Soft tissue sarcoma (STS) represents an uncommon and heterogenous group of malignancies, and poses substantial therapeutic challenges. Pyroptosis has been demonstrated to be related with tumor progression and prognosis. Nevertheless, no studies exist that delineated the role of pyroptosis-related genes (PRGs) in STS. In the present study, we comprehensively and systematically analyzed the gene expression profiles of PRGs in STS. The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were utilized to identify differentially expressed PRGs. In total, 34 PRGs were aberrantly expressed between STS and normal tissues. Several PRGs were validated with RT-qPCR. Consensus clustering analysis based on PRGs was conducted to divide STS patients into two clusters, and significant survival difference was observed between two distinct clusters (p = 0.019). Differentially expressed genes (DEGs) were identified between pyroptosis-related clusters. Based on the least absolute shrinkage and selection operator (LASSO) COX regression analysis, the pyroptosis-related gene signature with five key DEGs was constructed. The high pyroptosis-related risk score group of TCGA cohort was characterized by poorer prognosis (p < 0.001), with immune infiltration and function significantly decreased. For external validation, STS patients from Gene Expression Omnibus (GEO) were grouped according to the same cut-off point. The survival difference between two risk groups of GEO cohort was also significant (p < 0.001). With the combination of clinical characteristics, pyroptosis-related risk score was identified to serve as an independent prognostic factor for STS patients. In conclusion, this study provided a comprehensive overview of PRGs in STS and the potential role in prognosis, which could be an important direction for future studies.

Denosumab is a monoclonal antibody that targets and inhibits the osteoclast activating factor receptor activator for nuclear factor-κB ligand (RANKL). It has been widely used in the treatment of osteoporosis, giant cell tumors of bone, and in the prevention of malignant skeletal-related events (SREs). We collected the research results and related MeSH terms of denosumab from 2011 to 2021 through the Web of Science and PubMed, respectively. The literature was visualized and analyzed by CiteSpace and bibliometric online analysis platforms. The MeSH terms were biclustered using the Bibliographic Co-Occurrence Analysis System (BICOMB) and graph clustering toolkit (gCLUTO). The results show that the number of denosumab-related annual publications had increased from 51 to 215, with the United States leading and Amgen Inc. being the most influential in the past 10 years. Articles published in the Journal of Bone and Mineral Research had the highest total citations. Three scholars from Shinshu University in Matsumoto, Yukio Nakamura, Takako Suzuki, and Hiroyuki Kato, joined the field relatively late but produced the most. The clinical comparison and combination of denosumab with other drugs in the treatment of osteoporosis was the most significant focus of research. Drug withdrawal rebound and management strategies have gained more attention and controversy recently. MeSH analysis revealed eight major categories of research hotspots. Among them, exploring the multiple roles of the RANK-RANKL-OPG system in tumor progression, metastasis, and other diseases is the potential direction of future mechanism research. It is a valuable surgical topic to optimize the perioperative drug administration strategy for internal spinal fixation and orthopedic prosthesis implantation. Taken together, the advantages of denosumab were broad and cost-effective. However, there were still problems such as osteonecrosis of the jaw, severe hypocalcemia, a high recurrence rate of giant cells in the treatment of bone and individual sarcoidosis, and atypical femoral fractures, which need to be adequately solved.

Background CircRNAs have emerged as pivotal regulators in osteosarcoma tumorigenesis and progression, but their prognostic and diagnostic significance remain unclear. Herein, we aimed to perform an updated meta-analysis to explore the clinical, diagnostic and prognostic values of circRNAs in osteosarcoma. Methods Several databases, including PubMed, Web of Science, EMBASE, Scopus and Cochrane Library, were systematically searched up to April 10, 2020. Eligible studies regarding the relationship between circRNAs levels and clinicopathological, diagnostic and prognostic values in osteosarcoma patients were included in this study. Pooled odds ratios with corresponding 95% confidence intervals were used to measure clinical characteristics, while hazard ratios with 95% CIs were adopted to assess overall survival (OS) and disease-free survival (DFS). Results Overall, 26 relevant studies involving 1,652 patients with osteosarcoma were enrolled, with eighteen studies on clinicopathological parameters, ten on diagnosis and eighteen on prognosis. For clinical parameters, overexpression of oncogenic circRNAs was intimately correlated with larger tumor size (P < 0.00001), advanced Enneking stage (P < 0.00001), poor differentiation (P = 0.0001), and distant metastasis (DM) (P < 0.00001). In contrast, the downregulated circRNAs showed negative correlation with Enneking stage (P = 0.002) and DM (P < 0.0001). For the diagnostic values, the summary area under the curve of circRNA for the discriminative efficacy between osteosarcoma patients and non-cancer counterparts was estimated to be 0.86 (95% CI: 0.83–0.89), with a weighted sensitivity of 0.80 (95% CI: 0.74–0.84), specificity of 0.80 (95%: 0.75–0.84), and diagnostic odds ratio of 15.48 (10.85–22.10), respectively. For the prognostic significance, oncogenic circRNAs had poor OS (HR = 1.92, 95% CI: 1.68–2.19) and DFS (HR = 2.65, 95% CI: 2.02–3.49), while elevated expression of tumor-suppressor circRNAs were closely related to longer OS (HR = 0.44, 95% CI: 0.28–0.69). Conclusions Taken together, our study showed that aberrantly expressed circRNA signatures could serve as potential biomarkers in diagnosis and prognosis in patients with osteosarcoma.