Generic placeholder image

Current Bioinformatics

Editor-in-Chief

ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

Bio-analytical Identification of Key Genes that Could Contribute to the Progression and Metastasis of Osteosarcoma

Author(s): Fei Wang, Guoqing Qin, Junzhi Liu, Xiunan Wang and Baoguo Ye*

Volume 16, Issue 2, 2021

Published on: 31 July, 2020

Page: [216 - 224] Pages: 9

DOI: 10.2174/1574893615999200801014939

Price: $65

Abstract

Background: Osteosarcoma (OS) is one of the most common primary malignant bone tumors in children and adolescents. OS metastasis has been a challenge in the treatment of OS. The present study screened progression related genes in OS by analyzing a public dataset GSE42352, and identified 691 up-regulated and 945 down-regulated genes in advanced stage OS compared to early-stage OS samples.

Methods: Protein-protein interaction (PPI) networks were further employed to reveal the interaction among these genes. Bioinformatics analysis showed that progression related differently expressed genes (DEGs) were significantly associated with the regulation of cell proliferation and metabolisms.

Results: This study revealed that progression related DEGs were dysregulated in metastatic OS compared to non-metastatic OS samples. Further analysis showed CSF1R, CASP1, CD163, AP1B1, LAPTM5, PEX19, SLA, STAB1, YWHAH, PLCB2, and GPR84 were associated with the metastasis-free survival time in patients with OS.

Conclusion: These findings provided novel information for us to understand the mechanisms underlying the progression and metastasis of OS.

Keywords: Osteosarcoma, metastasis, bioinformatics analysis, signaling pathway, protein, genes.

