Development and Validation of a Novel Immune-Related Prognostic Model and the Potential Mechanism in Metastatic Synovial Sarcoma

Background: Several clinical trials have shown that immunotherapy plays a pivotal role in the treatment of patients with metastatic synovial sarcoma. Immune-related genes (IRGs) have been demonstrated to play an important role in tumorigenesis and tumour microenvironment formation. However, the clinical significance of IRGs in patients with synovial sarcoma(SS) is still unclear, and systematic analysis is lacking. Methods: We downloaded the GSE40021 dataset from the GEO database, which included 30 cases of nonmetastatic and 28 cases of metastatic SS. Firstly,We combined the immune-related ImmPort gene set to search for SS related to metastatic and differentially expressed immune-related genes (DEIRGs). We then performed univariate Cox regression analysis from soft tissue sarcoma database in TCGA to identify DEIRGs that related to overall survival, and constructed an immune-related prognostic assessment model. We used the assessment model to evaluate the infiltration of immune cells  through the ssGSEA algorithm. Finally, we collected tumour tissues in our centre to verify the RNA expression levels by real-time quantitative reverse transcription(RT-qPCR) analysis. Findings: The study screened a total of six DEIRGs which were closely related to prognosisin in metastatic SS and constructed an immune-related prognostic assessment model which was an independent prognostic factor different from other clinical features. Further analysis showed that there was no significant difference in the expression of several immune checkpoints between the two groups in the GSE40021 data. Moreover, the GREM2 and CTSS genes were significantly expressed in metastatic patients. Further verification of SS tissues from our centre by RT-qPCR analysis demonstrated reduced infiltration of activated NK cells and macrophages but increased M2-type macrophages in metastatic patients. Interpretation: The study successfully constructed an immune-related prognostic assessment model and probably explain the poor efficacy PD-1 inhibitors for SS patients. Together,the research deepens our understanding of the tumor immune microenvironment and proposed a new immune mechanism of metastatic SS. Funding Information: This study was supported by the National Natural Science Foundation of China (91959115, 81872268,and 81702665), Natural Science Foundation of Guangdong Province (2019A1515011192) and the Fundamental Research Funds for the Central Universities (19ykpy189). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The studies involving human participants were reviewed and approved by the Medical Ethics Committee of the Sun Yat-sen University Cancer Center. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.