Skip to main content
Top
Published in: BMC Musculoskeletal Disorders 1/2024

Open Access 01-12-2024 | Osteosarcoma | Research

Identification of allograft inflammatory factor-1 suppressing the progression and indicating good prognosis of osteosarcoma

Authors: Wenda Liu, Tao Shi, Di Zheng, Guangshui Ke, Jingteng Chen

Published in: BMC Musculoskeletal Disorders | Issue 1/2024

Login to get access

Abstract

Background

Osteosarcoma is one of the most common cancers worldwide. Intense efforts have been made to elucidate the pathogeny, but the mechanisms of osteosarcoma are still not well understood. We aimed to investigate the potential biomarker, allograft inflammatory factor-1 (AIF1), affecting the progression and prognosis of osteosarcoma.

Methods

Three microarray datasets were downloaded from GEO datasets and one was obtained from the TCGA dataset. The differentially expressed genes (DEGs) were identified. GO and KEGG functional enrichment analyses of overlapped DEGs were performed. The PPI network of overlapped DEGs was constructed by STRING and visualized with Cytoscape. Overall survival (OS) and Metastasis free survival (MFS) were analyzed from GSE21257. Finally, the effect of the most relevant core gene affecting the progression of osteosarcoma was examined in vitro.

Results

One hundred twenty six DEGs were identified, consisting of 65 upregulated and 61 downregulated genes. Only AIF1 was significantly associated with OS and MFS. It was found that AIF1 could be enriched into the NF-κB signaling pathway. GSEA and ssGSEA analyses showed that AIF1 was associated with the immune invasion of tumors. Cell experiments showed that AIF1 was underexpressed in osteosarcoma cell lines, while the malignant propriety was attenuated after overexpressing the expression of AIF1. Moreover, AIF1 also affects the expression of the NF-κB pathway.

