 2642844. DOI: 10.1186/1471-2407-8-394. View

19.

Napoli C, Giordano A, Casamassimi A, Pentimalli F, Ignarro L, de Nigris F . Directed in vivo angiogenesis assay and the study of systemic neoangiogenesis in cancer. Int J Cancer. 2011; 128(7):1505-8. DOI: 10.1002/ijc.25743. View

20.

Rizkallah R, Alexander K, Kassardjian A, Luscher B, Hurt M . The transcription factor YY1 is a substrate for Polo-like kinase 1 at the G2/M transition of the cell cycle. PLoS One. 2011; 6(1):e15928. PMC: 3017090. DOI: 10.1371/journal.pone.0015928. View