Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Division of Hematology, The Ohio State University, Columbus, Ohio, USA.
Br J Haematol. 2022 Oct;199(1):100-105. doi: 10.1111/bjh.18336. Epub 2022 Jun 29.
Older patients with cancer often receive treatment regimens based on their age without considering other objective factors that may influence outcomes. Assessment of frailty can identify older patients who are robust and therefore more likely to benefit from intensive treatment, or conversely, frail and might instead be offered alternative approaches. However, such assessment requires specialised training and dedicated clinical resources. Alternative quantitative biomarkers associated with frailty are lacking. Here, we asked if expression signatures of 74 immune cell, ageing, and senescence-related messenger RNAs in purified peripheral blood T cells could identify associations with clinical frailty in patients with haematological malignancies. We studied 69 patients between the ages of 36 and 92 years (median 76 years) with leukaemia, lymphoma, or multiple myeloma, across two institutions. Expression of four genes (aryl hydrocarbon receptor [AHR], CD27, CD28, and interleukin-2 receptor subunit alpha [IL2RA; CD25]) in T cells was associated with frailty, independent of age. An expression-based regression model had 76% sensitivity and 90% specificity to assign a patient as robust. These data identify measurable peripheral blood correlates of clinical frailty and suggest biomarkers for future prospective assessment.
老年癌症患者的治疗方案往往基于其年龄制定，而不考虑可能影响结果的其他客观因素。衰弱评估可以识别出身体强壮的老年患者，他们更有可能从强化治疗中获益，或者相反，身体虚弱的患者可能会选择替代方法。然而，这种评估需要专门的培训和专门的临床资源。与衰弱相关的替代定量生物标志物尚缺乏。在这里，我们询问了在纯化的外周血 T 细胞中表达的 74 种免疫细胞、衰老和衰老相关信使 RNA 的特征是否可以识别与血液系统恶性肿瘤患者临床虚弱的关联。我们研究了来自两个机构的 69 名年龄在 36 岁至 92 岁之间（中位数为 76 岁）的白血病、淋巴瘤或多发性骨髓瘤患者。T 细胞中四个基因（芳烃受体 [AHR]、CD27、CD28 和白细胞介素 2 受体亚单位 alpha [IL2RA；CD25]）的表达与虚弱有关，与年龄无关。基于表达的回归模型对患者的强壮程度具有 76%的敏感性和 90%的特异性。这些数据确定了可测量的临床虚弱的外周血液相关因素，并为未来的前瞻性评估提供了生物标志物。
