Gene expression profiling-based identification of CD28 and PI3K as new biomarkers for chronic graft-versus-host disease.

Abstract

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.

• Authors: Peilong Lai, Jianyu Weng, Zesheng Lu, Rong Guo, Chenwei Luo, Suijing Wu, Wei Ling, Suxia Geng, Xin Du
• Journal: DNA and cell biology (DNA Cell Biol) Vol. 30 Issue 12 Pg. 1019-25 (Dec 2011) ISSN: 1557-7430 [Electronic] United States
• PMID: 21682596 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• CD28 Antigens
• Phosphatidylinositol 3-Kinases

Topics

• Adult
• Biomarkers
• CD28 Antigens (biosynthesis, blood, genetics)
• Chronic Disease
• Disease Progression
• Female
• Flow Cytometry
• Gene Expression Profiling (methods)
• Graft vs Host Disease (blood, genetics)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Leukemia, Myeloid, Acute (surgery)
• Leukocytes, Mononuclear (metabolism)
• Male
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Phosphatidylinositol 3-Kinases (biosynthesis, blood, genetics)
• Real-Time Polymerase Chain Reaction
• Risk
• T-Lymphocyte Subsets (metabolism)
• Transplantation, Homologous (adverse effects)
• Up-Regulation
• Young Adult