Table 2.

Blood-Based GEP of Messenger RNA and MicroRNA Transcripts

Publication	Study Name	Patient Population & Study Design	Description	Outcome
Messenger RNA
Deng ⁸ , 2006	CARGO	8 U.S. centers, 629 patients, Prospective cohort study	Derivation and validation of GEP	AUC of 0.72 to detect ACR ≥ 3A with GEP score >20, prevalence analysis resulting in 99% NPV using score >30
Pham ⁹ , 2010	IMAGE	13 U.S. centers, 602 patients, Randomized clinical trial	Noninferiority analysis of EMB vs. GEP starting at 6-months	With GEP score <34 to rule out rejection, similar event rates in EMB and GEP groups
Moayedi ²³ , 2019	OAR	35 U.S. centers, 1504 patients, Cross-sectional	Clinical validation with long-term follow-up of patients who underwent GEP surveillance	2% prevalence of ACR both before and after six months post-transplant, 94% 5-year survival
MicroRNA
Duong Van Huyen ²⁴ , 2014		4 French centers, 113 patients, Case-control study	Pre-selected evaluation of 14 miR transcripts by RT-PCR, from both EMB and serum samples	Four miRs were differentially expressed in tissue and serum and validated in ACR and AMR as compared to controls
Dewi ²⁵ , 2017		6 Canadian centers, 63 patients, Case-control study	Pre-selected miRs evaluated by RT-PCR evaluation in serum	Two miRs were associated with ACR, after controlling for immunosuppressive drug levels, kidney function, and C-reactive protein
Constanso-Conde ²⁶ , 2020		1 Spanish center, 66 patients, Prospective Cohort study	Pre-selected evaluation of differential miR expression in ACR by RT-PCR	miR-181a-5p was differentially expressed in ACR ≥ 2R with rise and fall pattern associated with development/treatment of rejection
Shah ²⁷ , 2022	GRAfT	5 U.S. centers, 157 patients, Case-control study	NGS evaluating miR expression	Distinct miR scores between 0–100 were able to distinguish ACR and AMR. Developed and validated for ACR ≥ 2R and pAMR ≥ 1

AUC, area under the curve; ACR, acute cellular rejection; AMR, antibody-mediated rejection; EMB; endomyocardial biopsy; GEP, gene expression profiling; mRNA, messenger RNA; miR, microRNA; NGS, next generation sequencing; NPV, negative predictive value; RT-PCR, reverse transcriptase polymerase chain reaction;