Abstract
Little progress has been made in the treatment and prognosis of osteosarcoma in the past 40 years. Tumor microenvironment (TME) plays a critical role in the progression of osteosarcoma. This study aims to determine immune-associated prognostic biomarkers for osteosarcoma patients. With the help of analytical tools including ESTIMATE, differential gene expression, LASSO, and univariate cox and multivariate cox regression analysis, osteosarcoma gene expression data from Gene Expression Omnibus (GEO) databases were investigated. Following the establishment of a prognostic risk score model, internal and external validations using the GEO and TARGET databases were carried out. A total of 44 and 55 samples respectively in the GSE21257 and the TARGET databases were included. Our analysis found 93 differentially expressed genes (DEGs) between the high and low-ImmuneScore groups. Through univariate cox and LASSO analysis, ALOX5AP was identified as an indicator of TME in osteosarcomas. ALOX5AP was then used to construct a prognostic risk model. Internal and external verification revealed that higher expression of ALOX5AP was correlated with lower risk. Through the CIBERSORT algorithm, the level of CD8 T cells was found to negatively correlate with the risk score. This study revealed that ALOX5AP is an indicator for predicting high CD8 lymphocyte infiltration and “hot” tumor microenvironment in osteosarcomas. Thus, ALOX5AP has the potential to act as a biomarker for effective immunotherapies in osteosarcoma patients.
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Data Availability
The data used to support the findings of this study are included within the article. All code used in this study is accessible when request.
Abbreviations
- ALOX5AP :
-
Arachidonate 5-lipoxygenase activating protein
- TME:
-
Tumor microenvironment
- GEO:
-
Gene expression omnibus
- DEGs:
-
Differentially expressed genes
- AUC:
-
Area under the curve
- TCR:
-
T cell receptor
- HLA:
-
Human leukocyte antigen
- FDR:
-
False discovery rate
- LASSO:
-
Least absolute shrinkage and selection operator
- TIC:
-
Tumor infiltrating immune cell
- KM:
-
Kaplan–Meier
- GO:
-
Gene ontology
- MHC:
-
Major histocompatibility complex
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
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Conceptualization, QH; Data acquisition and analysis, YC; Study design, YC and QH; Methodology, YC, CZ and XZ; Software, YC, CZ and XZ; Writing—original draft, Yongjun Chen; Writing—review & editing, Qiang Hua. All authors have read and and approved the final manuscript.
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Chen, Y., Zeng, C., Zhang, X. et al. ALOX5AP is an Indicator for High CD8 Lymphocyte Infiltration and “Hot” Tumor Microenvironment in Osteosarcoma: A Bioinformatic Study. Biochem Genet 61, 2363–2381 (2023). https://doi.org/10.1007/s10528-023-10374-0
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DOI: https://doi.org/10.1007/s10528-023-10374-0