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The role of m6A-related lncRNAs on prognosis and chemoradiothrapy response of osteosarcoma: potential molecular pathways
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Y. Zhou   , Y. Bi , M. Wan , N. Xu , Y. Xu , P. Liu , H. Jiang , H. Fang , H. Hu , S. Xu , S. Lan |
| Department of Orthopaedics, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai 200235, China , xusuyang |
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Abstract: (162 Views) |
Background: Conventional treatments on osteosarcoma (OS) yield limited improvements in metastatic or relapsed cases, necessitating innovative therapeutic strategies. This study's objective is to reveal the role of long non-coding RNAs (lncRNAs) in prognosis and potential molecular pathways of OS. Materials and Methods: This study integrated bioinformatics, statistical analysis, and computational techniques to investigate m6A-related prognostic lncRNA clusters in OS. Consensus clustering and risk analysis were performed on the m6A-related prognostic lncRNAs. Nomogram model was built for survival prediction, and was assessed using survival time receiver operator characteristic (ROC) analysis and decision curves. A competitive endogenous RNA (ceRNA) network was built to explore lncRNA-miRNA (microRNA)-mRNA interactions using the microRNA database and metascape website, followed by functional enrichment analyses. Results: The analysis unveiled three distinct OS clusters, with Cluster 2 exhibiting the highest risk in the immune microenvironment. High risk 7-lncRNA signature demonstrated strong prognostic value in predicting OS overall survival. The ceRNA network highlighted complex interactions among mRNAs, miRNAs and lncRNAs. Functional enrichment analysis indicated that mRNAs within the ceRNA network were linked to many biological functions. Furthermore, 30 differentially expressed genes (DEGs) derived from low-risk and high-risk groups enriched in GO-BP connected to MAGE (melanoma antigen gene) family member A2 (MAGEA2) and MAGEA2B. These DEGs in high risk group were also upregulated in the three KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway. Conclusion: This study disclosed the role of high-risk m6A-associated lncRNAs in prognosis and potential molecular pathways of OS. These findings provided novel insights into OS pathogenesis and potential therapeutic targets, warranting further validation in clinical settings. |
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| Keywords: osteosarcoma, long non-coding RNA (lncRNA), m6A modification, prognosis, chemoradiotherapy response, ceRNA network. |
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Full-Text [PDF 2398 kb]
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Type of Study: Original Research |
Subject:
Radiation Biology
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1. 1. Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer Statistics, 2021. CA: A Cancer Journal for Clinicians. 71(1): 7-33. [ DOI:10.3322/caac.21654] 2. Harrison DJ and Schwartz CL (2017) Osteogenic sarcoma: Systemic chemotherapy options for localized disease. Current Treatment Options in Oncology, 18(4): 24. [ DOI:10.1007/s11864-017-0464-2] 3. Jafari F, Javdansirat S, Sanaie S, et al. (2020) Osteosarcoma: A comprehensive review of management and treatment strategies. Annals of Diagnostic Pathology, 49: 151654. [ DOI:10.1016/j.anndiagpath.2020.151654] 4. Liu J, Lian T, Chen H, et al. (2021) Pretreatment prediction of relapse risk in patients with osteosarcoma using radiomics nomogram based on CT: A retrospective multicenter study. BioMed Research International, 2021: 6674471. [ DOI:10.1155/2021/6674471] 5. Ferguson JL and Turner SP (2018) Bone Cancer: Diagnosis and treatment principles. American Family Physician, 98(4): 205-13. 