2011 - Transplantomics and Biomarkers in Transplantation

Abstract Driven Session

9.3 - Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-organ Transplant Rejection and Other Conditions

Presenter: Rong, Chen, Stanford, CA, USA
Authors: Rong Chen, Tara Sigdel, Li Li, Neeraja Kambham, Joel Dudley, Alexander Morgan, Hannah Valantine, Kiran Khush, Minnie Sarwal, Atul Butte

Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-organ Transplant Rejection and Other Conditions

Rong Chen1,4, Tara Sigdel1,4, Li Li1,4, Neeraja Kambham3, Joel Dudley1,4, Alexander Morgan1,4, Hannah Valantine2, Kiran Khush2, Minnie Sarwal1,4, Atul Butte1,4.
1Department of Pediatrics, 2Division of Cardiovascular Medicine, and 3Department of Pathology, Stanford University; 4Lucile Packard Children’s Hospital; Stanford, CA, USA.

Serum proteins are routinely used to diagnose diseases, but are hard to find due to low sensitivity in screening the serum proteome. Public repositories of microarray data, such as the Gene Expression Omnibus (GEO), contain RNA expression profiles for over 16,000 biological conditions, covering more than 30% of US mortality. We hypothesized that genes coding for serum- and urine-detectable proteins and showing differential expression of RNA in disease-damaged tissues, would make ideal diagnostic protein biomarkers for those diseases. We showed that predicted protein biomarkers are significantly enriched for known diagnostic protein biomarkers in 22 diseases, with enrichment significantly higher in diseases for which at least three datasets are available. We then used this strategy to search for new biomarkers indicating acute rejection (AR) across different types of transplanted solid organs. We integrated three biopsy-based microarray studies of AR from pediatric renal, adult renal and adult cardiac transplantation and identified 45 genes upregulated in all three. From this set, we chose 10 proteins for serum ELISA assays in 39 renal transplant patients, and discovered three that were significantly higher in AR.Interestingly, all three proteins were also significantly higher during AR in the 63 cardiac transplant recipients studied. Our best marker, serum PECAM1, identified renal AR with 89% sensitivity and 75% specificity, and also showed increased expression in AR by immunohistochemistry in renal, hepatic and cardiac transplant biopsies. Our results demonstrate that integrating gene expression microarray measurements from disease samples and even publicly-available data sets can be a powerful, fast, and cost-effective strategy for the discovery of new diagnostic serum protein biomarkers.

Important Disclaimer

By viewing the material on this site you understand and accept that:

  1. The opinions and statements expressed on this site reflect the views of the author or authors and do not necessarily reflect those of The Transplantation Society and/or its Sections.
  2. The hosting of material on The Transplantation Society site does not signify endorsement of this material by The Transplantation Society and/or its Sections.
  3. The material is solely for educational purposes for qualified health care professionals.
  4. The Transplantation Society and/or its Sections are not liable for any decision made or action taken based on the information contained in the material on this site.
  5. The information cannot be used as a substitute for professional care.
  6. The information does not represent a standard of care.
  7. No physician-patient relationship is being established.



Staff Directory


The Transplantation Society
International Headquarters
505 Boulevard René-Lévesque Ouest
Suite 1401
Montréal, QC, H2Z 1Y7