https://doi.org/10.4081/ejh.2021.3264
Identification of abnormally high expression of POGZ as a new biomarker associated with a poor prognosis in osteosarcoma
Submitted: 17 April 2021
Accepted: 9 July 2021
Published: 3 September 2021
Accepted: 9 July 2021
Abstract Views: 925
PDF: 496
Supplementary: 97
HTML: 13
Supplementary: 97
HTML: 13
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Osteosarcoma (OS) is the most prevalent malignant bone tumor in children and young adults. There is an urgent need for a novel biomarker related to the prognosis of OS. We performed a meta-analysis incorporating six independent datasets and performed a survival analysis with one independent dataset GSE21257 in the GEO database for gene screening. The results revealed that one potential biomarker related to OS survival, POGZ was the most significantly upregulated gene. We also verified that the POGZ was overexpressed in clinical samples. The survival analysis revealed that POGZ is associated with a poor prognosis in OS. Moreover, flow cytometry analysis of isolated OS cells demonstrated that OS cells were arrested in the G1 phase after POGZ knockdown. The RNA-seq results indicated that POGZ was co-expressed with CCNE1 and CCNB1. Pathway analysis showed that genes associated with high expression levels of POGZ were related to the cell cycle pathway. A cell model was constructed to detect the effects of POGZ. After POGZ knockdown, OS cell proliferation, invasion and migration were all decreased. Therefore, POGZ is an important gene for evaluating the prognosis of OS patients and is a potential therapeutic target.
Li Y, Nakka M, Kelly AJ, Lau CC, Krailo M, Barkauskas DA, et al. p27 is a candidate prognostic biomarker and metastatic promoter in osteosarcoma. Cancer Res 2016;76:4002-11.
DOI: https://doi.org/10.1158/0008-5472.CAN-15-3189
Gianferante DM, Mirabello L, Savage SA. Germline and somatic genetics of osteosarcoma - connecting aetiology, biology and therapy. Nat Rev Endocrinol 2017;13:480-91.
DOI: https://doi.org/10.1038/nrendo.2017.16
Rickel K, Fang F, Tao J. Molecular genetics of osteosarcoma. Bone 2017;102:69-79.
DOI: https://doi.org/10.1016/j.bone.2016.10.017
Tao T, Shen Q, Luo J, Xu Y, Liang W. MicroRNA-125a regulates cell proliferation via directly targeting E2F2 in osteosarcoma. Cell Physiol Biochem 2017;43:768-74.
DOI: https://doi.org/10.1159/000481560
Yoshida A, Fujiwara T, Uotani K, Morita T, Kiyono M, Yokoo S, et al. Clinical and functional significance of intracellular and extracellular microRNA-25-3p in osteosarcoma. Acta Med Okayama 2018;72:165-74.
Ma C, Nie XG, Wang YL, Liu XH, Liang X, Zhou QL, et al. CBX3 predicts an unfavorable prognosis and promotes tumorigenesis in osteosarcoma. Mol Med Rep 2019;19:4205-12.
DOI: https://doi.org/10.3892/mmr.2019.10104
Aran V, Devalle S, Meohas W, Heringer M, Cunha Caruso A, Pinheiro Aguiar D, et al. Osteosarcoma, chondrosarcoma and Ewing sarcoma: Clinical aspects, biomarker discovery and liquid biopsy. Crit Rev Oncol Hematol 2021;162:103340.
DOI: https://doi.org/10.1016/j.critrevonc.2021.103340
Tian H, Zhou T, Chen H, Li C, Jiang Z, Lao L, et al. Bone morphogenetic protein-2 promotes osteosarcoma growth by promoting epithelial-mesenchymal transition (EMT) through the Wnt/β-catenin signaling pathway. J Orthop Res 2019;37:1638-48.
DOI: https://doi.org/10.1002/jor.24244
Petryszak R, Burdett T, Fiorelli B, Fonseca NA, Gonzalez-Porta M, Hastings E, et al. Expression Atlas update--a database of gene and transcript expression from microarray- and sequencing-based functional genomics experiments. Nucleic Acids Res 2014;42(Database issue):D926-32.
DOI: https://doi.org/10.1093/nar/gkt1270
Han G, Wang Y, Bi W. C-Myc overexpression promotes osteosarcoma cell invasion via activation of MEK-ERK pathway. Oncol. Res 2012;20:149-56.
DOI: https://doi.org/10.3727/096504012X13522227232237
Chen D, Zhao Z, Huang Z, Chen DC, Zhu XX, Wang YZ, et al. Super enhancer inhibitors suppress MYC driven transcriptional amplification and tumor progression in osteosarcoma. Bone Res 2018;6:11.
DOI: https://doi.org/10.1038/s41413-018-0009-8
Muff R, Ram Kumar RM, Botter SM, Born W, Fuchs B. Genes regulated in metastatic osteosarcoma: evaluation by microarray analysis in four human and two mouse cell line systems. Sarcoma 2012;2012:937506.
DOI: https://doi.org/10.1155/2012/937506
Mohamed FEA, Khalil EZI, Toni NDM, Correction to: Caveolin-1 expression together with VEGF can be a predictor for lung metastasis and poor prognosis in osteosarcoma. Pathol Oncol Res 2020;26:2013-4.
DOI: https://doi.org/10.1007/s12253-019-00790-2
Isakoff MS, Bielack SS, Meltzer P, Gorlick R. Osteosarcoma: Current treatment and a collaborative pathway to success. J Clin Oncol 2015;33:3029-35.
