Integrative profiling analysis reveals prognostic significance, molecular characteristics, and tumor immunity of angiogenesis-related genes in soft tissue sarcoma

BackgroundSoft tissue sarcoma (STS) is a class of malignant tumors originating from mesenchymal stroma with a poor prognosis. Accumulating evidence has proved that angiogenesis is an essential hallmark of tumors. Nevertheless, there is a paucity of comprehensive research exploring the association of angiogenesis-related genes (ARGs) with STS. MethodsThe ARGs were extracted from previous literature, and the differentially expressed ARGs were screened for subsequent analysis. Next, the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were conducted to establish the angiogenesis-related signature (ARSig). The predictive performance of the novel ARSig was confirmed using internal and external validation, subgroup survival, and independent analysis. Additionally, the association of the ARSig with the tumor immune microenvironment, tumor mutational burden (TMB), and therapeutic response in STS were further investigated. Notably, we finally conducted in vitro experiments to verify the findings from the bioinformatics analysis. ResultsA novel ARSig is successfully constructed and validated. The STS with a lower ARSig risk score in the training cohort has an improved prognosis. Also, consistent results were observed in the internal and external cohorts. The receiver operating characteristic (ROC) curve, subgroup survival, and independent analysis further indicate that the novel ARSig is a promising independent prognostic predictor for STS. Furthermore, it is proved that the novel ARSig is relevant to the immune landscape, TMB, immunotherapy, and chemotherapy sensitivity in STS. Encouragingly, we also validate that the signature ARGs are significantly dysregulated in STS, and ARDB2 and SRPK1 are closely connected with the malignant progress of STS cells. ConclusionIn sum, we construct a novel ARSig for STS, which could act as a promising prognostic factor for STS and give a strategy for future clinical decisions, immune landscape, and personalized treatment of STS.

Automated summary

Given the poor prognosis of soft tissue sarcoma (STS), this study aimed to explore the association of angiogenesis-related genes (ARGs) with STS and establish a novel angiogenesis-related signature (ARSig). The ARSig was validated as a promising prognostic factor for STS and was found to be relevant to the tumor immune microenvironment, tumor mutational burden (TMB), and therapeutic response. In vitro experiments further confirmed the dysregulation of signature ARGs and their role in the malignant progression of STS cells. This study provides a new strategy for prognostic assessment and personalized treatment of STS.