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An age-independent gene signature for monitoring acute rejection in kidney transplantation.

Publication ,  Journal Article
Shaw, BI; Cheng, DK; Acharya, CR; Ettenger, RB; Lyerly, HK; Cheng, Q; Kirk, AD; Chambers, ET
Published in: Theranostics
2020

Acute rejection (AR) remains a significant problem that negatively impacts long-term renal allograft survival. Numerous therapies are used to prevent AR that differ by center and recipient age. This variability confounds diagnostic methods. Methods: To develop an age-independent gene signature for AR effective across a broad array of immunosuppressive regimens, we compiled kidney transplant biopsy (n=1091) and peripheral blood (n=392) gene expression profiles from 12 independent public datasets. After removing genes differentially expressed in pediatric and adult patients, we compared gene expression profiles from biopsy and peripheral blood samples of patients with AR to those who were stable (STA), using Mann-Whitney U Tests with validation in independent testing datasets. We confirmed this signature in pediatric and adult patients (42 AR and 47 STA) from our institutional biorepository. Results: We identified a novel age-independent gene network that identified AR from both kidney and blood samples. We developed a 90-probe set signature targeting 76 genes that differentiated AR from STA and found an 8 gene subset (DIP2C, ENOSF1, FBXO21, KCTD6, PDXDC1, REXO2, HLA-E, and RAB31) that was associated with AR. Conclusion: We used publicly available datasets to create a gene signature of AR that identified AR irrespective of immunosuppression regimen or recipient age. This study highlights a novel model to screen and validate biomarkers across multiple treatment regimens.

Duke Scholars

Published In

Theranostics

DOI

EISSN

1838-7640

Publication Date

2020

Volume

10

Issue

15

Start / End Page

6977 / 6986

Location

Australia

Related Subject Headings

  • Young Adult
  • Transplantation, Homologous
  • Transcriptome
  • ROC Curve
  • Middle Aged
  • Male
  • Kidney Transplantation
  • Infant
  • Humans
  • Graft Rejection
 

Citation

APA
Chicago
ICMJE
MLA
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Shaw, B. I., Cheng, D. K., Acharya, C. R., Ettenger, R. B., Lyerly, H. K., Cheng, Q., … Chambers, E. T. (2020). An age-independent gene signature for monitoring acute rejection in kidney transplantation. Theranostics, 10(15), 6977–6986. https://doi.org/10.7150/thno.42110
Shaw, Brian I., Daniel K. Cheng, Chaitanya R. Acharya, Robert B. Ettenger, Herbert Kim Lyerly, Qing Cheng, Allan D. Kirk, and Eileen T. Chambers. “An age-independent gene signature for monitoring acute rejection in kidney transplantation.Theranostics 10, no. 15 (2020): 6977–86. https://doi.org/10.7150/thno.42110.
Shaw BI, Cheng DK, Acharya CR, Ettenger RB, Lyerly HK, Cheng Q, et al. An age-independent gene signature for monitoring acute rejection in kidney transplantation. Theranostics. 2020;10(15):6977–86.
Shaw, Brian I., et al. “An age-independent gene signature for monitoring acute rejection in kidney transplantation.Theranostics, vol. 10, no. 15, 2020, pp. 6977–86. Pubmed, doi:10.7150/thno.42110.
Shaw BI, Cheng DK, Acharya CR, Ettenger RB, Lyerly HK, Cheng Q, Kirk AD, Chambers ET. An age-independent gene signature for monitoring acute rejection in kidney transplantation. Theranostics. 2020;10(15):6977–6986.

Published In

Theranostics

DOI

EISSN

1838-7640

Publication Date

2020

Volume

10

Issue

15

Start / End Page

6977 / 6986

Location

Australia

Related Subject Headings

  • Young Adult
  • Transplantation, Homologous
  • Transcriptome
  • ROC Curve
  • Middle Aged
  • Male
  • Kidney Transplantation
  • Infant
  • Humans
  • Graft Rejection