Wei Yani, Li Hongjun, He Shujin, Li Min, Chen Yongyu, Shi Huijuan, Han Anjia
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Front Mol Biosci. 2025 Jul 1;12:1591644. doi: 10.3389/fmolb.2025.1591644. eCollection 2025.
Undifferentiated spindle cell sarcoma (USCS) is a rare and heterogeneous group without specific diagnostic, prognostic, or predictive markers. The clinicopathologic and proteomic characteristics of USCS remain largely unknown.
Between 2008 and 2024, we collected 14 low-grade USCSs and 104 undifferentiated pleomorphic sarcomas (UPSs). We conducted a comprehensive mass spectrometry (MS) proteomic analysis on USCSs and compared the clinicopathologic characteristics of low-grade USCSs and UPSs. More than 5600 proteins could be identified.
Low-grade USCSs had 353 upregulated and 500 downregulated proteins compared to corresponding normal tissue. PHRF1, DIDO1, RAPH1, GGT7, and PHF14 exhibited overexpression in low-grade USCSs, whereas SERPINF2, TMEM40, FYCO1, COL2A1, and NPNT demonstrated low expression. The KEGG pathway enrichment analysis revealed that most of the enriched pathways in low-grade USCS were related to various amino acid and lipid metabolic. Correlating significantly changed proteins with their targeting medications revealed novel therapy options for low-grade USCSs. Furthermore, in comparison to UPSs, our findings indicate that low-grade USCSs may exhibit smaller sizes and a lower rate of distant metastasis. In summary, to the best of our knowledge, this is the first in-depth proteomic analysis to demonstrate a comprehensive investigation of the clinicopathological and proteomic characteristics of low-grade USCSs.
We initially elucidated the characteristics of differential proteins, the pathways enriched, and their possible drug targets in low-grade USCSs. Data are available via ProteomeXchange with identifier PXD061644.
未分化梭形细胞肉瘤（USCS）是一种罕见且异质性的肿瘤群体，缺乏特异性的诊断、预后或预测标志物。USCS的临床病理和蛋白质组学特征在很大程度上仍不清楚。
在2008年至2024年期间，我们收集了14例低级别USCS和104例未分化多形性肉瘤（UPS）。我们对USCS进行了全面的质谱（MS）蛋白质组学分析，并比较了低级别USCS和UPS的临床病理特征。可鉴定出超过5600种蛋白质。
与相应的正常组织相比，低级别USCS有353种上调蛋白和500种下调蛋白。PHRF1、DIDO1、RAPH1、GGT7和PHF14在低级别USCS中表现为过表达，而SERPINF2、TMEM40、FYCO1、COL2A1和NPNT表现为低表达。KEGG通路富集分析显示，低级别USCS中大多数富集通路与各种氨基酸和脂质代谢有关。将显著变化的蛋白质与其靶向药物相关联，揭示了低级别USCS的新治疗选择。此外，与UPS相比，我们的研究结果表明，低级别USCS可能表现为更小的尺寸和更低的远处转移率。总之，据我们所知，这是首次进行深入的蛋白质组学分析，以全面研究低级别USCS的临床病理和蛋白质组学特征。
我们初步阐明了低级别USCS中差异蛋白的特征、富集的通路及其可能的药物靶点。数据可通过ProteomeXchange获得，标识符为PXD061644。