Conclusion

In conclusion, DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the carcinogenesis and progression of osteosarcoma, and provide candidate targets for diagnosis and treatment of osteosarcoma.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jiang ZY, Liu JB, Wang XF, Ma YS, Fu D. Current status and prospects of clinical treatment of osteosarcoma. Technol Cancer Res Treat. 2022;21:15330338221124696.CrossRefPubMedPubMedCentral Jiang ZY, Liu JB, Wang XF, Ma YS, Fu D. Current status and prospects of clinical treatment of osteosarcoma. Technol Cancer Res Treat. 2022;21:15330338221124696.CrossRefPubMedPubMedCentral
2.
go back to reference Simpson S, Dunning MD, de Brot S, Grau-Roma L, Mongan NP, Rutland CS. Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics. Acta Vet Scand. 2017;59:71.CrossRefPubMedPubMedCentral Simpson S, Dunning MD, de Brot S, Grau-Roma L, Mongan NP, Rutland CS. Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics. Acta Vet Scand. 2017;59:71.CrossRefPubMedPubMedCentral
3.
go back to reference Szewczyk M, Lechowski R, Zabielska K. What do we know about canine osteosarcoma treatment? Review Vet Res Commun. 2015;39:61–7.CrossRefPubMed Szewczyk M, Lechowski R, Zabielska K. What do we know about canine osteosarcoma treatment? Review Vet Res Commun. 2015;39:61–7.CrossRefPubMed
5.
go back to reference Sikora M, Kopec B, Piotrowska K, Pawlik A. Role of allograft inflammatory factor-1 in pathogenesis of diseases. Immunol Lett. 2020;218:1–4.CrossRefPubMed Sikora M, Kopec B, Piotrowska K, Pawlik A. Role of allograft inflammatory factor-1 in pathogenesis of diseases. Immunol Lett. 2020;218:1–4.CrossRefPubMed
6.
go back to reference Baranzini N, Monti L, Vanotti M, Orlandi VT, Bolognese F, Scaldaferri D, Girardello R, Tettamanti G, de Eguileor M, Vizioli J, Taramelli R, Acquati F, Grimaldi A. AIF-1 and RNASET2 play complementary roles in the innate immune response of medicinal leech. J Innate Immun. 2019;11:150–67.CrossRefPubMed Baranzini N, Monti L, Vanotti M, Orlandi VT, Bolognese F, Scaldaferri D, Girardello R, Tettamanti G, de Eguileor M, Vizioli J, Taramelli R, Acquati F, Grimaldi A. AIF-1 and RNASET2 play complementary roles in the innate immune response of medicinal leech. J Innate Immun. 2019;11:150–67.CrossRefPubMed
7.
8.
go back to reference Egana-Gorrono L, Chinnasamy P, Casimiro I, Almonte VM, Parikh D, Oliveira-Paula GH, Jayakumar S, Law C, Riascos-Bernal DF, Sibinga NES. Allograft inflammatory factor-1 supports macrophage survival and efferocytosis and limits necrosis in atherosclerotic plaques. Atherosclerosis. 2019;289:184–94.CrossRefPubMedPubMedCentral Egana-Gorrono L, Chinnasamy P, Casimiro I, Almonte VM, Parikh D, Oliveira-Paula GH, Jayakumar S, Law C, Riascos-Bernal DF, Sibinga NES. Allograft inflammatory factor-1 supports macrophage survival and efferocytosis and limits necrosis in atherosclerotic plaques. Atherosclerosis. 2019;289:184–94.CrossRefPubMedPubMedCentral
9.
go back to reference Nagahara H, Seno T, Yamamoto A, Obayashi H, Inoue T, Kida T, Nakabayashi A, Kukida Y, Fujioka K, Fujii W, Murakami K, Kohno M, Kawahito Y. Role of allograft inflammatory factor-1 in bleomycin-induced lung fibrosis. Biochem Biophys Res Commun. 2018;495:1901–7.CrossRefPubMed Nagahara H, Seno T, Yamamoto A, Obayashi H, Inoue T, Kida T, Nakabayashi A, Kukida Y, Fujioka K, Fujii W, Murakami K, Kohno M, Kawahito Y. Role of allograft inflammatory factor-1 in bleomycin-induced lung fibrosis. Biochem Biophys Res Commun. 2018;495:1901–7.CrossRefPubMed
10.
go back to reference Ye Y, Miao S, Lu R, Xia X, Chen Y, Zhang J, Wu X, He S, Qiang F, Zhou J. Allograft inflammatory factor-1 is an independent prognostic indicator that regulates beta-catenin in gastric cancer. Oncol Rep. 2014;31:828–34.CrossRefPubMed Ye Y, Miao S, Lu R, Xia X, Chen Y, Zhang J, Wu X, He S, Qiang F, Zhou J. Allograft inflammatory factor-1 is an independent prognostic indicator that regulates beta-catenin in gastric cancer. Oncol Rep. 2014;31:828–34.CrossRefPubMed
