SERUM PROTEIN PATTERN IN FEMALESTRESS URINARY INCONTINENCE
M. KOCH1, S. SEYFERT2, T. MOHR 3, W. UMEK 4, E. HANZAL5, R. LATERZA 6, H. KOELBL 7, G.MITULOVIC 8;
1Department of Obstetrics andGynecology, Med. Univ. of Vienna, Vienna, Austria, 2ClinicalInstitute of Laboratory Medicine, Med. Univ. of Vienna, Vienna,Austria, 3Sci. Consult Thomas Mohr KG, Guntramsdorf,Austria, 4Obstetrics and Gynecology, Med. Univ. Vienna,Wien, Austria, 5Med. Univ. of Vienna, Vienna, Austria,6Dept of Obstetrics and Gynecology, Med. Univ. Vienna,Vienna, Austria, 7Dept. of Gen. Gynaecology andGynaecologic, Vienna, Austria, 8Med. Univ. of Vienna -KILM, Wien, Austria.
Introduction: Thepathophysiology of Stress Urinary Incontinence (SUI) is poorlyunderstood. In a previous study a significantly different abundanceof six proteins in urine of patients with SUI compared to the urineof continent controls was identified. (1)
Objective: Toidentify a specific proteomic pattern in serum of patients with SUIcompared to the serum of continent controls.
Methods: Serumsamples were collected from 38 patients (19 SUI; 19 matched,continent controls). Sample preparation included serum albumindepletion, in-solution enzymatic digestion of proteins applying acombination of Gluc-C and trypsin and peptide separation using nanoHigh Performance Liquid Chromatography. Label-free quantitation ofpeptides and proteins was performed after triplicate measurementsusing quadrupole time-of-flight mass spectrometry. Peptideidentification was achieved by searching the Human SwissProt Databaseusing Mascot and X!Tandem. Main outcome measure was the concentrationof each protein in serum. Protein abundance was estimated by usingpeptide counts normalized to counts per million (cpm). Log2-foldchange was estimated based on variance stabilized average log2 cpmvalues using the package edgeR. Resulting p values werecorrected for multiple testing according to Storey et al. A qvalue of <0.25 was considered statistically significant. Proteinswere defined as “not detected” if they were present in <20% ofsamples per group. Proteins were defined as “detected” if theywere present in >80%. If proteins were detected in SUI but notdetected in controls, they were declared as “induced”. Ifproteins were detected in controls, but not in SUI samples, they weredeclared as “depleted”.
Results: A total number of 7012different proteins were identified over all serum samples.Thirty-three proteins were induced (detected in SUI, not in controls)and five proteins were depleted (detected in controls, not in SUI).All five proteins induced in control serum samples are known to playa role in immune response or response to DNA damage. The thirty-threeproteins induced in SUI samples cannot be clustered in specificcategories of function but involve proteins of inflammatory response(proinflammatory/ immunoglobulines), response to cellular stress,coagulation and in a wider sense cytoskeleton stability/ motility.One protein induced in SUI samples, Plasma serine protease inhibitor(SERPINA5), was previously detected to be of significantly higherabundance in urine samples of SUI patients. (1) SERPINA5 is involvedin the regulation of intravascular and extravascular proteolyticactivities and plays hemostatic roles in blood plasma. It acts asprocoagulant and proinflammatory factor by inhibiting theanticoagulant activated protein C factor as well as the generation ofactivated protein C factor. In urine, SERPINA5 inhibits urinary-typeplasminogen activator and kallikrein activities.
Conclusions:Plasma serine protease inhibitor (SERPINA5) was induced in SUI serumsamples. SERPINA5 previously showed a higher abundance in urinesamples of SUI patients (1) and is involved in proteolyticactivities, plays hemostatic roles in plasma and acts as procoagulantas well as proinflammatory factor. Replication of these findings in adifferent population is needed to identify possibleimplications.
References: (1) PMID: 27193112