ESPN 54th Annual Meeting

ESPN 2022


 
Candidate Biomarker(s) for Cystinosis With Omic-based Technology: From Laboratory to Bed-side
EMIRHAN NEMUTLU 1 CEMIL CAN EYLEM 1 BORA GÜLHAN 2 IPEK BAYSAL 3 SAMİYE YABANOGLU-CİFTCİ 4 SEDEF KIR 1 KEZBAN ULUBAYRAM 5 GÜLBERK UÇAR 4 OSMAN UĞUR SEZERMAN 6 FATİH OZALTİN 2 REZAN TOPALOGLU 2

1- HACETTEPE UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF ANALYTICAL CHEMISTRY, ANKARA, TURKEY
2- HACETTEPE UNIVERSITY FACULTY OF MEDICINE, DEPARTMENT OF PEDIATRICS, DIVISION OF PEDIATRIC NEPHROLOGY, ANKARA, TURKEY
3- HACETTEPE UNIVERSITY VOCATIONAL SCHOOL OF HEALTH SERVICES, ANKARA, TURKEY
4- HACETTEPE UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ANKARA, TURKEY
5- HACETTEPE UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, ANKARA, TURKEY
6- ACIBADEM MEHMET ALI AYDINLAR UNIVERSITY FACULTY OF MEDICINE, DEPARTMENT OF BIOSTATISTICS AND MEDICAL INFORMATICS, ISTANBUL, TURKEY
 
Introduction:

Cystinosis is a rare autosomal recessive lysosomal cystine storage disease that stems from defective cystinosin protein caused by mutations in CTNS. The most frequently applied diagnostic method is the confirmation of the increased leukocyte cystine levels. However, this test is expensive, unreproducible and difficult to have an access in everywhere. This study aimed to investigate new biomarkers for the diagnosis and follow-up of this rare disease with multiomics (genomic, proteomic and metabolomic) methods.

Material and methods:

 Multiomic studies have been performed in plasma and urine samples from three pediatric groups;  a) newly-diagnosed cystinosis patients (n=14), b) cystinosis patients under treatment (n=31), c) healthy controls (n=30) and in d) siRNA based cystinosis model in vitro.

Results:

Multivariate analysis revealed different plasma and urinary profile between groups. The candidate biomarkers were determined using receiver operating curve (ROC) analysis. Among these metabolites; L-serine, taurine, 4-Trimethylammoniobutanoic acid, glutathione, PE(O-18:1(9Z)/0:0), 2-hydroxyphenyl acetic acid, and 3-indoxyl sulphate in plasma and  allo-inositol, oleanonic acid,4-hydroxyphenylpyruvic acid, 2-hydroxybutiric acid, cystine, pyruvic acid, valine, phenylalanine, N-acetyl-L-glutamic acid, 3-aminopropionitrile, ribitol, hydroquinone, glucuronic acid, 3-phosphoglycerate, xanthine, creatinine and 5-aminovaleric acid in urine samples were found as candidate biomarkers in for the differentiation of patients with cystinosis from  healthy individuals. Besides, for the first time in the literature, siRNA based CTNS silenced HK2 cells were generated as an in vitro disease model to determine omics differences compared to wild type HK-2 cells to understand metabolic alterations caused by cystinosin deficiency at cellular level.

Conclusions:

Our study led to the description of candidate biomarkers and important results, which would pave the way for a better understanding of the pathophysiology of cystinosis.