11.
go back to reference Zhang Q, Sun S, Zhu C, Xie F, Cai Q, Sun H, Chen G, Liang X, Xie H, Shi J, Liao Y, Zhou J. Expression of allograft inflammatory Factor-1 (AIF-1) in hepatocellular carcinoma. Med Sci Monit. 2018;24:6218–28.CrossRefPubMedPubMedCentral Zhang Q, Sun S, Zhu C, Xie F, Cai Q, Sun H, Chen G, Liang X, Xie H, Shi J, Liao Y, Zhou J. Expression of allograft inflammatory Factor-1 (AIF-1) in hepatocellular carcinoma. Med Sci Monit. 2018;24:6218–28.CrossRefPubMedPubMedCentral
12.
go back to reference Ai XL, Yao F, Wang XJ, Duan DB, Li K, Hu ZY, Yin G, Wang M, Wu BY. Role of allograft inflammatory factor-1 in regulating the proliferation, migration and apoptosis of colorectal cancer cells. Nan Fang Yi Ke Da Xue Xue Bao. 2018;38:511–9.PubMed Ai XL, Yao F, Wang XJ, Duan DB, Li K, Hu ZY, Yin G, Wang M, Wu BY. Role of allograft inflammatory factor-1 in regulating the proliferation, migration and apoptosis of colorectal cancer cells. Nan Fang Yi Ke Da Xue Xue Bao. 2018;38:511–9.PubMed
13.
go back to reference Li B, Fang L, Wang B, Yang Z, Zhao T. Identification of prognostic RBPs in osteosarcoma. Technol Cancer Res Treat. 2021;20:15330338211004918.PubMedPubMedCentral Li B, Fang L, Wang B, Yang Z, Zhao T. Identification of prognostic RBPs in osteosarcoma. Technol Cancer Res Treat. 2021;20:15330338211004918.PubMedPubMedCentral
14.
go back to reference Fan H, Lu S, Wang S, Zhang S. Identification of critical genes associated with human osteosarcoma metastasis based on integrated gene expression profiling. Mol Med Rep. 2019;20:915–30.PubMedPubMedCentral Fan H, Lu S, Wang S, Zhang S. Identification of critical genes associated with human osteosarcoma metastasis based on integrated gene expression profiling. Mol Med Rep. 2019;20:915–30.PubMedPubMedCentral
15.
go back to reference Chen X, Zhang N, Zheng Y, Tong Z, Yang T, Kang X, He Y, Dong L. Identification of key genes and pathways in osteosarcoma by bioinformatics analysis. Comput Math Methods Med. 2022;2022:7549894.PubMedPubMedCentral Chen X, Zhang N, Zheng Y, Tong Z, Yang T, Kang X, He Y, Dong L. Identification of key genes and pathways in osteosarcoma by bioinformatics analysis. Comput Math Methods Med. 2022;2022:7549894.PubMedPubMedCentral
16.
go back to reference Xu F, Yan J, Peng Z, Liu J, Li Z. Comprehensive analysis of a glycolysis and cholesterol synthesis-related genes signature for predicting prognosis and immune landscape in osteosarcoma. Front Immunol. 2022;13:1096009.CrossRefPubMedPubMedCentral Xu F, Yan J, Peng Z, Liu J, Li Z. Comprehensive analysis of a glycolysis and cholesterol synthesis-related genes signature for predicting prognosis and immune landscape in osteosarcoma. Front Immunol. 2022;13:1096009.CrossRefPubMedPubMedCentral
17.
go back to reference Sherman BT, Hao M, Qiu J, Jiao X, Baseler MW, Lane HC, Imamichi T, Chang W. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022;50:W216–21.CrossRefPubMedPubMedCentral Sherman BT, Hao M, Qiu J, Jiao X, Baseler MW, Lane HC, Imamichi T, Chang W. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022;50:W216–21.CrossRefPubMedPubMedCentral
18.
go back to reference Zeng X, Shi G, He Q, Zhu P. Screening and predicted value of potential biomarkers for breast cancer using bioinformatics analysis. Sci Rep. 2021;11:20799.CrossRefPubMedPubMedCentral Zeng X, Shi G, He Q, Zhu P. Screening and predicted value of potential biomarkers for breast cancer using bioinformatics analysis. Sci Rep. 2021;11:20799.CrossRefPubMedPubMedCentral
19.
go back to reference Kanehisa M, Sato Y, Kawashima M. KEGG mapping tools for uncovering hidden features in biological data. Protein Sci. 2022;31:47–53.CrossRefPubMed Kanehisa M, Sato Y, Kawashima M. KEGG mapping tools for uncovering hidden features in biological data. Protein Sci. 2022;31:47–53.CrossRefPubMed
