Lysosome and Cytoskeleton Pathways Are Robustly Enriched in the Blood of Septic Patients: A Meta-Analysis of Transcriptomic Data.
Lysosome and Cytoskeleton Pathways Are Robustly Enriched in the Blood of Septic Patients: A Meta-Analysis of Transcriptomic Data.
复制标题
溶酶体和细胞骨架途径在化脓性患者的血液中富含：转录组数据的荟萃分析。
DOI：
10.1155/2015/984825
复制
发表时间：
2015
影响因子：
4.6
通讯作者：
Gao L
中科院分区：
文献类型：
--
作者：
Ma J;Chen C;Barth AS;Cheadle C;Guan X;Gao L
背景资料。脓毒症是全世界重症监护病房死亡的主要原因。更好地了解血液系统对脓毒症的反应应该加快识别生物标记物，以便进行早期诊断和治疗干预。方法：研究方法。我们分析了微阵列研究，其数据可从GEO资料库获得，并对脓毒症患者和正常对照组的全血进行了研究。结果。我们确定了由450个个体组成的6个队列(脓毒症=323，对照=127)，提供了全基因组信使RNA(MRNA)的表达数据。通过荟萃分析，我们发现在人类败血症患者中，除了已知的信号通路(包括MAPK、TLR)外，“溶酶体”和“细胞骨架”通路相对于对照组上调。溶酶体途径中的关键调控基因包括溶酶体酸性水解酶(如组织蛋白酶A、D)以及主要的膜蛋白(LAMP1、2)和次要的膜蛋白(SORT1、LAPTM4B)。相反，与“核糖体”、“剪接体”和“细胞黏附分子”相关的途径被发现下调，以及已知的免疫功能障碍途径。总体而言，我们的研究揭示了人类脓毒症血液中不同的mRNA激活谱和蛋白质-蛋白质相互作用网络。结论。我们的研究结果表明，溶酶体和细胞骨架途径中的mRNA异常表达可能在人类脓毒症的分子病理生物学中起着关键作用。
Background. Sepsis is a leading cause of mortality in intensive care units worldwide. A better understanding of the blood systems response to sepsis should expedite the identification of biomarkers for early diagnosis and therapeutic interventions. Methods. We analyzed microarray studies whose data is available from the GEO repository and which were performed on the whole blood of septic patients and normal controls. Results. We identified 6 cohorts consisting of 450 individuals (sepsis = 323, control = 127) providing genome-wide messenger RNA (mRNA) expression data. Through meta-analysis we found the “Lysosome” and “Cytoskeleton” pathways were upregulated in human sepsis patients relative to controls, in addition to previously known signaling pathways (including MAPK, TLR). The key regulatory genes in the “Lysosome” pathway include lysosomal acid hydrolases (e.g., protease cathepsin A, D) as well as the major (LAMP1, 2) and minor (SORT1, LAPTM4B) membrane proteins. In contrast, pathways related to “Ribosome”, “Spliceosome” and “Cell adhesion molecules” were found to be downregulated, along with known pathways for immune dysfunction. Overall, our study revealed distinct mRNA activation profiles and protein-protein interaction networks in blood of human sepsis. Conclusions. Our findings suggest that aberrant mRNA expression in the lysosome and cytoskeleton pathways may play a pivotal role in the molecular pathobiology of human sepsis.
登录
查看更多内容
影响因子：
3.7
作者：
Castoldi A;Braga TT;Correa-Costa M;Aguiar CF;Bassi ÊJ;Correa-Silva R;Elias RM;Salvador F;Moraes-Vieira PM;Cenedeze MA;Reis MA;Hiyane MI;Pacheco-Silva Á;Gonçalves GM;Saraiva Câmara NO
通讯作者：
Saraiva Câmara NO
DOI：
10.1186/cc10359
发表时间：
2011
期刊：
Critical care (London, England)
影响因子：
--
作者：
de Montmollin E;Annane D
通讯作者：
Annane D
影响因子：
2.8
作者：
de Guadiana Romualdo, Luis Garcia;Esteban Torrella, Patricia;Albaladejo Oton, Maria Dolores
通讯作者：
Albaladejo Oton, Maria Dolores
影响因子：
14.2
作者：
Gao, Li;Grant, Audrey V.;Barnes, Kathleen C.
通讯作者：
Barnes, Kathleen C.
影响因子：
4.4
作者：
Barth, Andreas S.;Kumordzie, Ami;Tomaselli, Gordon F.
通讯作者：
Tomaselli, Gordon F.