Miolo Gianmaria, Di Gregorio Emanuela, Saorin Asia, Lombardi Davide, Scalone Simona, Buonadonna Angela, Steffan Agostino, Corona Giuseppe
Medical Oncology and Cancer Prevention Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
Cancers (Basel). 2020 Jul 21;12(7):1983. doi: 10.3390/cancers12071983.
Soft tissue sarcomas (STS) are a group of rare and heterogeneous cancers with few diagnostic or prognostic biomarkers. This metabolomics study aimed to identify new serum prognostic biomarkers to improve the prediction of overall survival in patients with metastatic STS. The study enrolled 24 patients treated with the same trabectedin regimen. The baseline serum metabolomics profile, targeted to 68 metabolites encompassing amino acids and bile acids pathways, was quantified by liquid chromatography-tandem mass spectrometry. Correlations between individual metabolomics profiles and overall survival were examined and a risk model to predict survival was built by Cox multivariate regression. The median overall survival of the studied patients was 13.0 months (95% CI, 5.6-23.5). Among all the metabolites investigated, only citrulline and histidine correlated significantly with overall survival. The best Cox risk prediction model obtained integrating metabolomics and clinical data, included citrulline, hemoglobin and patients' performance status score. It allowed to distinguish patients into a high-risk group with a low median overall survival of 2.1 months and a low- to moderate-risk group with a median overall survival of 19.1 months ( < 0.0001). The results of this metabolomics translation study indicate that citrulline, an amino acid belonging to the arginine metabolism, represents an important metabolic signature that may contribute to explain the high inter-patients overall survival variability of STS patients. The risk prediction model based on baseline serum citrulline, hemoglobin and performance status may represent a new prognostic tool for the early classification of patients with metastatic STS, according to their overall survival expectancy.
软组织肉瘤（STS）是一组罕见且异质性的癌症，几乎没有诊断或预后生物标志物。这项代谢组学研究旨在识别新的血清预后生物标志物，以改善转移性STS患者总生存期的预测。该研究纳入了24例接受相同曲贝替定治疗方案的患者。通过液相色谱-串联质谱法定量分析了针对68种代谢物的基线血清代谢组学谱，这些代谢物涵盖氨基酸和胆汁酸途径。研究了个体代谢组学谱与总生存期之间的相关性，并通过Cox多变量回归建立了预测生存期的风险模型。研究患者的中位总生存期为13.0个月（95%CI，5.6 - 23.5）。在所有研究的代谢物中，只有瓜氨酸和组氨酸与总生存期显著相关。整合代谢组学和临床数据得到的最佳Cox风险预测模型包括瓜氨酸、血红蛋白和患者的体能状态评分。它能够将患者分为中位总生存期低至2.1个月的高风险组和中位总生存期为19.1个月的低至中度风险组（<0.0001）。这项代谢组学转化研究的结果表明，瓜氨酸作为精氨酸代谢中的一种氨基酸，代表了一种重要的代谢特征，可能有助于解释STS患者之间总生存期的高变异性。基于基线血清瓜氨酸、血红蛋白和体能状态的风险预测模型可能代表一种新的预后工具，可根据总生存预期对转移性STS患者进行早期分类。
