文章：

一项队列研究：外周血可溶性免疫检查点相关蛋白与骨肉瘤患者生存及治疗效果相关

Peripheral Soluble Immune Checkpoint-Related Proteins Were Associated with Survival and Treatment Efficacy of Osteosarcoma Patients, a Cohort Study

原文发布日期：24 April 2024

DOI: 10.3390/cancers16091628

类型: Article

开放获取: 是

英文摘要：

Background: The immune checkpoint blockade remains obscure in osteosarcoma (OS). We aim to explore the clinical significance of soluble immune checkpoint (ICK)-related proteins in OS. Methods: We profiled 14 soluble ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, CD28, CD80, CD137, CD27, and CTLA-4) in the plasma of 76 OS patients and matched controls. We evaluated the associations between the biomarkers and the risk of OS using unconditional multivariate logistic regression. The multivariate Cox model was utilized to develop the prediction model of OS. Immune subtypes were established from the identified biomarkers. Transcriptional data from GEO were analyzed to elucidate potential mechanisms. Results: We found that sTIM3, sCD137, sIDO, and sCTLA4 were significantly correlated with OS risk (allp< 0.05). sBTLA, sPDL2, and sCD27 were significantly associated with the risk of lung metastasis, whereas sBTLA and sTIM3 were associated with the risk of disease progression. We also established an immune subtype based on sBTLA, sPD1, sTIM3, and sPDL2. Patients in the sICK-type2 subtype had significantly decreased progression-free survival (PFS) and lung metastasis-free survival (LMFS) than those in the sICK-type1 subtype (log-rankp= 2.8 × 10−2, 1.7 × 10−2, respectively). Interestingly, we found that the trend of LMFS and PFS in the subtypes of corresponding ICK genes’ expression was opposite to the results in the blood (log-rankp= 2.6 × 10−4, 9.5 × 10−4, respectively). Conclusion: Four soluble ICK-related proteins were associated with the survival of OS patients. Soluble ICK-related proteins could be promising biomarkers for the outcomes and immunotherapy of OS patients, though more research is warranted.

摘要翻译： 

背景：免疫检查点阻断在骨肉瘤（OS）中的作用机制尚不明确。本研究旨在探讨可溶性免疫检查点（ICK）相关蛋白在骨肉瘤中的临床意义。方法：我们检测了76例骨肉瘤患者及匹配对照者血浆中14种可溶性ICK相关蛋白（BTLA、GITR、HVEM、IDO、LAG-3、PD-1、PD-L1、PD-L2、TIM-3、CD28、CD80、CD137、CD27和CTLA-4）的表达谱。采用非条件多因素逻辑回归分析评估生物标志物与骨肉瘤风险的相关性，并利用多因素Cox模型构建骨肉瘤预测模型。基于鉴定的生物标志物建立免疫亚型，同时分析GEO数据库转录组数据以阐明潜在机制。结果：研究发现sTIM3、sCD137、sIDO和sCTLA4与骨肉瘤风险显著相关（均p<0.05）。sBTLA、sPDL2和sCD27与肺转移风险显著相关，而sBTLA和sTIM3与疾病进展风险相关。基于sBTLA、sPD1、sTIM3和sPDL2建立的免疫亚型分析显示，sICK-type2亚型患者的无进展生存期（PFS）和无肺转移生存期（LMFS）较sICK-type1亚型显著缩短（对数秩检验p值分别为2.8×10⁻²、1.7×10⁻²）。值得注意的是，相应ICK基因表达亚型中LMFS和PFS的变化趋势与血液检测结果相反（对数秩检验p值分别为2.6×10⁻⁴、9.5×10⁻⁴）。结论：四种可溶性ICK相关蛋白与骨肉瘤患者生存相关。可溶性ICK相关蛋白有望成为骨肉瘤患者预后及免疫治疗的潜在生物标志物，但尚需进一步研究验证。

原文链接：

Peripheral Soluble Immune Checkpoint-Related Proteins Were Associated with Survival and Treatment Efficacy of Osteosarcoma Patients, a Cohort Study