Comprehensive profiling of immune-related genes in soft tissue sarcoma patients
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Journal of Translational Medicine Open Access
RESEARCH
Comprehensive profiling of immune‑related genes in soft tissue sarcoma patients Chuan Hu1,2†, Bo Chen1,3†, Zhangheng Huang1†, Chuan Liu4, Lin Ye3, Cailin Wang3, Yuexin Tong1, Jiaxin Yang3 and Chengliang Zhao1*
Abstract Background: Immune-related genes (IRGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of IRGs and their clinical significance in soft tissue sarcoma (STS) patients is lacking. Methods: Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed immune-related genes (DEIRGs) were determined by matching the DEG and ImmPort gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEIRGs was conducted, and associations with prognosis, the tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for progression free survival (PFS), were established and validated in an independent set. Finally, two transcription factor (TF)-IRG regulatory networks were constructed, and a crucial regulatory axis was validated. Results: In total, 364 DEIRGs and four clusters were identified. OS, TME scores, five immune checkpoints, and 12 types of immune cells were found to be significantly different among the four clusters. The two prognostic signatures incorporating 20 DEIRGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.879 (95%CI 0.832 ~ 0.926) and 0.825 (95%CI 0.776 ~ 0.874) for the OS and PFS signatures, respectively. Finally, TF-IRG regulatory networks were established, and the MYH11-ADM regulatory axis was verified in three independent datasets. Conclusion: This comprehensive analysis of the IRG landscape in soft tissue sarcoma revealed novel IRGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy. Keywords: Immune-related genes, Soft tissue sarcoma, Immune cell, Immune checkpoint, Prognosis, Transcription factor
*Correspondence: [email protected] † Chuan Hu, Bo Chen and Zhangheng Huang contribute equally to this work 1 Department of Orthopedic, Affiliated Hospital of Chengde Medical University, Hebei, China Full list of author information is available at the end of the article
Background Soft tissue sarcomas (STSs) are a rare group of heterogeneous malignant tumors originating from mesenchymal tissue and comprise more than 50 histological subtypes [1, 2]. Although STSs only account for 1% of all malignancies, they account for approximately 10% of malignancies in
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