Graphical Abstract
[1]
Breneman JC, Donaldson SS, Constine L, et al. The Children’s oncology group radiation oncology discipline: 15 years of contribution to the treatment of childhood cancer Int J Radiat Oncol Biol Phys 2018; 101(4): 860-74.
[2]
Wang G, Sun M, Jiang Y, et al. Anlotinib, a novel small molecular tyrosine kinase inhibitor, suppresses growth and metastasis via dual blockade of VEGFR2 and MET in osteosarcoma. Int J Cancer 2019; 145(4): 979-93.
[http://dx.doi.org/10.1002/ijc.32180] [PMID: 30719715]
[3]
Cai Q, Zeng S, Dai X, Wu J, Ma W. miR-504 promotes tumour growth and metastasis in human osteosarcoma by targeting TP53INP1. Oncol Rep 2017; 38(5): 2993-3000.
[http://dx.doi.org/10.3892/or.2017.5983] [PMID: 29048685]
[4]
Berlanga P, Muñoz L, Piqueras M, et al. miR-200c and phospho-AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis. Mol Oncol 2016; 10(7): 1043-53.
[http://dx.doi.org/10.1016/j.molonc.2016.04.004] [PMID: 27155790]
[5]
Briccoli A, Rocca M, Salone M, Guzzardella GA, Balladelli A, Bacci G. High grade osteosarcoma of the extremities metastatic to the lung: long-term results in 323 patients treated combining surgery and chemotherapy, 1985-2005. Surg Oncol 2010; 19(4): 193-9.
[http://dx.doi.org/10.1016/j.suronc.2009.05.002] [PMID: 19515554]
[6]
Meazza C, Cefalo G, Massimino M, et al. Primary metastatic osteosarcoma: results of a prospective study in children given chemotherapy and interleukin-2. Med Oncol 2017; 34(12): 191.
[http://dx.doi.org/10.1007/s12032-017-1052-9] [PMID: 29094224]
[7]
Tanaka T, Yui Y, Naka N, et al. Dynamic analysis of lung metastasis by mouse osteosarcoma LM8: VEGF is a candidate for anti-metastasis therapy. Clin Exp Metastasis 2013; 30(4): 369-79.
[http://dx.doi.org/10.1007/s10585-012-9543-8] [PMID: 23076771]
[8]
Zhang Y, Tang YJ, Li ZH, Pan F, Huang K, Xu GH. KiSS1 inhibits growth and invasion of osteosarcoma cells through inhibition of the MAPK pathway. Eur J Histochem 2013; 57(4), e30.
[http://dx.doi.org/10.4081/ejh.2013.e30] [PMID: 24441183]
[9]
Zhang Y, Cheng H, Li W, et al. Highly-expressed P2X7 receptor promotes growth and metastasis of human HOS/MNNG osteosarcoma cells via PI3K/Akt/GSK3β/β-catenin and mTOR/HIF1α/VEGF signaling 2019; 145(4): 1068-82.
[10]
Dai J, Xu LJ, Han GD, et al. Down-regulation of long non-coding RNA ITGB2-AS1 inhibits osteosarcoma proliferation and metastasis by repressing Wnt/β-catenin signalling and predicts favourable prognosis. Artif Cells Nanomed Biotechnol 2018; 46(sup3): S783-90..
[http://dx.doi.org/10.1080/21691401.2018.1511576] [PMID: 30260245]
[11]
Maximov VV, Akkawi R, Khawaled S, et al. MiR-16-1-3p and miR-16-2-3p possess strong tumor suppressive and antimetastatic properties in osteosarcoma. Int J Cancer 2019; 145(11): 3052-63.
[http://dx.doi.org/10.1002/ijc.32368] [PMID: 31018244]
[12]
Shigematsu M, Honda S, Loher P, Telonis AG, Rigoutsos I, Kirino Y. YAMAT-seq: an efficient method for high-throughput sequencing of mature transfer RNAs. Nucleic Acids Res 2017; 45(9), e70.
[http://dx.doi.org/10.1093/nar/gkx005] [PMID: 28108659]
[13]
Dai P, He Y, Luo G, et al. Screening candidate microRNA-mRNA network for predicting the response to chemoresistance in osteosarcoma by bioinformatics analysis. J Cell Biochem 2019; 120(10): 16798-810.
[http://dx.doi.org/10.1002/jcb.28938] [PMID: 31090103]
[14]
Shi Z, Zhou H, Pan B, et al. Exploring the key genes and pathways of osteosarcoma with pulmonary metastasis using a gene expression microarray. Mol Med Rep 2017; 16(5): 7423-31.
[http://dx.doi.org/10.3892/mmr.2017.7577] [PMID: 28944885]
[15]
O’Sullivan F, Keenan J, Aherne S, et al. Parallel mRNA, proteomics and miRNA expression analysis in cell line models of the intestine. World J Gastroenterol 2017; 23(41): 7369-86.
[http://dx.doi.org/10.3748/wjg.v23.i41.7369] [PMID: 29151691]
[16]
Zúñiga-León E, Carrasco-Navarro U, Fierro F. NeVOmics: an enrichment tool for gene ontology and functional network analysis and visualization of data from omics technologies. Genes 2018; 9(12), E569.
[http://dx.doi.org/10.3390/genes9120569] [PMID: 30477135]
[17]
Ágg B, Császár A, Szalay-Bekő M, et al. The EntOptLayout Cytoscape plug-in for the efficient visualization of major protein complexes in protein-protein interaction and signalling networks. Bioinformatics 2019; 35(21): 4490-2.
[http://dx.doi.org/10.1093/bioinformatics/btz257] [PMID: 31004478]
[18]
Morcos F, Lamanna C, Sikora M, Izaguirre J. Cytoprophet: a Cytoscape plug-in for protein and domain interaction networks inference. Bioinformatics 2008; 24(19): 2265-6.
[http://dx.doi.org/10.1093/bioinformatics/btn380] [PMID: 18653520]
[19]
Xing C, Cai Z, Gong J, Zhou J, Xu J, Guo F. Identification of potential biomarkers involved in gastric cancer through integrated analysis of non-coding rna associated competing endogenous rnas network. Clin Lab 2018; 64(10): 1661-9.
[http://dx.doi.org/10.7754/Clin.Lab.2018.180419] [PMID: 30336538]
[20]
Wang Y, Zeng X, Wang N, et al. Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma. Mol Cancer 2018; 17(1): 89.
[http://dx.doi.org/10.1186/s12943-018-0837-6] [PMID: 29753317]
[21]
Lu J, Chen W, Liu H, Yang H, Liu T. Transcription factor CEBPB inhibits the proliferation of osteosarcoma by regulating downstream target gene CLEC5A. J Clin Lab Anal 2019; 33(9), e22985.
[http://dx.doi.org/10.1002/jcla.22985] [PMID: 31364785]
[22]
Gong Tao. MicroRNA-29a suppresses the invasion and migration of osteosarcoma cells by regulating the SOCS1/NF-κB signalling pathway through negatively targeting DNMT3B. Int J Mol Med 2019; 44(4): 1219-32.
[http://dx.doi.org/10.3892/ijmm.2019.4287]
[23]
Zhou S, Yu L, Xiong M, Dai G. LncRNA SNHG12 promotes tumorigenesis and metastasis in osteosarcoma by upregulating Notch2 by sponging miR-195-5p. Biochem Biophys Res Commun 2018; 495(2): 1822-32.
[http://dx.doi.org/10.1016/j.bbrc.2017.12.047] [PMID: 29229388]
[24]
Wang J, Lv X, Xu F, Wei M, Liu C, Yang Y. GNA14 silencing suppresses the proliferation of endometrial carcinoma cells through inducing apoptosis and G2/M cell cycle arrest. Biosci Rep 2018; 38(5), BSR20180574.
[http://dx.doi.org/10.1042/BSR20180574] [PMID: 30054423]
[25]
Zhao TT, Jin F, Li JG, et al. TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway. J Cancer 2018; 9(8): 1349-56.
[http://dx.doi.org/10.7150/jca.22390] [PMID: 29721043]
[26]
Yao Z, Han L, Chen Y, et al. Hedgehog signalling in the tumourigenesis and metastasis of osteosarcoma, and its potential value in the clinical therapy of osteosarcoma. Cell Death Dis 2018; 9(6): 701.
[http://dx.doi.org/10.1038/s41419-018-0647-1] [PMID: 29899399]
[27]
Kumar RM, Fuchs B. Hedgehog signaling inhibitors as anti-cancer agents in osteosarcoma. Cancers 2015; 7(2): 784-94.
[http://dx.doi.org/10.3390/cancers7020784] [PMID: 25985215]
[28]
Huang T, Zhang P, Li W, et al. G9A promotes tumor cell growth and invasion by silencing CASP1 in non-small-cell lung cancer cells. Cell Death Dis 2017; 8(4), e2726.
[http://dx.doi.org/10.1038/cddis.2017.65] [PMID: 28383547]
[29]
Dietrich PA, Yang C, Leung HH, et al. GPR84 sustains aberrant β-catenin signaling in leukemic stem cells for maintenance of MLL leukemogenesis. Blood 2014; 124(22): 3284-94.
[http://dx.doi.org/10.1182/blood-2013-10-532523] [PMID: 25293777]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy