Baseline differences in metabolic profiles of patients with lung squamous cell carcinoma responding or not responding to treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel)

Peng Cao, Qilin Zhang, Sanlan Wu, Mitchell A. Sullivan, Yifei Huang, Weijing Gong, Yongning Lv, Xuejia Zhai, Yu Zhang
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Abstract

Background: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a preparation widely used in chemotherapy for cancers. However, only some patients benefit from this treatment. Therefore, identifying which patients will respond to nab-paclitaxel therapy is crucial. Methods: A cohort of 32 patients with lung squamous cell carcinoma (LUSC) treated with nab-paclitaxel were enrolled in this study. Plasma samples were collected before chemotherapy and used to perform metabolomic and lipidomic analyses. Tumor response to two cycles of chemotherapy was evaluated. Metabolites differentially present among populations were screened and analyzed. Results: According to the RECIST criteria, one-third of patients had a significant response to nab-paclitaxel, whereas one-fifth showed no discernible benefit. According to the criteria of variable importance in projection >1 and fold change >2, we identified 61, 81 and 54 differential metabolites between the progressive disease (PD) vs partial response (PR), PD vs stable disease (SD), and SD vs PR groups, respectively. Moreover, we used three variation in logistic regression models and ROC diagnostic curves to identify optimal metabolites for stratifying patients with differing chemotherapeutic responses. The PD vs SD, SD vs PR, and PD vs PR groups were well separated on the basis of cis-9,10-epoxystearic acid/octapentaenoic acid (AUC 0.9330), salicyluric acid/DG (18:1/20:5/0:0) (AUC 1.0000) and D-glyceric acid/9,12-octadecadienoic acid (AUC 1.0000), respectively. Conclusion: The baseline metabolic profiles significantly differed between responder and non-responder patients with LUSC treated with nab-paclitaxel. These differential metabolites have the potential to predict the outcomes of patients with LUSC before chemotherapy.
纳米颗粒白蛋白结合紫杉醇(nab-paclitaxel)治疗对肺鳞癌患者代谢谱的基线差异
背景:纳米白蛋白结合紫杉醇(nab-paclitaxel)是一种广泛应用于癌症化疗的制剂。然而,只有一些患者从这种治疗中受益。因此,确定哪些患者对nab-紫杉醇治疗有反应是至关重要的。方法:32例肺鳞状细胞癌(LUSC)患者接受nab-紫杉醇治疗。化疗前收集血浆样本,用于进行代谢组学和脂质组学分析。评估肿瘤对两个化疗周期的反应。筛选并分析了不同人群代谢物的差异。结果:根据RECIST标准,三分之一的患者对nab-紫杉醇有显著反应,而五分之一的患者没有明显的益处。根据投射(projection) >1和fold change >2的可变重要性标准,我们分别在进展性疾病(PD)与部分缓解(PR)、PD与稳定性疾病(SD)、SD与PR组之间鉴定出61、81和54种差异代谢物。此外,我们在logistic回归模型和ROC诊断曲线中使用了三种变异来确定最佳代谢物,以对不同化疗反应的患者进行分层。以顺式-9,10-环氧硬脂酸/八烯酸(AUC 0.9330)、水杨酸/DG (18:1/20:5/0:0) (AUC 1.0000)和d -甘油酸/9,12-十八烯酸(AUC 1.0000)为基础,PD组与SD组、SD组与PR组、PD组与PR组进行了较好的分离。结论:nab-紫杉醇治疗有反应和无反应的LUSC患者的基线代谢谱有显著差异。这些差异代谢物有可能预测化疗前LUSC患者的预后。
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