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Graft-versus-Host Disease

Cell cycle and immune-related processes are significantly altered in chronic GVHD

Bone Marrow Transplantation volume 41, pages 1047–1057 (2008)Cite this article

Abstract

Currently, the pathogenesis of chronic GVHD is unclear. To elucidate the molecular characteristics underlying chronic GVHD, we analyzed the gene expression profiles of 21 mononuclear cell samples from allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Self organizing map (SOM) clustering showed that the entire expression profiles of chronic GVHD samples were clearly different from those of the non-GVHD samples, and significance analysis of microarray (SAM) demonstrated that 120 genes, including PTDSS1, VAV1 and CD3D, were up-regulated, and 5 genes, including calnexin, were down-regulated in GVHD patients. Gene ontology annotation revealed that these genes are related to the phosphorous metabolism and lipid biosynthesis. Quantitative real time polymerase chain reaction (qRT-PCR) experiments validated the up-regulation of PTDSS1, VAV1 and CD3D in separate samples. Pathway-wise global test revealed that differential gene expression in cell cycle and T cell immune-associated pathways were significant between GVHD patients and non-GVHD patients. Seventeen classifier genes selected using a PAM (prediction analysis of microarray) algorithm showed favorable performance (prediction accuracy=0.85) for identifying patients with chronic GVHD. In conclusion, we identified differentially expressed genes and pathways in chronic GVHD patients using microarray analysis, and we also selected diagnostic genes predicting chronic GVHD status.

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Acknowledgements

This study was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (0405-BC02-0604-0004).

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Author notes

  1. S J Oh and S B Cho: These authors contributed equally to this work.

Authors and Affiliations

  1. Diagnostic DNA Chip Center, Seoul National University College of Medicine, Seoul, Korea

    S J Oh, S B Cho, S-H Park, C Z Piao, S M Kwon, I Kim, E K Park, J H Kim & S Park

  2. Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

    S J Oh

  3. Seoul National University Biomedical Informatics, Seoul, Korea

    S B Cho & J H Kim

  4. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

    I Kim, S S Yoon, B K Kim & S Park

  5. Department of Internal Medicine, Chung-ang University College of Medicine, Seoul, Korea

    E K Park

  6. Macrogen Inc., Seoul, Korea

    J J Kang & S-J Yang

  7. Digital Genomics Inc., Seoul, Korea

    W J Lee, C-H Yoo, S Hwang & S H Kim

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Correspondence to S Park.

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Supplementary Information accompanies the paper on Bone Marrow Transplantation website (http://www.nature.com/bmt)

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Oh, S., Cho, S., Park, SH. et al. Cell cycle and immune-related processes are significantly altered in chronic GVHD. Bone Marrow Transplant 41, 1047–1057 (2008). https://doi.org/10.1038/bmt.2008.37

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