Department of Health Statistics, Key Laboratory of Medicine and Health of Shandong Province, School of Public Health, Weifang Medical University, Weifang, Shandong 261053, China.
Tianjin Cancer Institute, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
Aging (Albany NY). 2021 Nov 8;13(21):24155-24170. doi: 10.18632/aging.203671.
Osteosarcoma (OS) is the most common bone cancer, mainly diagnosed in children and adolescents. So far, no reliable molecular biomarkers have been identified to effectively evaluate OS prognosis and immune infiltration. Herein, we curated transcriptome profiles and clinical information from the publicly available OS cohorts to establish an immune-related prognostic signature. Besides, immunotherapeutic cohorts of urothelial cancer and melanoma patients were also employed to infer immunotherapy prediction roles of the identified signature. Lymphocytes infiltration, immune response-related pathways and signatures in the microenvironment were assessed according to distinct risk subgroups. Based on the univariate Cox analysis and further feature selection implemented by the LASSO regression model in the TARGET cohort, a 21-immune-gene signature was identified by combing the expression values and corresponding coefficients. We observed that the low-risk score of this signature was significantly linked with the preferable survival outcome (Log-rank test < 0.001). The consistent results of better prognoses of the low-risk group were also obtained in subsequent two validation cohorts. Immunology analyses showed that favorable immune infiltration and elevated enrichment of immune response signals may contribute to the better outcome of the low-risk OS subgroup. The immunotherapeutic efficacy analyses demonstrated that low-risk patients harbored significantly enhanced response rates and improved immunotherapy survival outcomes. Together, our established signature could evaluate survival risk and represent the immune microenvironment status of OS, which promotes precision treatment and provides a potential biomarker for prognosis prediction and immunotherapy efficacy assessment.
骨肉瘤（OS）是最常见的骨癌，主要发生在儿童和青少年中。到目前为止，还没有可靠的分子生物标志物来有效评估 OS 的预后和免疫浸润。在此，我们从公开的 OS 队列中整理了转录组谱和临床信息，以建立一个与免疫相关的预后特征。此外，还利用了膀胱癌和黑色素瘤患者的免疫治疗队列来推断所确定特征的免疫治疗预测作用。根据不同的风险亚组评估了淋巴细胞浸润、免疫反应相关途径和微环境中的特征。基于 TARGET 队列中的单因素 Cox 分析和 LASSO 回归模型进一步进行特征选择，通过结合表达值和相应系数，确定了一个 21 个免疫基因特征。我们观察到该特征的低风险评分与更好的生存结果显著相关（对数秩检验<0.001）。在随后的两个验证队列中，也得到了低风险组预后更好的一致结果。免疫分析表明，有利的免疫浸润和升高的免疫反应信号富集可能有助于低风险 OS 亚组的更好结局。免疫治疗疗效分析表明，低风险患者的反应率显著提高，免疫治疗的生存结果得到改善。总之，我们建立的特征可以评估 OS 的生存风险和代表其免疫微环境状态，从而促进精准治疗，并为预后预测和免疫治疗效果评估提供潜在的生物标志物。