6. Chen C, Xie L, Ren T, et al. ( 2021) Immunotherapy for osteosarcoma: Fundamental mechanism, rationale, and recent breakthroughs. Cancer letters, 500: 1-10. [ DOI:10.1016/j.canlet.2020.12.024] 7. Harrison DJ, Geller DS, Gill JD, et al. (2018) Current and future therapeutic approaches for osteosarcoma. Expert Review of Anticancer Therapy, 18(1): 39-50. [ DOI:10.1080/14737140.2018.1413939] 8. Tsukamoto S, Errani C, Angelini A, Mavrogenis AF (2020) Current treatment considerations for osteosarcoma metastatic at presentation. Orthopedics, 43(5): e345-e58. [ DOI:10.3928/01477447-20200721-05] 9. Chen W, Liu S, Wang F (2021) Potential impact and mechanism of long non-coding RNAs on cancer and associated T cells. Journal of Cancer, 12(16): 4873-82. [ DOI:10.7150/jca.58859] 10. Guo R, Zou B, Liang Y, et al. (2021) LncRNA RCAT1 promotes tumor progression and metastasis via miR-214-5p/E2F2 axis in renal cell carcinoma. Cell Death & Disease, 12(7): 689. [ DOI:10.1038/s41419-021-03955-7] 11. Che D, Fang Z, Mai H, et al. (2021) The lncRNA ANRIL gene rs2151280 GG genotype is associated with increased susceptibility to recurrent miscarriage in a Southern Chinese population. J Inflammation Research, 14: 2865-72. [ DOI:10.2147/JIR.S304801] 12. Liu X, Yin Z, Xu L, et al. (2021) Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway. Cell Death & Disease, 12(2): 173. [ DOI:10.1038/s41419-021-03435-y] 13. Hou T, Ye L, Wu S (2021) Knockdown of LINC00504 Inhibits the Proliferation and Invasion of Breast Cancer via the Downregulation of miR-140-5p. OncoTargets and Therapy, 14: 3991-4003. [ DOI:10.2147/OTT.S294965] 14. Chen K, Zhang Z, Yu A, et al. (2020) lncRNA DLGAP1-AS2 knockdown inhibits hepatocellular carcinoma cell migration and invasion by regulating miR-154-5p methylation. BioMed Research International, 2020: 6575724. [ DOI:10.1155/2020/6575724] 15. Huang Q, Lin Y, Chen C, et al. (2021) Immune-related LncRNAs affect the prognosis of osteosarcoma, which are related to the tumor immune microenvironment. Frontiers in Cell and Developmental Biology, 9: 731311. [ DOI:10.3389/fcell.2021.731311] 16. Yang M, Zheng H, Xu K, et al. (2022) A novel signature to guide osteosarcoma prognosis and immune microenvironment: Cuproptosis-related lncRNA. Frontiers in Immunology, 13: 919231. [ DOI:10.3389/fimmu.2022.919231] 17. Zhang J, Huang C, Zhu G, et al. (2022) Selection of lncRNAs that influence the prognosis of osteosarcoma based on copy number variation data. Journal of Oncology, 2022: 8024979. [ DOI:10.1155/2022/8024979] 18. Fu R and Hong X (2022) Discovery of new therapeutic targets for osteosarcoma treatment based on immune-related lncRNAs in the tumor microenvironment. BioMed Res Int, 2022: 3113857. [ DOI:10.1155/2022/3113857] 19. Xie H, Shi M, Liu Y, et al. (2022) Identification of m6A- and ferroptosis-related lncRNA signature for predicting immune efficacy in hepatocellular carcinoma. Frontiers in Immunology, 13: 914977. [ DOI:10.3389/fimmu.2022.914977] 20. Feng ZH, Liang YP, Cen JJ, et al. (2022) m6A-immune-related lncRNA prognostic signature for predicting immune landscape and prognosis of bladder cancer. J Translational Medicine, 20(1): 492. [ DOI:10.1186/s12967-022-03711-1] 21. Hou P, Meng S, Li M, et al. (2021) LINC00460/DHX9/IGF2BP2 complex promotes colorectal cancer proliferation and metastasis by mediating HMGA1 mRNA stability depending on m6A modification. J Experimental & Clinical Cancer Research, 40(1): 52. [ DOI:10.1186/s13046-021-01857-2] 22. Lang C, Yin C, Lin K, et al. (2021) A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2-mediated IGF1R mRNA stabilization. Clinical and Translational Medicine, 11(6): e426. [ DOI:10.1002/ctm2.426] 23. Bi Y, Meng D, Wan M, et al. (2022) m6A-related lncRNAs predict overall survival of patients and regulate the tumor immune microenvironment in osteosarcoma. Computational Intelligence and Neuroscience, 2022: 9315283. [ DOI:10.1155/2022/9315283] 24. Pan J, Huang Z, Xu Y (2021) m5C-related lncRNAs predict overall survival of patients and regulate the tumor immune microenvironment in lung adenocarcinoma. Frontiers in Cell and Developmental Biology, 9: 671821. [ DOI:10.3389/fcell.2021.671821] 25. Hayase E and Jenq RR (2021) Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer. Genome Medicine, 13(1): 107. [ DOI:10.1186/s13073-021-00923-w] 26. Price G, Bouras A, Hambardzumyan D, Hadjipanayis CG (2021) Current knowledge on the immune microenvironment and emerging immunotherapies in diffuse midline glioma. EBioMedicine. 2021;69:103453. [ DOI:10.1016/j.ebiom.2021.103453] 27. Zhang K, Ping L, Du T, et al. (2021) A ferroptosis-related lncRNAs signature predicts prognosis and immune microenvironment for breast cancer. Frontiers in Molecular Biosciences, 8: 678877. [ DOI:10.3389/fmolb.2021.678877] |
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Zhou Y, Bi Y, Wan M, Xu N, Xu Y, Liu P, et al . The role of m6A-related lncRNAs on prognosis and chemoradiothrapy response of osteosarcoma: potential molecular pathways. Int J Radiat Res 2024; 22 (2) :457-465 URL: http://ijrr.com/article-1-5469-en.html
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