Department of Haematology, Guangdong General Hospital, Guangzhou, P.R. China.
DNA Cell Biol. 2011 Dec;30(12):1019-25. doi: 10.1089/dna.2011.1284. Epub 2011 Jun 17.
Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently, no reliable biomarkers are available to predict the onset or progression of cGVHD. Therefore, in this study, we collected peripheral blood mononuclear cells from four patients with cGVHD and four ones with non-GVHD after hematopoietic stem cell transplantation and employed Affymetrix GeneChip Human U133 Plus 2.0 microarrays to screen the genes differentially expressed in cGVHD versus non-GVHD groups, with the aim to identify potential clinical biomarkers to predict cGVHD risk or progression. Microarray analysis demonstrated that the expression of 3180 genes changed significantly in cGVHD versus non-GVHD, with 879 genes upregulated and 2301 genes downregulated. Among them we chose CD28 and PI3K as candidates for further verification. Flow cytometry and quantitative real-time polymerase chain reaction analysis confirmed the significant upregulation of CD28 and PI3K in samples from patients with cGVHD compared with patients with non-GVHD, respectively. In conclusion, our study suggested that the upregulation of CD28 and PI3K contributed to the onset and progression of cGVHD and provided evidence that CD28 and PI3K may serve as promising biomarkers for cGVHD.
慢性移植物抗宿主病(cGVHD)是异基因造血干细胞移植后发病率和死亡率的主要原因。目前，尚无可靠的生物标志物可预测 cGVHD 的发病或进展。因此，在这项研究中，我们收集了 4 例 cGVHD 患者和 4 例造血干细胞移植后非-GVHD 患者的外周血单个核细胞，并采用 Affymetrix GeneChip Human U133 Plus 2.0 微阵列筛选 cGVHD 与非-GVHD 组之间差异表达的基因，旨在鉴定潜在的临床生物标志物，以预测 cGVHD 风险或进展。微阵列分析表明，cGVHD 与非-GVHD 相比，有 3180 个基因的表达发生了显著变化，其中 879 个基因上调，2301 个基因下调。其中我们选择 CD28 和 PI3K 作为进一步验证的候选基因。流式细胞术和实时定量聚合酶链反应分析证实，与非-GVHD 患者相比，cGVHD 患者的样本中 CD28 和 PI3K 的表达显著上调。总之，我们的研究表明，CD28 和 PI3K 的上调导致了 cGVHD 的发生和进展，并为 CD28 和 PI3K 可能作为 cGVHD 的有前途的生物标志物提供了证据。
