A pilot study: Metabolic profiling of plasma and saliva samples from newly diagnosed glioblastoma patients.

A pilot study: Metabolic profiling of plasma and saliva samples from newly diagnosed glioblastoma patients.
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DOI:
10.1002/cam4.5857
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发表时间:
2023-05
期刊:
影响因子:
4
通讯作者:
Punyadeera, Chamindie
Punyadeera, Chamindie
中科院分区:
医学3区
文献类型:
--
作者:
Bark, Juliana Muller;Karpe, Avinash V.;Doecke, James D.;Leo, Paul;Jeffree, Rosalind L.;Chua, Benjamin;Day, Bryan W.;Beale, David J.;Punyadeera, Chamindie

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尽管积极治疗,超过90%的胶质母细胞瘤(GBM)患者复发。目前通过成像技术和组织活检评估GBM对治疗的反应。然而,这些方法的困难可能会导致对治疗结果的误解。目前,没有经过验证的治疗反应生物标志物可用于监测GBM进展。代谢组学具有作为补充工具的潜力,以改善治疗反应的解释,以帮助GBM患者的临床干预。术前和术后收集GBM患者的唾液和血液。将患者按照其无进展生存期(PFS)分为有利或不利的临床结局(分别为>9个月或PFS ≤ 9个月)。采用LC-QqQ-MS和LC-QTOF-MS对唾液(全口和口腔冲洗液)和血浆样本进行分析,以确定代谢组学和脂质组学特征。使用单变量和多变量统计分析以及基于图形LASSO的图形网络分析对数据进行了研究。在所有唾液和血浆样本中共检测到151种代谢物和197种脂质。与术前和术后结局良好的患者相比,在结局不利的患者中,代谢产物如环AMP、3-羟基犬尿氨酸、二氢乳清酸盐、UDP和顺乌头酸盐升高。这些代谢物显示影响磷酸戊糖和瓦尔堡效应途径。与有利结局组相比,经历不利结局的患者的脂质谱显示脂质丰度的异质性更高,标志物之间的相关性更少。我们的研究结果表明,GBM患者唾液和血浆代谢物的变化可能被用作侵入性较小的预后生物标志物/生物标志物组,但需要更大的队列进行验证。术前和术后从21例新诊断的GBM患者中采集唾液和血浆样本。采用LC-QqQ-MS和LC-QTOF-MS分析代谢组学和脂质组学特征。根据临床结局(分别为无进展生存期(PFS)> 9个月或PFS ≤ 9个月),将GBM患者分为有利或不利患者。使用单变量和多变量统计分析以及基于图形LASSO的图形网络分析对数据进行了研究。
Despite aggressive treatment, more than 90% of glioblastoma (GBM) patients experience recurrences. GBM response to therapy is currently assessed by imaging techniques and tissue biopsy. However, difficulties with these methods may cause misinterpretation of treatment outcomes. Currently, no validated therapy response biomarkers are available for monitoring GBM progression. Metabolomics holds potential as a complementary tool to improve the interpretation of therapy responses to help in clinical interventions for GBM patients. Saliva and blood from GBM patients were collected pre and postoperatively. Patients were stratified conforming their progression‐free survival (PFS) into favourable or unfavourable clinical outcomes (>9 months or PFS ≤ 9 months, respectively). Analysis of saliva (whole‐mouth and oral rinse) and plasma samples was conducted utilising LC‐QqQ‐MS and LC‐QTOF‐MS to determine the metabolomic and lipidomic profiles. The data were investigated using univariate and multivariate statistical analyses and graphical LASSO‐based graphic network analyses. Altogether, 151 metabolites and 197 lipids were detected within all saliva and plasma samples. Among the patients with unfavourable outcomes, metabolites such as cyclic‐AMP, 3‐hydroxy‐kynurenine, dihydroorotate, UDP and cis‐aconitate were elevated, compared to patients with favourable outcomes during pre‐and post‐surgery. These metabolites showed to impact the pentose phosphate and Warburg effect pathways. The lipid profile of patients who experienced unfavourable outcomes revealed a higher heterogeneity in the abundance of lipids and fewer associations between markers in contrast to the favourable outcome group. Our findings indicate that changes in salivary and plasma metabolites in GBM patients can potentially be employed as less invasive prognostic biomarkers/biomarker panel but validation with larger cohorts is required. Saliva and plasma samples were collected from 21 newly diagnosed GBM patients pre and post‐operatively. Metabolomic and lipidomic profiles were analysed using LC‐QqQ‐MS and LC‐QTOF‐MS. GBM patients were classified as favourable or unfavourable patients according to clinical outcomes (progression‐free survival (PFS) >nine months or PFS ≤nine months, respectively). The data were investigated using univariate and multivariate statistical analyses and graphical LASSO‐based graphic network analyses.
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期刊: Oncotarget
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