关键词: AIR, acute inflammatory response ALK, anaplastic lymphoma kinase ANG, angiogenesis APR, acute phase reaction BRCA1/2, Breast Cancer Gene 1, Breast Cancer Gene 2 Biological scores Biomarker CA, complement activation CI, confidence interval CPH, Cox proportional hazards CV, coefficient of variation ECM, extracellular matrix organization EGFR, epidermal growth factor receptor FDA, US Food and Drug Administration GLY, glycolysis HR, hazard ratio HbA1c, hemoglobin A1c IFN1, interferon type 1 signaling and response IFNg, Interferon γ signaling and response IRn, type n immune response IT, immune tolerance LC MS-MS, liquid chromatography with tandem mass spectrometry MALDI ToF, matrix-assisted laser desorption/ionization time of flight MRM, multiple reaction monitoring MS, mass spectral Mass spectrometry NSCLC, non-small cell lung cancer OS, overall survival PC, principal component PCA, principal component analysis PCn, principal component n PD-1, programmed cell death protein 1 PD-L1, programmed death-ligand 1 Proteomics QC, quality control Serum proteome Set enrichment analysis WH, wound healing m/Z, mass/charge

来  源:   DOI:10.1016/j.clinms.2020.09.001   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
UNASSIGNED: Most diseases involve a complex interplay between multiple biological processes at the cellular, tissue, organ, and systemic levels. Clinical tests and biomarkers based on the measurement of a single or few analytes may not be able to capture the complexity of a patient\'s disease. Novel approaches for comprehensively assessing biological processes from easily obtained samples could help in the monitoring, treatment, and understanding of many conditions.
UNASSIGNED: We propose a method of creating scores associated with specific biological processes from mass spectral analysis of serum samples.
UNASSIGNED: A score for a process of interest is created by: (i) identifying mass spectral features associated with the process using set enrichment analysis methods, and (ii) combining these features into a score using a principal component analysis-based approach. We investigate the creation of scores using cohorts of patients with non-small cell lung cancer, melanoma, and ovarian cancer. Since the circulating proteome is amenable to the study of immune responses, which play a critical role in cancer development and progression, we focus on functions related to the host response to disease.
UNASSIGNED: We demonstrate the feasibility of generating scores, their reproducibility, and their associations with clinical outcomes. Once the scores are constructed, only 3 µL of serum is required for the assessment of multiple biological functions from the circulating proteome.
UNASSIGNED: These mass spectrometry-based scores could be useful for future multivariate biomarker or test development studies for informing treatment, disease monitoring and improving understanding of the roles of various biological functions in multiple disease settings.
摘要:
大多数疾病涉及细胞的多个生物过程之间复杂的相互作用,组织,器官,和系统水平。基于单一或少数分析物测量的临床测试和生物标志物可能无法捕获患者疾病的复杂性。从容易获得的样品中全面评估生物过程的新方法可能有助于监测,治疗,对许多条件的理解。
我们提出了一种从血清样品的质谱分析中创建与特定生物过程相关的分数的方法。
通过以下方式创建感兴趣的过程的得分:(i)使用集合富集分析方法识别与该过程相关的质谱特征,和(ii)使用基于主成分分析的方法将这些特征组合为分数。我们使用非小细胞肺癌患者的队列研究评分的创建,黑色素瘤,和卵巢癌。由于循环蛋白质组适合于免疫反应的研究,它们在癌症的发展和进展中起着至关重要的作用,我们关注与宿主对疾病的反应相关的功能。
我们证明了生成分数的可行性,它们的再现性,以及它们与临床结果的关联。一旦分数被构建,从循环蛋白质组中评估多种生物学功能仅需要3µL血清。
这些基于质谱的评分可用于未来的多变量生物标志物或测试开发研究,以告知治疗,疾病监测和提高对多种疾病环境中各种生物功能作用的理解。
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