20.
go back to reference C. Gene Ontology, Aleksander SA, Balhoff J, Carbon S, Cherry JM, Drabkin HJ, et al. The Gene Ontology knowledgebase in 2023. Genetics. 2023;224. C. Gene Ontology, Aleksander SA, Balhoff J, Carbon S, Cherry JM, Drabkin HJ, et al. The Gene Ontology knowledgebase in 2023. Genetics. 2023;224.
21.
go back to reference Liu W, Xia K, Zheng D, Huang X, Wei Z, Wei Z, Guo W. Construction of a prognostic risk score model based on the ARHGAP family to predict the survival of osteosarcoma. BMC Cancer. 2023;23:1179.CrossRefPubMedPubMedCentral Liu W, Xia K, Zheng D, Huang X, Wei Z, Wei Z, Guo W. Construction of a prognostic risk score model based on the ARHGAP family to predict the survival of osteosarcoma. BMC Cancer. 2023;23:1179.CrossRefPubMedPubMedCentral
22.
go back to reference Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, et al. The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 49(2021):D605–12. Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, et al. The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 49(2021):D605–12.
23.
go back to reference Pinero J, Sauch J, Sanz F, Furlong LI. The DisGeNET cytoscape app: exploring and visualizing disease genomics data. Comput Struct Biotechnol J. 2021;19:2960–7.CrossRefPubMedPubMedCentral Pinero J, Sauch J, Sanz F, Furlong LI. The DisGeNET cytoscape app: exploring and visualizing disease genomics data. Comput Struct Biotechnol J. 2021;19:2960–7.CrossRefPubMedPubMedCentral
24.
go back to reference Guo S, Wu J, Zhou W, Liu X, Liu Y, Zhang J, Jia S, Li J, Wang H. Identification and analysis of key genes associated with acute myocardial infarction by integrated bioinformatics methods. Medicine (Baltimore). 2021;100:e25553.CrossRefPubMed Guo S, Wu J, Zhou W, Liu X, Liu Y, Zhang J, Jia S, Li J, Wang H. Identification and analysis of key genes associated with acute myocardial infarction by integrated bioinformatics methods. Medicine (Baltimore). 2021;100:e25553.CrossRefPubMed
25.
go back to reference Guo H, Zhang Z, Wang Y, Xue S. Identification of crucial genes and pathways associated with prostate cancer in multiple databases. J Int Med Res. 2021;49:3000605211016624.CrossRefPubMed Guo H, Zhang Z, Wang Y, Xue S. Identification of crucial genes and pathways associated with prostate cancer in multiple databases. J Int Med Res. 2021;49:3000605211016624.CrossRefPubMed
26.
go back to reference Mi N, Cao J, Zhang J, Fu W, Huang C, Gao L, Yue P, Bai B, Lin Y, Meng W, Li X. Identification of hub genes involved in the occurrence and development of hepatocellular carcinoma via bioinformatics analysis. Oncol Lett. 2020;20:1695–708.CrossRefPubMedPubMedCentral Mi N, Cao J, Zhang J, Fu W, Huang C, Gao L, Yue P, Bai B, Lin Y, Meng W, Li X. Identification of hub genes involved in the occurrence and development of hepatocellular carcinoma via bioinformatics analysis. Oncol Lett. 2020;20:1695–708.CrossRefPubMedPubMedCentral
28.
29.
go back to reference Chen C, Xie L, Ren T, Huang Y, Xu J, Guo W. Immunotherapy for osteosarcoma: fundamental mechanism, rationale, and recent breakthroughs. Cancer Lett. 2021;500:1–10.CrossRefPubMed Chen C, Xie L, Ren T, Huang Y, Xu J, Guo W. Immunotherapy for osteosarcoma: fundamental mechanism, rationale, and recent breakthroughs. Cancer Lett. 2021;500:1–10.CrossRefPubMed
30.
go back to reference Harrison DJ, Geller DS, Gill JD, Lewis VO, Gorlick R. Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther. 2018;18:39–50.CrossRefPubMed Harrison DJ, Geller DS, Gill JD, Lewis VO, Gorlick R. Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther. 2018;18:39–50.CrossRefPubMed
31.
go back to reference Sadykova LR, Ntekim AI, Muyangwa-Semenova M, Rutland CS, Jeyapalan JN, Blatt N, Rizvanov AA. Epidemiology and risk factors of osteosarcoma. Cancer Investig. 2020;38:259–69.CrossRef Sadykova LR, Ntekim AI, Muyangwa-Semenova M, Rutland CS, Jeyapalan JN, Blatt N, Rizvanov AA. Epidemiology and risk factors of osteosarcoma. Cancer Investig. 2020;38:259–69.CrossRef
