Proteomic Analyses of Autologous Chondrocyte Implantation Plasma Highlight Cartilage Acidic Protein 1 as a Candidate for Preclinical Screening.
Proteomic Analyses of Autologous Chondrocyte Implantation Plasma Highlight Cartilage Acidic Protein 1 as a Candidate for Preclinical Screening.
复制标题
DOI：
10.1177/03635465231156616
复制
发表时间：
2023-05
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
分层是必要的，以确保只有可能受益的患者接受自体软骨细胞植入（ACI）。识别血液中可测量的生物标志物来预测ACI结果将是有利的，从而避免了侵入性滑液采集的需要。评估蛋白质组学分析是否可以用于识别对ACI反应良好或不良的个体的新的候选血液生物标志物。对照实验室研究。采用等压标记相对和绝对定量（iTRAQ）质谱法评估ACI应答者（ACI后Lysholm平均改善33，n = 10）或无应答者（平均- 13，n = 10）血浆中的蛋白质组，这些血浆收集于软骨摘取手术（第1期）或培养扩大的软骨细胞植入（第2期）时。另一种蛋白质组学方法，无标记定量液相色谱-串联质谱法，用于单独分析血浆样品（大多数与iTRAQ匹配）。从两个蛋白质组学数据集中分析差异丰富的蛋白质（±2.0倍），并通过单个样品的免疫分析验证通过合并iTRAQ鉴定的感兴趣标记。iTRAQ蛋白组学检测术前ACI反应者与无反应者血浆蛋白差异（16个蛋白，≥±2.0倍变化，P < 0.05）。最明显的血浆蛋白质组变化是在对ACI无反应的1期手术的反应中明显的，有48种蛋白质在手术之间的差异丰富。无标记定量液相色谱-串联质谱分析这些相同的血浆样品（非混合）导致很少的蛋白质被鉴定出显着差异丰富。然而，这项工作强调，与应答者相比，术前无应答者的软骨酸性蛋白1增加。这项研究首次使用蛋白质组学技术来分析ACI患者的血浆。尽管iTRAQ分析表明ACI反应者和无反应者的血浆蛋白质组存在差异，但当使用替代的非聚合技术进行评估时，这些发现并未得到重复。这项研究强调了在试图鉴定新的生物标志物时分析血浆蛋白质组的一些困难。无论如何，软骨酸性蛋白1已被确定为候选蛋白，可在血浆中检测到，并可在治疗前预测ACI的预后。本研究确定的候选血浆蛋白生物标志物有可能帮助确定哪些患者最适合ACI治疗。
Stratification is required to ensure that only patients likely to benefit receive autologous chondrocyte implantation (ACI). It would be advantageous to identify biomarkers to predict ACI outcome that are measurable in blood, avoiding the need for an invasive synovial fluid harvest. To assess if proteomic analyses can be used to identify novel candidate blood biomarkers in individuals who respond well or poorly to ACI. Controlled laboratory study. Isobaric tagging for relative and absolute quantitation (iTRAQ) mass spectrometry was used to assess the proteome in plasma pooled from ACI responders (mean Lysholm improvement after ACI, 33; n = 10) or nonresponders (mean, −13; n = 10), collected at the time of surgery for cartilage harvest (stage 1) or implantation of culture-expanded chondrocytes (stage 2). An alternative proteomic method, label-free quantitation liquid chromatography–tandem mass spectrometry, was used to analyze plasma samples (majority matched to iTRAQ) individually. Differentially abundant proteins (±2.0-fold) were analyzed from both proteomic data sets, and markers of interest identified via pooled iTRAQ were validated via immunoassay of individual samples. Protein differences could be detected in the plasma preoperatively between ACI responders and nonresponders (16 proteins; ≥±2.0-fold change; P < .05) using iTRAQ proteomics. The most pronounced plasma proteome shift was evident in response to stage 1 surgery in ACI nonresponders, with 48 proteins being differentially abundant between the procedures. Label-free quantitation liquid chromatography–tandem mass spectrometry analysis of these same plasma samples (nonpooled) resulted in very few proteins being identified that were significantly differentially abundant. However, this work highlighted cartilage acidic protein 1 as being increased preoperatively in nonresponders as compared with responders. This study is the first to use proteomic techniques to profile the plasma of individuals treated with ACI. Despite iTRAQ analysis of pooled plasmas indicating that there are differences in the plasma proteome between responders and nonresponders to ACI, these findings were not replicated when assessed using an alternative nonpooled technique. This study highlights some of the difficulties in profiling the plasma proteome in an attempt to identify novel biomarkers. Regardless, cartilage acidic protein 1 has been identified as a protein candidate, which is detectable in plasma and can predict outcome to ACI before treatment. Candidate plasma protein biomarkers identified in this study have the potential to help determine which patients will be best suited to treatment with ACI.
登录
查看更多内容
影响因子：
4.2
作者：
Harrington GMB;Cool P;Hulme C;Osman A;Chowdhury JR;Kumar N;Budithi S;Wright K
通讯作者：
Wright K
影响因子：
4.2
作者：
Brown, Sharon J.;Harrington, Gabriel M. B.;Wright, Karina T.
通讯作者：
Wright, Karina T.
影响因子：
4.9
作者：
Hulme, Charlotte H.;Wilson, Emma L.;Wright, Karina T.
通讯作者：
Wright, Karina T.
影响因子：
5.6
作者：
Palstrom, Nicolai Bjodstrup;Rasmussen, Lars Melholt;Beck, Hans Christian
通讯作者：
Beck, Hans Christian
影响因子：
29
作者：
Desikan, Rahul S.;Thompson, Wesley K.;Holland, Dominic;Hess, Christopher P.;Brewer, James B.;Zetterberg, Henrik;Blennow, Kaj;Andreassen, Ole A.;McEvoy, Linda K.;Hyman, Bradley T.;Dale, Anders M.
通讯作者：
Dale, Anders M.