Ceramide metabolism-related prognostic signature and immunosuppressive function of ST3GAL1 in osteosarcoma.
Ceramide metabolism-related prognostic signature and immunosuppressive function of ST3GAL1 in osteosarcoma.
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DOI：
10.1016/j.tranon.2023.101840
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发表时间：
2024-02
影响因子：
5
通讯作者：
Xie, Xianbiao
中科院分区：
文献类型：
--
作者：
Zou, Yutong;Guo, Siyao;Liao, Yan;Chen, Weidong;Chen, Ziyun;Chen, Junkai;Wen, Lili;Xie, Xianbiao
神经酰胺代谢相关信号预测骨肉瘤预后。ST 3GAL 1与TAM诱导的CD 8 + T细胞毒性功能抑制相关。ST 3GAL 1通过α 2，3-连接的唾液酸受体调节TAMs-CD 8 + T相互作用。肿瘤细胞中的ST 3GAL 1调节TAM分化。骨肉瘤是儿童和青少年最常见的原发性恶性骨肿瘤，致残率和死亡率较高，在过去的30年里，骨肉瘤的治疗效果一直停滞不前。新的证据表明神经酰胺代谢在肿瘤进展中起着至关重要的作用，但其在骨肉瘤进展中的机制尚不清楚。通过基于TARGET数据库中骨肉瘤队列的一致聚类和LASSO回归分析，我们构建了包括10个骨肉瘤基因的神经酰胺代谢相关预后特征，其中ST 3GAL 1表现出最高的风险比。生物学特征分析表明，神经酰胺代谢与免疫相关通路、免疫细胞浸润和免疫检查点基因表达相关。单细胞分析显示，神经酰胺代谢富集在骨髓，成骨细胞和间充质细胞。TAMs与CD 8 + T细胞的相互作用在骨肉瘤中起着重要作用。ST 3GAL 1通过α 2，3唾液酸受体调节TAM与CD 8 + T细胞之间的SPP 1-CD 44相互作用以及TAM中IL-10的分泌，从而抑制CD 8 + T细胞的功能。免疫组化分析显示ST 3GAL 1表达与骨肉瘤患者的预后相关。共培养实验表明，ST 3GAL 1在肿瘤细胞中的上调调节TAM的分化和细胞因子的分泌。总的来说，我们的研究结果表明，神经酰胺代谢与骨肉瘤的临床结果有关。ST 3GAL 1通过调节肿瘤免疫微环境促进肿瘤进展，为骨肉瘤患者提供了一种可行的治疗途径。
Ceramide metabolism-related signature predict prognosis in osteosarcoma. ST3GAL1 associated with TAMs-induced inhibition of CD8+ T cytotoxic function. ST3GAL1 regulated TAMs-CD8+ T interaction through α2,3-linked sialic acid receptors. ST3GAL1 in tumor cells regulated TAMs differentiation. Osteosarcoma is the most common primary malignant bone tumor with elevated disability and mortality rates in children and adolescents and the therapeutic effect for osteosarcoma has remained stagnant in the past 30 years. Emerging evidence has shown ceramide metabolism plays a vital role in tumor progression, but its mechanisms in osteosarcoma progression remain unknown. Through consensus clustering and LASSO regression analysis based on the osteosarcoma cohorts from TARGET database, we constructed a ceramide metabolism-related prognostic signature including ten genes for osteosarcoma, with ST3GAL1 exhibiting the highest hazard ratio. Biological signatures analysis demonstrated that ceramide metabolism was associated with immune-related pathways, immune cell infiltration and the expression of immune checkpoint genes. Single-cell profiling revealed that ceramide metabolism was enriched in myeloid, osteoblast and mesenchymal cells. The interaction between TAMs and CD8+ T cells played an essential role in osteosarcoma. ST3GAL1 regulated the SPP1-CD44 interaction between TAMs and CD8+ T cells and IL-10 secretion in TAMs through α2,3 sialic acid receptors, which inhibited CD8+ T cell function. IHC analysis showed that ST3GAL1 expression correlated with the prognosis of osteosarcoma patients. Co-culture assay revealed that upregulation of ST3GAL1 in tumor cells regulated the differentiation of TAMs and cytokine secretion. Collectively, our findings demonstrated that ceramide metabolism was associated with clinical outcome in osteosarcoma. ST3GAL1 facilitated tumor progression through regulating tumor immune microenvironment, providing a feasible therapeutic approach for patients with osteosarcoma.
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影响因子：
29.4
作者：
Li G;Liu D;Kimchi ET;Kaifi JT;Qi X;Manjunath Y;Liu X;Deering T;Avella DM;Fox T;Rockey DC;Schell TD;Kester M;Staveley-O'Carroll KF
通讯作者：
Staveley-O'Carroll KF
影响因子：
64.8
作者：
Cronin SJF;Seehus C;Weidinger A;Talbot S;Reissig S;Seifert M;Pierson Y;McNeill E;Longhi MS;Turnes BL;Kreslavsky T;Kogler M;Hoffmann D;Ticevic M;da Luz Scheffer D;Tortola L;Cikes D;Jais A;Rangachari M;Rao S;Paolino M;Novatchkova M;Aichinger M;Barrett L;Latremoliere A;Wirnsberger G;Lametschwandtner G;Busslinger M;Zicha S;Latini A;Robson SC;Waisman A;Andrews N;Costigan M;Channon KM;Weiss G;Kozlov AV;Tebbe M;Johnsson K;Woolf CJ;Penninger JM
通讯作者：
Penninger JM
影响因子：
4.9
作者：
Dhule SS;Penfornis P;He J;Harris MR;Terry T;John V;Pochampally R
通讯作者：
Pochampally R
影响因子：
11.1
作者：
Moon JY;Zolnik CP;Wang Z;Qiu Y;Usyk M;Wang T;Kizer JR;Landay AL;Kurland IJ;Anastos K;Kaplan RC;Burk RD;Qi Q
通讯作者：
Qi Q
影响因子：
48
作者：
Korsunsky, Ilya;Millard, Nghia;Raychaudhuri, Soumya
通讯作者：
Raychaudhuri, Soumya