Urinary Proteomics Evaluation in Interstitial Cystitis/Painful Bladder Syndrome: A Pilot Study
INTERNATIONAL BRAZ J UROL
Authors: Goo, Young Ah; Tsai, Yihsuan S.; Liu, Alvin Y.; Goodlett, David R.; Yang, Claire C.
Abstract
Purpose: Interstitial cystitis/painful bladder syndrome (IC/PBS) is characterized by chronic pain, pressure and discomfort felt in the pelvis or bladder. An in-depth shotgun proteomics study was carried out to profile the urinary proteome of women with IC/PBS to identify possible specific proteins and networks associated with IC/PBS. Materials and Methods: Urine samples from ten female IC/PBS patients and ten female asymptomatic, healthy control subjects were analyzed in quadruplicate by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on a hybrid linear ion trap-orbitrap mass spectrometer. Gas-phase fractionation (GPF) was used to enhance protein identification. Differences in protein quantity were determined by peptide spectral counting. Results: alpha-1B-glycoprotein (A1BG) and orosomucoid-1 (ORM1) were detected in all IC/PBS patients, and 60% of these patients had elevated expression of these two proteins compared to control subjects. Transthyretin (TTR) and hemopexin (HPX) were detected in all control individuals, but >= 60% of the IC/PBS patients had decreased expression levels of these two proteins. Enrichment functional analysis showed cell adhesion and response to stimuli were down-regulated whereas response to inflammation, wounding, and tissue degradation were up-regulated in IC/PBS. Activation of neurophysiological processes in synaptic inhibition, and lack of DNA damage repair may also be key components of IC/PBS. Conclusion: There are qualitative and quantitative differences between the urinary proteomes of women with and without IC/PBS. We identified a number of proteins as well as pathways/networks that might contribute to the pathology of IC/PBS or result from perturbations induced by this condition.
Integrative Proteomics and Tissue Microarray Profiling Indicate the Association between Overexpressed Serum Proteins and Non-Small Cell Lung Cancer
PLOS ONE
Authors: Liu, Yansheng; Luo, Xiaoyang; Hu, Haichuan; Wang, Rui; Sun, Yihua; Zeng, Rong; Chen, Haiquan
Abstract
Lung cancer is the leading cause of cancer deaths worldwide. Clinically, the treatment of non-small cell lung cancer (NSCLC) can be improved by the early detection and risk screening among population. To meet this need, here we describe the application of extensive peptide level fractionation coupled with label free quantitative proteomics for the discovery of potential serum biomarkers for lung cancer, and the usage of Tissue microarray analysis (TMA) and Multiple reaction monitoring (MRM) assays for the following up validations in the verification phase. Using these state-of-art, currently available clinical proteomic approaches, in the discovery phase we confidently identified 647 serum proteins, and 101 proteins showed a statistically significant association with NSCLC in our 18 discovery samples. This serum proteomic dataset allowed us to discern the differential patterns and abnormal biological processes in the lung cancer blood. Of these proteins, Alpha-1B-glycoprotein (A1BG) and Leucine-rich alpha-2-glycoprotein (LRG1), two plasma glycoproteins with previously unknown function were selected as examples for which TMA and MRM verification were performed in a large sample set consisting about 100 patients. We revealed that A1BG and LRG1 were overexpressed in both the blood level and tumor sections, which can be referred to separate lung cancer patients from healthy cases.