Identification of urinary soluble E-cadherin as a novel biomarker for diabetic nephropathy.
BACKGROUND
Currently, early diagnosis of diabetic nephropathy (DN) remains a major challenge. Thus, more investigations into new DN-related biomarkers are needed.


METHODS
We employed urinary proteomic approach of fluorescence-based difference gel electrophoresis (DIGE) and mass spectrometry to identify novel biomarkers in urine samples, which were from type 2 diabetes patients with normoalbuminuria (DM group), microalbuminuria (DN1 group), macroalbuminuria (DN2 group) and control group (n=8 in each group). The identified biomarker was further studied by western blot in urine samples (n=6 in each group) and immunohistochemistry in renal biopsies. Besides, the urinary level of biomarker was detected and analyzed using enzyme-linked immunosorbent assay(ELISA) method (n=40 in each group).


RESULTS
A novel DN-related biomarker, urinary E-cadherin, was identified by proteomic methods, which up-regulated 1.3-fold, 5.2-fold and 8.5-fold in DM, DN1 and DN2 groups compared with control group. Meanwhile, high expression of urinary soluble 80 kDa fragment of E-cadherin (sE-cadherin) was verified in DN groups by western blot. The ELISA data also demonstrated that urinary sE-cadherin-to-creatinine ratio was significantly increased in DN1 and DN2 groups versus DM group or control group (2751.5+/-164 and 5839.6+/-428 vs 721.9+/-93 or 652.7+/-87 microg/g; p<0.001). The sensitivity and specificity of urinary sE-cadherin for diagnosis of DN were calculated as 78.8% (95% CI, 74-83%) and 80% (95% CI, 65-91%). Besides, immunohistochemical stain showed that E-cadherin expression was markedly decreased in renal tubular epithelial cells of patients with DN versus healthy controls.


CONCLUSIONS
Urinary sE-cadherin has a potential clinical diagnostic value for DN and E-cadherin may participate in the pathogenesis of DN.
Jiang
Hongjuan
H
Department of Nephrology, The Second Hospital of Shandong University, 247 Beiyuan Road, Jinan, Shandong, PR China.
Guan
Guangju
G
Zhang
Rui
R
Liu
Gang
G
Cheng
Jing
J
Hou
Xianghua
X
Cui
Yazhou
Y
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000652:urine*; D015153:Blotting, Western; D015820:Cadherins / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000652:urine*; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D012680:Sensitivity and Specificity; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015415:Biomarkers; D015820:Cadherins