Investigation of prognostic values of immune infiltration and LGMN expression in the microenvironment of osteosarcoma

被引:0
作者
Xu, Hualiang [1 ,2 ]
Xu, Dawei [1 ]
Zheng, Yinfeng [1 ]
Wang, Huajun [2 ]
Li, Aiguo [1 ]
Zheng, Xiaofei [2 ]
机构
[1] Jinan Univ, Guangzhou Red Cross Hosp, Dept Orthoped, 396 Tongfu Middle Rd, Guangzhou, Guangdong, Peoples R China
[2] Jinan Univ, Affiliated Hosp 1, Guangdong Prov Key Lab Speed Capabil, Dept Sports Med,Guangzhou Key Lab Precis Orthoped, 613 Huangpu Ave West, Guangzhou, Guangdong, Peoples R China
关键词
Osteosarcoma; LGMN; Immune infiltration; Bioinformatics; Prognosis; Therapeutic target; Consensus clustering analysis; TUMOR-ASSOCIATED MACROPHAGES; LEGUMAIN; CANCER; CHEMOTHERAPY; GROWTH; CELLS; METASTASIS; MIGRATION; SARCOMA; TRIAL;
D O I
10.1007/s12672-024-01123-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundOsteosarcoma (OS), the most common primary malignant bone tumor, predominantly affects children and young adults and is characterized by high invasiveness and poor prognosis. Despite therapeutic advancements, the survival rate remains suboptimal, indicating an urgent need for novel biomarkers and therapeutic targets. This study aimed to investigate the prognostic significance of LGMN expression and immune cell infiltration in the tumor microenvironment of OS.MethodsWe performed an integrative bioinformatics analysis utilizing the GEO and TARGET-OS databases to identify differentially expressed genes (DEGs) associated with LGMN in OS. We conducted Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to explore the biological pathways and functions. Additionally, we constructed protein-protein interaction (PPI) networks, a competing endogenous RNA (ceRNA) network, and applied the CIBERSORT algorithm to quantify immune cell infiltration. The diagnostic and prognostic values of LGMN were evaluated using the area under the receiver operating characteristic (ROC) curve and Cox regression analysis. Furthermore, we employed Consensus Clustering Analysis to explore the heterogeneity within OS samples based on LGMN expression.ResultsThe analysis revealed significant upregulation of LGMN in OS tissues. DEGs were enriched in immune response and antigen processing pathways, suggesting LGMN's role in immune modulation within the TME. The PPI and ceRNA network analyses provided insights into the regulatory mechanisms involving LGMN. Immune cell infiltration analysis indicated a correlation between high LGMN expression and increased abundance of M2 macrophages, implicating an immunosuppressive role. The diagnostic AUC for LGMN was 0.799, demonstrating its potential as a diagnostic biomarker. High LGMN expression correlated with reduced overall survival (OS) and progression-free survival (PFS). Importantly, Consensus Clustering Analysis identified two distinct subtypes of OS, highlighting the heterogeneity and potential for personalized medicine approaches.ConclusionsOur study underscores the prognostic value of LGMN in osteosarcoma and its potential as a therapeutic target. The identification of LGMN-associated immune cell subsets and the discovery of distinct OS subtypes through Consensus Clustering Analysis provide new avenues for understanding the immunosuppressive TME of OS and may aid in the development of personalized treatment strategies. Further validation in larger cohorts is warranted to confirm these findings.
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页数:22
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共 56 条
  • [1] Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis
    Antonia, Scott J.
    Borghaei, Hossein
    Ramalingam, Suresh S.
    Horn, Leora
    De Castro Carpeno, Javier
    Pluzanski, Adam
    Burgio, Marco A.
    Garassino, Marina
    Chow, Laura Q. M.
    Gettinger, Scott
    Crino, Lucio
    Planchard, David
    Butts, Charles
    Drilon, Alexander
    Wojcik-Tomaszewska, Joanna
    Otterson, Gregory A.
    Agrawal, Shruti
    Li, Ang
    Penrod, John R.
    Brahmer, Julie
    [J]. LANCET ONCOLOGY, 2019, 20 (10) : 1395 - 1408
  • [2] Families and clans of cysteine peptidases
    Barrett, AJ
    Rawlings, ND
    [J]. PERSPECTIVES IN DRUG DISCOVERY AND DESIGN, 1996, 6 : 1 - 11
  • [3] Future directions in the treatment of osteosarcoma
    Bishop, Michael W.
    Janeway, Katherine A.
    Gorlick, Richard
    [J]. CURRENT OPINION IN PEDIATRICS, 2016, 28 (01) : 26 - 33
  • [4] NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control
    Boettcher, Jan P.
    Bonavita, Eduardo
    Chakravarty, Probir
    Blees, Hanna
    Cabeza-Cabrerizo, Mar
    Sammicheli, Stefano
    Rogers, Neil C.
    Sahai, Erik
    Zelenay, Santiago
    Reis e Sousa, Caetano
    [J]. CELL, 2018, 172 (05) : 1022 - +
  • [5] Chen BB, 2018, METHODS MOL BIOL, V1711, P243, DOI 10.1007/978-1-4939-7493-1_12
  • [6] Integrated Analysis of Long Non-Coding RNA and mRNA Expression Profile in Pancreatic Cancer Derived Exosomes Treated Dendritic Cells by Microarray Analysis
    Chen, Jionghuang
    Wang, Shaowen
    Jia, Shengnan
    Ding, Guoping
    Jiang, Guixing
    Cao, Liping
    [J]. JOURNAL OF CANCER, 2018, 9 (01): : 21 - 31
  • [7] Cloning, isolation, and characterization of mammalian legumain, an asparaginyl endopeptidase
    Chen, JM
    Dando, PM
    Rawlings, ND
    Brown, MA
    Young, NE
    Stevens, RA
    Hewitt, E
    Watts, C
    Barrett, AJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (12) : 8090 - 8098
  • [8] USP17 Suppresses Tumorigenesis and Tumor Growth through Deubiquitinating AEP
    Chen, Xi
    Wang, Chen
    Liao, Keman
    Zhou, Sunhai
    Cao, Lu
    Chen, Jiayi
    Xu, Cheng
    Lin, Yingying
    [J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2019, 15 (04): : 738 - 748
  • [9] TIMs, TAMs, and PS- antibody targeting: implications for cancer immunotherapy
    Dayoub, Adam S.
    Brekken, Rolf A.
    [J]. CELL COMMUNICATION AND SIGNALING, 2020, 18 (01)
  • [10] Asparaginyl Endopeptidase (Legumain) Supports Human Th1 Induction via Cathepsin L-Mediated Intracellular C3 Activation
    Freeley, Simon
    Cardone, John
    Guenther, Sira C.
    West, Erin E.
    Reinheckel, Thomas
    Watts, Colin
    Kemper, Claudia
    Kolev, Martin, V
    [J]. FRONTIERS IN IMMUNOLOGY, 2018, 9