DOI: https://doi.org/10.1200/JCO.2014.59.4895
Sadikovic B, Yoshimoto M, Al-Romaih K, Maire G, Zielenska M, Squire JA. In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma. PLoS One 2008;3:e2834.
DOI: https://doi.org/10.1371/journal.pone.0002834
Sadikovic B, Yoshimoto M, Chilton-MacNeill S, Thorner P, Squire JA, Zielenska M. Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling. Hum Mol Genet 2009;18:1962-75.
DOI: https://doi.org/10.1093/hmg/ddp117
Fritsche-Guenther R, Noske A, Ungethüm U, Kuban RJ, Schlag PM, Tunn PU, et al. De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway. Histopathology 2010;57:836-50.
DOI: https://doi.org/10.1111/j.1365-2559.2010.03713.x
Paoloni M, Davis S, Lana S, Withrow S, Sangiorgi L, Picci P, et al. Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression. BMC Genomics 2009;10:625.
DOI: https://doi.org/10.1186/1471-2164-10-625
Kuijjer ML, Peterse EF, van den Akker BE, Briaire-de Bruijn IH, Serra M, Meza-Zepeda LA, et al. IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma. BMC Cancer 2013;13:245.
DOI: https://doi.org/10.1186/1471-2407-13-245
Kuijjer ML, van den Akker BE, Hilhorst R, Mommersteeg M, Buddingh EP, Serra M, et al. Kinome and mRNA expression profiling of high-grade osteosarcoma cell lines implies Akt signaling as possible target for therapy. BMC Med Genomics 2014;7:4.
DOI: https://doi.org/10.1186/1755-8794-7-4
Buddingh EP, Ruslan SEN, Reijnders CMA, Szuhai K, Kuijjer ML, Roelofs H, et al. Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture. Clin Sarcoma Res 2015;5:16.
DOI: https://doi.org/10.1186/s13569-015-0031-1
Buddingh EP, Kuijjer ML, Duim RA, Bürger H, Agelopoulos K, Myklebost O, et al. Tumor-infiltrating macrophages are associated with metastasis suppression in high-grade osteosarcoma: a rationale for treatment with macrophage activating agents. Clin Cancer Res 2011;17:2110-9.
DOI: https://doi.org/10.1158/1078-0432.CCR-10-2047
Azim HA Jr, Peccatori FA, Brohée S, Branstetter D, Loi S, Viale G, et al. RANK-ligand (RANKL) expression in young breast cancer patients and during pregnancy. Breast Cancer Res 2015;17:24.
DOI: https://doi.org/10.1186/s13058-015-0538-7
Ho XD, Phung P, Q Le V, H Nguyen V, Reimann E, Prans E, et al. Whole transcriptome analysis identifies differentially regulated networks between osteosarcoma and normal bone samples. Exp Biol Med (Maywood) 2017;242:1802-11.
DOI: https://doi.org/10.1177/1535370217736512
Ho XD, Nguyen HG, Trinh LH, Reimann E, Prans E, Kõks G, et al. Analysis of the expression of repetitive DNA elements in osteosarcoma. Front Genet 2017;8:193.
DOI: https://doi.org/10.3389/fgene.2017.00193
Nozawa RS, Nagao K, Masuda HT, Iwasaki O, Hirota T, Nozaki N, et al. Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms through Aurora B activation. Nat Cell Biol 2010;12:719-27.
DOI: https://doi.org/10.1038/ncb2075
Ibaraki K, Hamada N, Iwamoto I, Ito H, Kawamura N, Morishita R, et al. Expression analyses of POGZ, a responsible gene for neurodevelopmental disorders, during mouse brain development. Dev Neurosci 2019;41:139-48.
DOI: https://doi.org/10.1159/000502128
Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol 2019;29:212-26.
DOI: https://doi.org/10.1016/j.tcb.2018.12.001
Engeland K. Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM. Cell Death Differ 2018;25:114-32.
DOI: https://doi.org/10.1038/cdd.2017.172
Tanaka M, Setoguchi T, Hirotsu M, Gao H, Sasaki H, Matsunoshita Y, et al. Inhibition of Notch pathway prevents osteosarcoma growth by cell cycle regulation. Br J Cancer 2009;100:1957-65.
DOI: https://doi.org/10.1038/sj.bjc.6605060
Shen JH, Qu CB, Chu HK, Cui MY, Wang YL, Sun YX, et al. siRNA targeting TCTP suppresses osteosarcoma cell growth and induces apoptosis in vitro and in vivo. Biotechnol Appl Biochem 2016;63:5-14.
DOI: https://doi.org/10.1002/bab.1335
Xie B, Wang S, Jiang N, Li JJ. Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance. Cancer Lett 2019;443:56-66.
DOI: https://doi.org/10.1016/j.canlet.2018.11.019
Möröy T, Geisen C. Cyclin E. Int J Biochem Cell Biol 2004;36:1424-39.
DOI: https://doi.org/10.1016/j.biocel.2003.12.005
Supporting Agencies
Natural Science Research Program of Jiangxi (No. 20202ACBL206012. to XC), National Natural Science Foundation of China (No. 81660357 to XC), National Natural Science Foundation of China (No. 81860397 to XC)How to Cite
Zheng, S., Liu, Y., Sun, H., Jia, . J., Wu, T., Ding, R., & Cheng, X. (2021). Identification of abnormally high expression of POGZ as a new biomarker associated with a poor prognosis in osteosarcoma. European Journal of Histochemistry, 65(3). https://doi.org/10.4081/ejh.2021.3264
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
