대한신장학회

논문분류	춘계학술대회 초록집
제목	Discovery and validation of urinary mRNA signatures for non-invasive diagnosis of acute rejection
저자	Jungwoo Seo1, Yu-Ho Lee1, Seon Hwa Park1, Ju-Young Moon1, Kyung Hwan Jeong1, Chan-Duck Kim2, Byung Ha Chung3, Jae Berm Park4, Yeong Hoon Kim5, Sang-Ho Lee1
출판정보	2018; 2018(1):
키워드	Acute rejection \| Kidney transplantation \| Urinary mRNA \| Meta-analysis
초록	Objectives: In the field of mRNA biomarker research, urine samples have considered a good source to monitor allograft status, because urinary cells contain various molecules mirrored in ongoing kidney injury or allograft status as well as could be easily sampled and truly non-invasive biomaterial in clinical setting. Since this reason, urine samples in many studies have been used for monitoring acute rejection and immune status. Methods: Meta-analysis was conducted with microarray data on acute rejection of kidney biopsy from the public genomics data repositories Gene Expression Omnibus (GEO). We assigned 315 urine samples into 98 training and 217 validation sets to develop the diagnostic signatures for diagnosis of AR. The expression levels of transcripts were determined in urinary cells using the comparative PCR method. Results: Nine genes were identified to discriminate AR from STA by meta-analysis. We confirmed that the levels of six mRNAs (C1QB, CD3ε, CXCL9, IP-10, PSMB9, and Tim-3) were significantly increased in acute rejection by the comparative PCR assay and developed three models to predict AR by various combinations with six genes. We also validated six genes and the models for diagnosing acute rejection in independent samples. The models yielded the AUC values from 0.78 (95% CI, 0.68-0.87; P<0.0001) to 0.80 (95% CI, 0.71-0.89; P<0.0001) by ROC curve analysis. Furthermore, we assessed performance of each signature through decision curve analysis for clinical benefit. Conclusions: We performed meta-analysis to discovery novel biomarkers for the diagnosis of AR and developed three different signatures using six mRNAs elevated in patients with AR. Furthermore, we demonstrated that each signature of urinary mRNA expression can certainly be helpful to monitor the activation of intra-graft immune injury as a noninvasive diagnosis. Further, it is necessary to evaluate three models in lager cohort for potentially predicting acute rejection and managing patients with an appropriate degree of immunosuppressive therapy.
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