Changes in gene expression profiles were investigated in 23 patients with Niemann–Pick C1 disease (NPC). cDNA expression microarrays with subsequent validation by qRT-PCR were used. Comparison of NPC to control samples revealed upregulation of genes involved in inflammation (MMP3, THBS4), cytokine signalling (MMP3), extracellular matrix degradation (MMP3, CTSK), autophagy and apoptosis (CTSK, GPNMB, PTGIS), immune response (AKR1C3, RCAN2, PTGIS) and processes of neuronal development (RCAN2). Downregulated genes were associated with cytoskeletal signalling (ACTG2, CNN1); inflammation and oxidative stress (CNN1); inhibition of cell proliferation, migration and differentiation; ERK-MAPK pathway (COL4A1, COL4A2, CPA4); cell adhesion (IGFBP7); autophagy and apoptosis (CDH2, IGFBP7, COL4A2); neuronal function and development (CSRP1); and extracellular matrix stability (PLOD2). When comparing NPC and Gaucher patients together versus controls, upregulation of SERPINB2 and IL13RA2 and downregulation of CSRP1 and CNN1 were characteristic. Notably, in NPC patients, the expression of PTGIS is upregulated while the expression of PLOD2 is downregulated when compared to Gaucher patients or controls and potentially could serve to differentiate these patients. Interestingly, in NPC patients with (i) jaundice, splenomegaly and cognitive impairment/psychomotor delay—the expression of ACTG2 was especially downregulated; (ii) ataxia—the expression of ACTG2 and IGFBP5 was especially downregulated; and (iii) VSGP, dysarthria, dysphagia and epilepsy—the expression of AKR1C3 was especially upregulated while the expression of ACTG2 was downregulated. These results indicate disordered apoptosis, autophagy and cytoskeleton remodelling as well as upregulation of immune response and inflammation to play an important role in the pathogenesis of NPC in humans.

中文翻译：

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全球基因表达的变化表明，尼曼-匹克C病患者的自噬，细胞凋亡和炎性过程紊乱以及细胞骨架信号转导和神经元发育的下调。

研究了23名Niemann–Pick C1病（NPC）患者的基因表达谱变化。使用通过qRT-PCR随后验证的cDNA表达微阵列。NPC与对照样品的比较显示涉及炎症（MMP3，THBS4），细胞因子信号（MMP3），细胞外基质降解（MMP3，CTSK），自噬和细胞凋亡（CTSK，GPNMB，PTGIS），免疫反应（AKR1C3，RCAN2，PTGIS）和神经元发育过程（RCAN2）。下调的基因与细胞骨架信号转导（ACTG2，CNN1）有关。炎症和氧化应激（CNN1）；抑制细胞增殖，迁移和分化；ERK-MAPK途径（COL4A1，COL4A2，CPA4）；细胞粘附（IGFBP7）；自噬和细胞凋亡（CDH2，IGFBP7，COL4A2）; 神经元功能与发育（CSRP1）；和细胞外基质稳定性（PLOD2）。将NPC和Gaucher患者与对照组进行比较时，SERPINB2和IL13RA2的上调并且CSRP1和CNN1的下调是特征。值得注意的是，在鼻咽癌患者，表达PTGIS的同时表达上调PLOD2相比戈谢病患者或控制何时和潜在可有助于区分这些患者中下调。有趣的是，在（i）黄疸，脾肿大和认知障碍/精神运动迟缓的NPC患者中，ACTG2的表达特别下调；（ii）共济失调-ACTG2和IGFBP5的表达特别下调；（iii）VSGP，构音障碍，吞咽困难和癫痫病-AKR1C3的表达当ACTG2的表达下调时，其特别是上调。这些结果表明细胞凋亡紊乱，自噬和细胞骨架重塑以及免疫应答和炎症的上调在人鼻咽癌的发病中起重要作用。