Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Front Immunol. 2022 Dec 9;13:1071636. doi: 10.3389/fimmu.2022.1071636. eCollection 2022.
Osteosarcoma (OS) is a highly aggressive bone malignancy with a poor prognosis, mainly in children and adolescents. Immunogenic cell death (ICD) is classified as a type of programmed cell death associated with the tumor immune microenvironment, prognosis, and immunotherapy. However, the feature of the ICD molecular subtype and the related tumor microenvironment (TME) and immune cell infiltration has not been carefully investigated in OS.
The ICD-related genes were extracted from previous studies, and the RNA expression profiles and corresponding data of OS were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus database. The ICD-related molecular subtypes were classed by the "ConsensusclusterPlus" package and the construction of ICD-related signatures through univariate regression analysis. ROC curves, independent analysis, and internal validation were used to evaluate signature performance. Moreover, a series of bioinformatic analyses were used for Immunotherapy efficacy, tumor immune microenvironments, and chemotherapeutic drug sensitivity between the high- and low-risk groups.
Herein, we identified two ICD-related subtypes and found significant heterogeneity in clinical prognosis, TME, and immune response signaling among distinct ICD subtypes. Subsequently, a novel ICD-related prognostic signature was developed to determine its predictive performance in OS. Also, a highly accurate nomogram was then constructed to improve the clinical applicability of the novel ICD-related signature. Furthermore, we observed significant correlations between ICD risk score and TME, immunotherapy response, and chemotherapeutic drug sensitivity. Notably, the in vitro experiments further verified that high GALNT14 expression is closely associated with poor prognosis and malignant progress of OS.
Hence, we identified and validated that the novel ICD-related signature could serve as a promising biomarker for the OS's prognosis, chemotherapy, and immunotherapy response prediction, providing guidance for personalized and accurate immunotherapy strategies for OS.
骨肉瘤（OS）是一种高度侵袭性的骨恶性肿瘤，预后较差，主要发生在儿童和青少年。免疫原性细胞死亡（ICD）被归类为与肿瘤免疫微环境、预后和免疫治疗相关的一种程序性细胞死亡。然而，在骨肉瘤中，ICD 分子亚型的特征以及相关的肿瘤微环境（TME）和免疫细胞浸润尚未得到仔细研究。
从先前的研究中提取了 ICD 相关基因，并从癌症基因组图谱和基因表达综合数据库下载了骨肉瘤的 RNA 表达谱和相应数据。使用“ConsensusclusterPlus”包对 ICD 相关分子亚型进行分类，并通过单变量回归分析构建 ICD 相关特征。使用 ROC 曲线、独立分析和内部验证来评估特征性能。此外，还进行了一系列生物信息学分析，以评估高低风险组之间免疫治疗效果、肿瘤免疫微环境和化疗药物敏感性的差异。
在这里，我们确定了两种 ICD 相关亚型，并发现不同 ICD 亚型之间在临床预后、TME 和免疫反应信号方面存在显著的异质性。随后，开发了一种新的 ICD 相关预后特征，以确定其在骨肉瘤中的预测性能。此外，还构建了一个高度准确的列线图，以提高新的 ICD 相关特征的临床适用性。此外，我们观察到 ICD 风险评分与 TME、免疫治疗反应和化疗药物敏感性之间存在显著相关性。值得注意的是，体外实验进一步验证了高 GALNT14 表达与骨肉瘤的不良预后和恶性进展密切相关。
因此，我们鉴定和验证了新的 ICD 相关特征可以作为骨肉瘤预后、化疗和免疫治疗反应预测的有前途的生物标志物，为骨肉瘤的个性化和精准免疫治疗策略提供指导。