32.
go back to reference Ibrahim B, McMahon DP, Hufsky F, Beer M, Deng L, Mercier PL, Palmarini M, Thiel V, Marz M. A new era of virus bioinformatics. Virus Res. 2018;251:86–90.CrossRefPubMed Ibrahim B, McMahon DP, Hufsky F, Beer M, Deng L, Mercier PL, Palmarini M, Thiel V, Marz M. A new era of virus bioinformatics. Virus Res. 2018;251:86–90.CrossRefPubMed
33.
go back to reference Li L, Lei Q, Zhang S, Kong L, Qin B. Screening and identification of key biomarkers in hepatocellular carcinoma: evidence from bioinformatic analysis. Oncol Rep. 2017;38:2607–18.CrossRefPubMedPubMedCentral Li L, Lei Q, Zhang S, Kong L, Qin B. Screening and identification of key biomarkers in hepatocellular carcinoma: evidence from bioinformatic analysis. Oncol Rep. 2017;38:2607–18.CrossRefPubMedPubMedCentral
34.
go back to reference Cheng Y, Wang K, Geng L, Sun J, Xu W, Liu D, Gong S, Zhu Y. Identification of candidate diagnostic and prognostic biomarkers for pancreatic carcinoma. EBioMedicine. 2019;40:382–93.CrossRefPubMedPubMedCentral Cheng Y, Wang K, Geng L, Sun J, Xu W, Liu D, Gong S, Zhu Y. Identification of candidate diagnostic and prognostic biomarkers for pancreatic carcinoma. EBioMedicine. 2019;40:382–93.CrossRefPubMedPubMedCentral
35.
go back to reference Wang JS, Duan MY, Zhong YS, Li XD, Du SX, Xie P, Zheng GZ, Han JM. Investigating ageinduced differentially expressed genes and potential molecular mechanisms in osteosarcoma based on integrated bioinformatics analysis. Mol Med Rep. 2019;19:2729–39.PubMedPubMedCentral Wang JS, Duan MY, Zhong YS, Li XD, Du SX, Xie P, Zheng GZ, Han JM. Investigating ageinduced differentially expressed genes and potential molecular mechanisms in osteosarcoma based on integrated bioinformatics analysis. Mol Med Rep. 2019;19:2729–39.PubMedPubMedCentral
36.
go back to reference Zoabi Y, Shomron N. Processing and analysis of RNA-seq data from public resources. Methods Mol Biol. 2021;2243:81–94.CrossRefPubMed Zoabi Y, Shomron N. Processing and analysis of RNA-seq data from public resources. Methods Mol Biol. 2021;2243:81–94.CrossRefPubMed
37.
go back to reference Davis PJ, Mousa SA, Schechter GP, Lin HY. Platelet ATP, thyroid hormone receptor on integrin alphavbeta3 and Cancer metastasis. Horm Cancer. 2020;11:13–6.CrossRefPubMed Davis PJ, Mousa SA, Schechter GP, Lin HY. Platelet ATP, thyroid hormone receptor on integrin alphavbeta3 and Cancer metastasis. Horm Cancer. 2020;11:13–6.CrossRefPubMed
40.
go back to reference Zagzag J, Hu MI, Fisher SB, Perrier ND. Hypercalcemia and cancer: differential diagnosis and treatment. CA Cancer J Clin. 2018;68:377–86.CrossRefPubMed Zagzag J, Hu MI, Fisher SB, Perrier ND. Hypercalcemia and cancer: differential diagnosis and treatment. CA Cancer J Clin. 2018;68:377–86.CrossRefPubMed
41.
go back to reference van Dam PA, Verhoeven Y, Trinh XB, Wouters A, Lardon F, Prenen H, Smits E, Baldewijns M, Lammens M. RANK/RANKL signaling inhibition may improve the effectiveness of checkpoint blockade in cancer treatment. Crit Rev Oncol Hematol. 2019;133:85–91.CrossRefPubMed van Dam PA, Verhoeven Y, Trinh XB, Wouters A, Lardon F, Prenen H, Smits E, Baldewijns M, Lammens M. RANK/RANKL signaling inhibition may improve the effectiveness of checkpoint blockade in cancer treatment. Crit Rev Oncol Hematol. 2019;133:85–91.CrossRefPubMed
Metadata
Title
Identification of allograft inflammatory factor-1 suppressing the progression and indicating good prognosis of osteosarcoma
Authors
Wenda Liu
Tao Shi
Di Zheng
Guangshui Ke
Jingteng Chen
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2024
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-024-07363-8

Other articles of this Issue 1/2024

BMC Musculoskeletal Disorders 1/2024 Go to the issue