Data related to the article "A proteomic approach to identify novel disease biomarkers in LCAT deficiency"

This record contains raw data produced by Centro Cardiologico Monzino related to the article "A proteomic approach to identify novel disease biomarkers in LCAT deficiency" A B S T R A C T<br> Genetic LCAT deficiency is a rare recessive autosomal disease due to loss-of-function mutations in the gene coding for the enzyme lecithin:cholesterol acyltransferase (LCAT). Homozygous carriers are characterized by corneal opacity, haemolytic anaemia and renal disease, which represent the first cause of morbidity and mortality in these subjects. Diagnostic and prognostic markers capable of early detecting declining kidney function in these subjects are not available, and the specific serum or urine proteomic signature of LCAT deficient carriers has never been assessed. Taking advantage of a proteomic approach, we performed 2-DE analysis of carriers' plasma and identified proteins present at different concentration in samples from homozygous carriers. Our data confirm the well-known alterations in the concentration of circulating apolipoproteins, with a statistically significant decrease of both apoA-I and apoA-II and a statistically significant increase of apoC-III. Furthermore, we observed increased level of alpha-1-antitrypsin, zinc-alpha-2-glycoprotein and retinol-binding protein 4, and reduced level of clusterin and haptoglobin. Interestingly, only beta but not alpha subunit of haptoglobin is significant reduced in homozygous subjects.<br> Despite the limited sample size, our findings set the basis for assessing the identified protein in a larger population and for correlating their levels with clinical markers of renal function and anaemia.<br> Significance: This investigation defines the effects of LCAT deficiency on the level of the major plasma proteins in homozygous and heterozygous carriers. Increase for some proteins, with different function, together with a drop for haptoglobin, and specifically for haptoglobin beta chains, are reported for the first time as part of a coherent signature.<br> We are glad to have the opportunity to report our findings on this subject, which is one of the main interests for our research group, when Journal of Proteomics celebrates its 10th anniversary. With its various sections devoted to different areas of research, this journal is a privileged forum for publishing proteomic investigations without restrictions either in sample type or in technical approach. It is as well a privileged forum for reviewing literature data on various topics related to proteomics investigation, as colleagues in our research group have done over the years; by the way, a good share of the reviewed papers were as well reports published in Journal of Proteomics itself. The journal also offers opportunities for focused surveys through thematic issues devoted to a variety of subjects, timely selected for their current relevance in research; it was an honour for colleagues in our group to recently act as editors of one of those. Out of this diverse experience, we express our appreciation for the endeavour of Journal of Proteomics in its first 10 years of life – and wish identical and possibly greater success for the time to come.本数据集包含由蒙奇诺心脏中心（Centro Cardiologico Monzino）产出的原始数据，关联论文《针对LCAT缺乏症识别新型疾病生物标志物的蛋白质组学研究方法》。 摘要 遗传性LCAT缺乏症是一种罕见的常染色体隐性遗传病，由编码卵磷脂胆固醇酰基转移酶（lecithin:cholesterol acyltransferase, LCAT）的基因发生功能丧失型突变所致。纯合突变携带者表现为角膜混浊、溶血性贫血与肾脏疾病，上述症状是该类患者发病与死亡的首要原因。目前尚无能够早期检测该类患者肾功能减退的诊断与预后标志物，且从未有研究评估LCAT缺陷携带者的特异性血清或尿液蛋白质组特征。 本研究借助蛋白质组学方法，对携带者的血浆开展双向凝胶电泳（2-DE）分析，鉴定出纯合突变携带者样本中浓度存在差异的蛋白质。我们的研究证实了循环载脂蛋白浓度的已知异常：载脂蛋白A-I（apoA-I）与载脂蛋白A-II（apoA-II）的浓度均出现具有统计学意义的降低，而载脂蛋白C-III（apoC-III）的浓度则显著升高。此外，我们观察到α1-抗胰蛋白酶、锌α2-糖蛋白以及视黄醇结合蛋白4的水平上升，而簇连蛋白与结合珠蛋白的水平下降。值得注意的是，仅结合珠蛋白的β亚基（而非α亚基）在纯合突变受试者中出现显著降低。 尽管样本量有限，本研究结果为在更大规模人群中验证已鉴定的蛋白质，并将其水平与肾功能、贫血相关临床标志物建立关联奠定了基础。 研究意义 本研究明确了LCAT缺乏症对纯合与杂合突变携带者体内主要血浆蛋白水平的影响。本研究首次报道了多种功能各异的蛋白质水平升高，以及结合珠蛋白（尤其是其β亚基）水平下降的一致性蛋白质组特征。 恰逢《蛋白质组学杂志》（Journal of Proteomics）创刊十周年之际，我们有幸分享本团队在该研究方向的核心成果。该期刊设有覆盖不同研究领域的多个栏目，是不受样本类型与技术方法限制、发表蛋白质组学研究的优质平台。正如本团队成员多年来的实践所示，该期刊同时也是综述蛋白质组学相关领域文献的理想论坛，其中相当一部分综述文章正是发表于《蛋白质组学杂志》自身。此外，该期刊还通过聚焦当前研究热点的专题特刊，为针对性综述提供发表渠道，本团队成员近期就曾担任其中一期特刊的客座编辑。基于上述多元的合作与发表经历，我们对《蛋白质组学杂志》创刊十年以来的付出致以诚挚谢意，并祝愿其未来再创佳绩。