Metabolic and proteomic signatures differentiate inflammatory phenotypes from cancer and predict treatment response in patient sera

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Gabriel Cutshaw, Elena V. Demidova, Philip Czyzewicz, Elizabeth Quam, Nicole Lorang, AL Warith AL Siyabi, Surinder Batra, Sanjeevani Arora, Rizia Bardhan
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引用次数: 0

Abstract

Tumors shift their metabolic needs to enable uncontrolled proliferation. Therefore, metabolic assessment of cancer patient sera provides a significant opportunity to noninvasively monitor disease progression and enable mechanistic understanding of the pathways that lead to response. Here, we show Raman spectroscopy (RS), a highly sensitive and label‐free analytical tool, is effective in metabolic profiling across diverse cancer types in patient sera from both pancreatic ductal adenocarcinoma (PDAC) and locally advanced rectal cancer (LARC). We also combine metabolic data with proteomic signatures to predict treatment response. Our data show RS peaks successfully differentiate PDAC patients from healthy controls. Peaks associated with sugars, tyrosine, and DNA/RNA distinguish PDAC patients from chronic pancreatitis, an inflammatory condition that is notoriously difficult to discern from PDAC via current clinical approaches. Furthermore, our study is expanded to investigate response to chemoradiation therapy in LARC patient sera where at pre‐treatment multiple metabolites including glycine, carotenoids, and sugars are jointly correlated to the neoadjuvant rectal (NAR) score indicative of poor prognosis. Via classical univariate AUC–ROC analysis, several RS peaks were found to have an AUC>0.7, highlighting the potential of RS in identifying key metabolites for differentiating complete and poor responders of treatment. Gene set enrichment analysis revealed enrichment of metabolic, immune, and DDR‐related pathways associated with CRT response. Notably, RS‐derived metabolites were significantly correlated with multiple immune signaling proteins and DDR markers, suggesting these distinct analytes converge to reflect systemic changes within the tumor microenvironment. By integrating metabolic, proteomic, and DDR data, we identified pre‐treatment activation of galactose and glycerolipid metabolism, and post‐treatment engagement of cell cycle and p53 signaling pathways. Our findings show that RS, when integrated with complementary protein marker analysis, holds the potential to bridge the translational divide enabling a clinically relevant approach for both diagnosis and predicting response in patient samples.
代谢和蛋白质组学特征区分炎症表型和癌症,并预测患者血清中的治疗反应
肿瘤改变了它们的代谢需求,使不受控制的增殖成为可能。因此,癌症患者血清的代谢评估为无创监测疾病进展提供了重要的机会,并使人们能够对导致反应的途径进行机制理解。在这里,我们展示了拉曼光谱(RS),一种高度敏感且无标签的分析工具,在胰腺导管腺癌(PDAC)和局部晚期直肠癌(LARC)患者血清中不同癌症类型的代谢分析中是有效的。我们还结合代谢数据和蛋白质组学特征来预测治疗反应。我们的数据显示RS峰成功地将PDAC患者与健康对照区分开来。与糖、酪氨酸和DNA/RNA相关的峰值将PDAC患者与慢性胰腺炎区分开来,慢性胰腺炎是一种众所周知的难以通过当前临床方法从PDAC中区分出来的炎症。此外,我们的研究扩展到研究LARC患者血清对放化疗的反应,其中治疗前多种代谢物包括甘氨酸、类胡萝卜素和糖与新辅助直肠(NAR)评分共同相关,表明预后不良。通过经典的单变量AUC-ROC分析,发现几个RS峰的auc值为0.7,突出了RS在鉴别治疗完全反应和不良反应的关键代谢物方面的潜力。基因集富集分析揭示了与CRT反应相关的代谢、免疫和DDR相关途径的富集。值得注意的是,RS衍生的代谢物与多种免疫信号蛋白和DDR标记物显著相关,表明这些不同的分析物融合在一起,反映了肿瘤微环境中的系统性变化。通过整合代谢、蛋白质组学和DDR数据,我们确定了预处理前半乳糖和甘油脂代谢的激活,以及处理后细胞周期和p53信号通路的参与。我们的研究结果表明,当RS与互补蛋白标记分析相结合时,具有弥合翻译鸿沟的潜力,能够为患者样本的诊断和预测反应提供临床相关的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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