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Proteomic-based research strategy identified laminin subunit alpha 2 as a potential urinary-specific biomarker for the medullary sponge kidney disease
- Source :
- Kidney international. 91(2)
- Publication Year :
- 2016
-
Abstract
- Medullary sponge kidney (MSK) disease, a rare kidney malformation featuring recurrent renal stones and nephrocalcinosis, continues to be diagnosed using expensive and time-consuming clinical/instrumental tests (mainly urography). Currently, no molecular diagnostic biomarkers are available. To identify such we employed a proteomic-based research strategy utilizing urine from 22 patients with MSK and 22 patients affected by idiopathic calcium nephrolithiasis (ICN) as controls. Notably, two patients with ICN presented cysts. In the discovery phase, the urine of 11 MSK and 10 controls, were randomly selected, processed, and analyzed by mass spectrometry. Subsequently, several statistical algorithms were undertaken to select the most discriminative proteins between the two study groups. ELISA, performed on the entire patients' cohort, was used to validate the proteomic results. After an initial statistical analysis, 249 and 396 proteins were identified exclusive for ICN and MSK, respectively. A Volcano plot and ROC analysis, performed to restrict the number of MSK-associated proteins, indicated that 328 and 44 proteins, respectively, were specific for MSK. Interestingly, 119 proteins were found to differentiate patients with cysts (all patients with MSK and the two ICN with renal cysts) from ICN without cysts. Eventually, 16 proteins were found to be common to three statistical methods with laminin subunit alpha 2 (LAMA-2) reaching the higher rank by a Support Vector Machine, a binary classification/prediction scheme. ELISA for LAMA-2 validated proteomic results. Thus, using high-throughput technology, our study identified a candidate MSK biomarker possibly employable in future for the early diagnosis of this disease.
- Subjects :
- 0301 basic medicine
Proteomics
Pathology
Support Vector Machine
030232 urology & nephrology
Bioinformatics
0302 clinical medicine
laminin subunit alpha 2
Tandem Mass Spectrometry
Settore MED/14 - NEFROLOGIA
Cluster Analysis
Kidney
medicine.diagnostic_test
Medicine (all)
Discriminant Analysis
Biomarker
Laminin subunit alpha 2
MSK
Proteomic
Nephrology
medicine.anatomical_structure
Area Under Curve
Biomarker (medicine)
biomarker
Nephrocalcinosis
Algorithms
medicine.medical_specialty
Urinalysis
Urinary system
Enzyme-Linked Immunosorbent Assay
Biology
Medullary sponge kidney
proteomics
03 medical and health sciences
Predictive Value of Tests
medicine
Humans
Medullary Sponge Kidney
Case-control study
Reproducibility of Results
medicine.disease
High-Throughput Screening Assays
body regions
030104 developmental biology
Early Diagnosis
ROC Curve
Case-Control Studies
Laminin
Biomarkers
Subjects
Details
- ISSN :
- 15231755
- Volume :
- 91
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Kidney international
- Accession number :
- edsair.doi.dedup.....8fe7b7f77a5c4267eaa68c2a57fca012