Year-end Sale % OFF 
Abstract
Simple SummarySoft tissue sarcomas (STS) still lack effective clinical stratification and prognostic models. The aim of this study is to establish a reliable prognostic gene signature in STS. Using 189 STS samples from the TCGA database, a four-gene signature (including DHRS3, JRK, TARDBP and TTC3) and nomograms that can be used to predict the overall survival and relapse free survival of STS patients was developed. The predictive ability for metastasis free survival was externally verified in the GEO cohort. We demonstrated that the novel gene signature provides an attractive platform for risk stratification and prognosis prediction of STS patients, which is of great importance for individualized clinical treatment and long-term management of patients with this rare and severe disease.Soft tissue sarcomas (STS), a group of rare malignant tumours with high tissue heterogeneity, still lack effective clinical stratification and prognostic models. Therefore, we conducted this study to establish a reliable prognostic gene signature. Using 189 STS patients’ data from The Cancer Genome Atlas database, a four-gene signature including DHRS3, JRK, TARDBP and TTC3 was established. A risk score based on this gene signature was able to divide STS patients into a low-risk and a high-risk group. The latter had significantly worse overall survival (OS) and relapse free survival (RFS), and Cox regression analyses showed that the risk score is an independent prognostic factor. Nomograms containing the four-gene signature have also been established and have been verified through calibration curves. In addition, the predictive ability of this four-gene signature for STS metastasis free survival was verified in an independent cohort (309 STS patients from the Gene Expression Omnibus database). Finally, Gene Set Enrichment Analysis indicated that the four-gene signature may be related to some pathways associated with tumorigenesis, growth, and metastasis. In conclusion, our study establishes a novel four-gene signature and clinically feasible nomograms to predict the OS and RFS. This can help personalized treatment decisions, long-term patient management, and possible future development of targeted therapy.
Highlights
Soft tissue sarcomas (STS) are a group of rare malignant tumours mainly derived from the embryonic mesoderm, with high tissue heterogeneity in each subtype, that represent 2% of all adult, and 7% of all childhood cancers [1,2]
A robust likelihood-based survival analysis was performed on 95 samples in the training set and obtained 22 genes that are significantly related to overall survival (OS)
The four genes identified in this context were dehydrogenase/reductase 3 (DHRS3), Jrk helix-turn-helix protein (JRK), TAR DNA binding protein (TARDBP) and tetratricopeptide repeat domain 3 (TTC3)
Summary
Soft tissue sarcomas (STS) are a group of rare malignant tumours mainly derived from the embryonic mesoderm, with high tissue heterogeneity in each subtype, that represent 2% of all adult, and 7% of all childhood cancers [1,2]. Surgical resection with radiotherapy is the most effective treatment strategy for early localized STS, and chemotherapy is usually indicated for patients with metastatic tumours [6,7,8]. Previous studies have shown that risk stratification and targeted therapy can significantly improve the treatment effect for most tumours, and STS is no exception [9,10]. Molecular biomarkers play a key role in prognosis and treatment decisions for a variety of tumours; for example, PD-1 and PD-L1 are prognostic markers for a variety of tumours, and key indicators for immune checkpoint therapy [12]. In STS, molecular signatures, including hypoxia-related gene signatures, have been shown to play a role in risk classification [13]. The identification of new molecular signatures and their combination with existing predictors is expected to improve the identification of “high-risk” patients [14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
