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Published in: Cancer Cell International 1/2020

01-12-2020 | osteosarcoma | Primary research

Expression profile analysis identifies key genes as prognostic markers for metastasis of osteosarcoma

Authors: Xiaoqing Guan, Zhiyuan Guan, Chunli Song

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

OS is the most common malignant tumor of bone which was featured with osteoid or immature bone produced by the malignant cells, and biomarkers are urgently needed to identify patients with this aggressive disease.

Methods

We downloaded gene expression profiles from GEO and TARGET datasets for OS, respectively, and performed WGCNA to identify the key module. Whereafter, functional annotation and GSEA demonstrated the relationships between target genes and OS.

Results

In this study, we discovered four key genes—ALOX5AP, HLA-DMB, HLA-DRA and SPINT2 as new prognostic markers and confirmed their relationship with OS metastasis in the validation set.

Conclusions

In conclusion, ALOX5AP, HLA-DMB, HLA-DRA and SPINT2 were identified by bioinformatics analysis as possible prognostic markers for OS metastasis.
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Literature
1.
go back to reference Arndt V, et al. Up-to-date monitoring of childhood cancer long-term survival in Europe: tumours of the sympathetic nervous system, retinoblastoma, renal and bone tumours, and soft tissue sarcomas. Ann Oncol. 2007;18(10):1722–33.PubMedCrossRef Arndt V, et al. Up-to-date monitoring of childhood cancer long-term survival in Europe: tumours of the sympathetic nervous system, retinoblastoma, renal and bone tumours, and soft tissue sarcomas. Ann Oncol. 2007;18(10):1722–33.PubMedCrossRef
2.
go back to reference Collins M, et al. Benefits and adverse events in younger versus older patients receiving neoadjuvant chemotherapy for osteosarcoma: findings from a meta-analysis. J Clin Oncol. 2013;31(18):2303–12.PubMedCrossRef Collins M, et al. Benefits and adverse events in younger versus older patients receiving neoadjuvant chemotherapy for osteosarcoma: findings from a meta-analysis. J Clin Oncol. 2013;31(18):2303–12.PubMedCrossRef
3.
go back to reference Mirabello L, Troisi RJ, Savage SA. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer. 2009;125(1):229–34.PubMedPubMedCentralCrossRef Mirabello L, Troisi RJ, Savage SA. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer. 2009;125(1):229–34.PubMedPubMedCentralCrossRef
4.
5.
go back to reference Bousquet M, et al. Whole-exome sequencing in osteosarcoma reveals important heterogeneity of genetic alterations. Ann Oncol. 2016;27(4):738–44.PubMedCrossRef Bousquet M, et al. Whole-exome sequencing in osteosarcoma reveals important heterogeneity of genetic alterations. Ann Oncol. 2016;27(4):738–44.PubMedCrossRef
6.
go back to reference Subbiah V, et al. Alpha particle radium 223 dichloride in high-risk osteosarcoma: a phase I dose escalation trial. Clin Cancer Res. 2019;25(13):3802–10.PubMedCrossRefPubMedCentral Subbiah V, et al. Alpha particle radium 223 dichloride in high-risk osteosarcoma: a phase I dose escalation trial. Clin Cancer Res. 2019;25(13):3802–10.PubMedCrossRefPubMedCentral
7.
go back to reference Cortini M, Avnet S, Baldini N. Mesenchymal stroma: role in osteosarcoma progression. Cancer Lett. 2017;405:90–9.PubMedCrossRef Cortini M, Avnet S, Baldini N. Mesenchymal stroma: role in osteosarcoma progression. Cancer Lett. 2017;405:90–9.PubMedCrossRef
8.
go back to reference Scott MC, et al. Comparative transcriptome analysis quantifies immune cell transcript levels, metastatic progression, and survival in osteosarcoma. Cancer Res. 2018;78(2):326–37.PubMedCrossRef Scott MC, et al. Comparative transcriptome analysis quantifies immune cell transcript levels, metastatic progression, and survival in osteosarcoma. Cancer Res. 2018;78(2):326–37.PubMedCrossRef
10.
12.
go back to reference Langfelder P, Horvath S. Fast R functions for robust correlations and hierarchical clustering. J Stat Softw. 2012;46(11):17.CrossRef Langfelder P, Horvath S. Fast R functions for robust correlations and hierarchical clustering. J Stat Softw. 2012;46(11):17.CrossRef
13.
go back to reference Gene Ontology Consortium. The gene ontology resource: 20 years and still going strong. Nucleic Acids Res. 2019;47(D1):D330–d338.CrossRef Gene Ontology Consortium. The gene ontology resource: 20 years and still going strong. Nucleic Acids Res. 2019;47(D1):D330–d338.CrossRef
15.
go back to reference Mootha VK, et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267–73.PubMedCrossRef Mootha VK, et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267–73.PubMedCrossRef
16.
go back to reference Subramanian A, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. 2005;102(43):15545–50. Subramanian A, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. 2005;102(43):15545–50.
18.
19.
go back to reference Whelan JS, Davis LE. Osteosarcoma, chondrosarcoma, and chordoma. J Clin Oncol. 2018;36(2):188–93.PubMedCrossRef Whelan JS, Davis LE. Osteosarcoma, chondrosarcoma, and chordoma. J Clin Oncol. 2018;36(2):188–93.PubMedCrossRef
20.
go back to reference Bielack S, et al. Osteosarcoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20(Suppl 4):137–9.PubMedCrossRef Bielack S, et al. Osteosarcoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20(Suppl 4):137–9.PubMedCrossRef
