血管肉瘤是一种临床上具有侵袭性的内皮源性癌症，是一种罕见的软组织肉瘤亚型，其特点是对化疗耐药和预后不良。在这项研究中，我们的目的是鉴定血管肉瘤化疗耐药的转录组生物标志物。我们检查了 72 例亚洲血管肉瘤病例，其中 35 例接受姑息化疗，整合了 NanoString 基因表达谱、全转录组谱 (RNA-seq)、免疫组织化学、细胞系分析和临床病理学数据的信息。在化疗耐药队列（定义为疾病稳定或进展）中，我们观察到基因显着过度表达，包括 SPP1（log2foldchange 3.49，adj. p = 0.0112）、CXCL13、CD48 和 CLEC5A，同时伴随着髓系区室和骨髓细胞的显着富集。细胞因子和趋化因子信号传导途径，以及中性粒细胞和巨噬细胞。 RNA-seq 数据显示，肿瘤组织中的 SPP1 表达量 (p = 0.0008) 高于邻近的正常区室。免疫组织化学显示，SPP1 蛋白与基因表达之间存在显着的中度正相关（r = 0.7016；p < 0.00110），而患者来源的血管肉瘤细胞系 MOLAS 和 ISOHAS 中较高的 SPP1 蛋白表达与较低的化疗敏感性相关。此外，SPP1 mRNA过表达与上皮样组织学（p = 0.007）、较高的肿瘤分级（p = 0.0023）、非头颈部位置（p = 0.0576）以及较差的总生存结果（HR 1.84，95% CI）呈正相关。 1.07-3.18，p = 0.0288）。与肿瘤突变负荷、肿瘤炎症特征、人类疱疹病毒 7 的存在、紫外线暴露特征和诊断时的转移状态没有关联。总之，SPP1 过表达可能是血管肉瘤化疗耐药和不良预后的生物标志物。需要进一步研究来揭示 SPP1 的确切作用和潜在机制。

Angiosarcomas, clinically aggressive cancers of endothelial origin, are a rare subtype of soft-tissue sarcomas characterized by resistance to chemotherapy and dismal prognosis. In this study, we aim to identify the transcriptomic biomarkers of chemoresistance in angiosarcoma. We examined 72 cases of Asian angiosarcomas, including 35 cases treated with palliative chemotherapy, integrating information from NanoString gene expression profiling, whole transcriptome profiling (RNA-seq), immunohistochemistry, cell line assays, and clinicopathological data. In the chemoresistant cohort (defined as stable disease or progression), we observed the significant overexpression of genes, including SPP1 (log2foldchange 3.49, adj. p = 0.0112), CXCL13, CD48, and CLEC5A, accompanied by the significant enrichment of myeloid compartment and cytokine and chemokine signaling pathways, as well as neutrophils and macrophages. RNA-seq data revealed higher SPP1 expression (p = 0.0008) in tumor tissues over adjacent normal compartments. Immunohistochemistry showed a significant moderate positive correlation between SPP1 protein and gene expression (r = 0.7016; p < 0.00110), while higher SPP1 protein expression correlated with lower chemotherapeutic sensitivity in patient-derived angiosarcoma cell lines MOLAS and ISOHAS. In addition, SPP1 mRNA overexpression positively correlated with epithelioid histology (p = 0.007), higher tumor grade (p = 0.0023), non-head and neck location (p = 0.0576), and poorer overall survival outcomes (HR 1.84, 95% CI 1.07-3.18, p = 0.0288). There was no association with tumor mutational burden, tumor inflammation signature, the presence of human herpesvirus-7, ultraviolet exposure signature, and metastatic state at diagnosis. In conclusion, SPP1 overexpression may be a biomarker of chemoresistance and poor prognosis in angiosarcoma. Further investigation is needed to uncover the precise roles and underlying mechanisms of SPP1.