21.
go back to reference Smeland S, et al. Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. Eur J Cancer. 2019;109:36–50.PubMedPubMedCentralCrossRef Smeland S, et al. Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. Eur J Cancer. 2019;109:36–50.PubMedPubMedCentralCrossRef
22.
go back to reference Wunder JS, et al. Opportunities for improving the therapeutic ratio for patients with sarcoma. Lancet Oncol. 2007;8(6):513–24.PubMedCrossRef Wunder JS, et al. Opportunities for improving the therapeutic ratio for patients with sarcoma. Lancet Oncol. 2007;8(6):513–24.PubMedCrossRef
23.
go back to reference Piperno-Neumann S, et al. Zoledronate in combination with chemotherapy and surgery to treat osteosarcoma (OS2006): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2016;17(8):1070–80.PubMedCrossRef Piperno-Neumann S, et al. Zoledronate in combination with chemotherapy and surgery to treat osteosarcoma (OS2006): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2016;17(8):1070–80.PubMedCrossRef
25.
go back to reference Kohrman AQ, Matus DQ. Divide or conquer: cell cycle regulation of invasive behavior. Trends Cell Biol. 2017;27(1):12–25.PubMedCrossRef Kohrman AQ, Matus DQ. Divide or conquer: cell cycle regulation of invasive behavior. Trends Cell Biol. 2017;27(1):12–25.PubMedCrossRef
26.
go back to reference Gonzalez H, Hagerling C, Werb Z. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev. 2018;32(19–20):1267–84.PubMedPubMedCentralCrossRef Gonzalez H, Hagerling C, Werb Z. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev. 2018;32(19–20):1267–84.PubMedPubMedCentralCrossRef
28.
go back to reference Wu B, et al. The arachidonic acid metabolism protein-protein interaction network and its expression pattern in esophageal diseases. Am J Transl Res. 2018;10(3):907–24.PubMedPubMedCentral Wu B, et al. The arachidonic acid metabolism protein-protein interaction network and its expression pattern in esophageal diseases. Am J Transl Res. 2018;10(3):907–24.PubMedPubMedCentral
29.
go back to reference Shi Q, et al. Integrative analysis identifies DNMTs against immune-infiltrating neutrophils and dendritic cells in colorectal cancer. Epigenetics. 2019;14(4):392–404.PubMedPubMedCentralCrossRef Shi Q, et al. Integrative analysis identifies DNMTs against immune-infiltrating neutrophils and dendritic cells in colorectal cancer. Epigenetics. 2019;14(4):392–404.PubMedPubMedCentralCrossRef
31.
go back to reference Abelin JG, et al. Defining HLA-II ligand processing and binding rules with mass spectrometry enhances cancer epitope prediction. Immunity. 2019;51(4):766–779.e17.PubMedCrossRef Abelin JG, et al. Defining HLA-II ligand processing and binding rules with mass spectrometry enhances cancer epitope prediction. Immunity. 2019;51(4):766–779.e17.PubMedCrossRef
32.
go back to reference Aissani B, et al. SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi’s sarcoma. Genes Immun. 2014;15(6):424–9.PubMedPubMedCentralCrossRef Aissani B, et al. SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi’s sarcoma. Genes Immun. 2014;15(6):424–9.PubMedPubMedCentralCrossRef
33.
go back to reference Sun Z, et al. Major histocompatibility complex class II HLA-DRalpha is downregulated by Kaposi’s sarcoma-associated herpesvirus-encoded lytic transactivator RTA and MARCH8. J Virol. 2016;90(18):8047–58.PubMedPubMedCentralCrossRef Sun Z, et al. Major histocompatibility complex class II HLA-DRalpha is downregulated by Kaposi’s sarcoma-associated herpesvirus-encoded lytic transactivator RTA and MARCH8. J Virol. 2016;90(18):8047–58.PubMedPubMedCentralCrossRef
34.
35.
go back to reference Callahan MJ, et al. Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer. Clin Cancer Res. 2008;14(23):7667–73.PubMedPubMedCentralCrossRef Callahan MJ, et al. Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer. Clin Cancer Res. 2008;14(23):7667–73.PubMedPubMedCentralCrossRef
36.
go back to reference Brown PJ, et al. FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas. Leukemia. 2016;30(3):605–16.PubMedCrossRef Brown PJ, et al. FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas. Leukemia. 2016;30(3):605–16.PubMedCrossRef
37.
go back to reference Kongkham PN, et al. An epigenetic genome-wide screen identifies SPINT2 as a novel tumor suppressor gene in pediatric medulloblastoma. Cancer Res. 2008;68(23):9945–53.PubMedCrossRef Kongkham PN, et al. An epigenetic genome-wide screen identifies SPINT2 as a novel tumor suppressor gene in pediatric medulloblastoma. Cancer Res. 2008;68(23):9945–53.PubMedCrossRef
38.
go back to reference Roversi FM, Olalla Saad ST, Machado-Neto JA. Serine peptidase inhibitor Kunitz type 2 (SPINT2) in cancer development and progression. Biomed Pharmacother. 2018;101:278–86.PubMedCrossRef Roversi FM, Olalla Saad ST, Machado-Neto JA. Serine peptidase inhibitor Kunitz type 2 (SPINT2) in cancer development and progression. Biomed Pharmacother. 2018;101:278–86.PubMedCrossRef
Metadata
Title
Expression profile analysis identifies key genes as prognostic markers for metastasis of osteosarcoma
Authors
Xiaoqing Guan
Zhiyuan Guan
Chunli Song
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01179-x

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