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Zhang Man - One of the best experts on this subject based on the ideXlab platform.
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Association of serum lipid metabolism with markers of urinary peptides in type 2 diabetes patients
2016Co-Authors: Li Jia, Fu Guangzhen, Wang Junjun, Zhang ManAbstract:Objective: To unveil the differently expressed urinary peptides that are associated with different stages of lipid control for type 2 diabetes mellitus. Methods: Patients with diagnosed type 2 diabetes mellitus (n=58) and normal controls (n=29) were included. Serum and urine samples were collected from these subjects. The fasting plasma glucose (FPG), hemoglobin A1c% (HbA1c), cholesterol (CHOL), triglyceride (TRIG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) were measured by ADVIA2400 Chemistry System. These type 2 diabetic patients were divided into two groups according to CHOL, TRIG, HDL and LDL, respectively. Urinary peptides were condensed by magnetic beads based weak cation exchange chromatography and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ClinProt was used to profile and screen the polypeptide patterns based on different methods of grouping in diabetic patients and normal controls. Nano-liquid chromatography-tandem mass spectrometry was used to identify these urinary peptides. Results: Serum CHOL negatively correlated with urinary peptide m/z 2756.5 (r=-0.315, P=0.016). Serum LDL negatively correlated with urinary peptide m/z 2756.5 (r=-0.390, P=0.002). Areas under the receiver operating characteristic of the three peptides (m/z 2756.5, m/z 3223.2 and m/z 4753.8) were 0.731, 0.673 and 0.602, respectively. The above-mentioned peptide m/z 2756.5 was further identified as fragment of Fibrinogen Alpha Chain precursor and m/z 3223.2 was fragment of prothrombin precursor. Conclusion: There were three urinary peptides (m/z 2756.5, m/z 3223.2 and m/z 4753.8) that differently expressed in different stages of serum lipid control in type 2 diabetes mellitus.National High Technology Research and Development Program of China [2014AA020901]; Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics [Z151100001615060]SCI(E)ARTICLEmzhang99@aliyun.com137-48
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Discovery and verification of urinary peptides in type 2 diabetes mellitus with kidney injury
2016Co-Authors: Fu Guangzhen, Chu Lina, Zhang ManAbstract:Varying degrees of renal injury could lead to different changes in urinary protein composition. We want to find urinary candidate peptide biomarkers in type 2 diabetic patients with different extents of kidney injury. Two sets of patients were recruited. Discovery set: weak cationic-exchange magnetic beads coupled with matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to profile the low-molecular weight peptidome in urine samples from type 2 diabetes patients with normoal-buminura and microalbuminuria. The differently expressed urinary peptides were screened by ClinProTools2.1 bioinformatics software and identified through nano-liquid chromatography-tandem mass spectrometry. Verification set: the above screened urinary peptides were validated by use matrix-assisted laser desorption ionization time-of-flight mass spectrometry on another group of type 2 diabetes patients with different extents use of kidney injury. In the screening and identification stages, seven urinary peptides were selected as the most promising biomarker candidates, and they were identified as fragments of vitronectin precursor, isoform 1 of Fibrinogen Alpha Chain precursor, prothrombin precursor and inter-Alpha-trypsin inhibitor heavy Chain H4. The diagnostic efficacy of these urinary peptides was evaluated by area under the receiver operating characteristic curve, and they were 0.767, 0.768, 0.868, 0.910, 0.860, 0.843, and 0.865, respectively. In the verification stage, m/z 1743.9, 2154, 2175.5, and 2184.9 were decreased as albumin-to-creatinine (Alb/Cre) increased and m/z 2231.1, 2430.8, and 2756.1 were elevated as Alb/Cre rose. These small molecule peptides are related to type 2 diabetes kidney damage, and they may play an important role in monitoring type 2 diabetes.National High Technology Research and Development Program of China [2014AA020901]; Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics [Z151100001615060]SCI(E)PubMedARTICLEmzhang99@aliyun.com111186-119424
Xiaohong Chang - One of the best experts on this subject based on the ideXlab platform.
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Fibrinogen Alpha Chain promotes the migration and invasion of human endometrial stromal cells in endometriosis through focal adhesion kinase protein kinase b matrix metallopeptidase 2 pathway
2020Co-Authors: Hongyan Cheng, Honglan Zhu, Xiaohong ChangAbstract:Fibrinogen Alpha Chain (FGA), a cell adhesion molecule, contains two arginyl-glycyl-aspartic acid (RGD) cell adhesion sequences. Our previous study demonstrated that FGA, as an up-regulated protein in endometriosis (EM), was closely related to disease severity and involved in the development of EM. However, the biological functions and underlying mechanism of FGA in EM have not been fully understood. To explore the roles of FGA in EM, we analyzed the effects of FGA on the biological behaviors of human primary eutopic endometrial stromal cells (EuESC). The results indicated FGA knockdown suppressed the migration and invasion ability of EuESC, which also altered the distribution of cytoskeletal filamentous and cell morphology. Western blot analysis demonstrated that knockdown of FGA attenuated the migration-related protein levels of vimentin and matrix metallopeptidase 2 (MMP-2), but not integrin subunit Alpha V (ITGAV) and integrin subunit beta 3 (ITGB3). Meanwhile, integrin-linked transduction pathways were detected. We found FGA knockdown significantly suppressed the expression of focal adhesion kinase (FAK) level and protein kinase B (AKT) phosphorylation, without extracellular-signal-regulated kinase (ERK) dependent pathways. Treatment with the AKT inhibitor MK2206 or RGD antagonist highly decreased the effects of FGA on the migration and invasion of EuESC. RGD antagonist treatment strongly inhibited FAK- and AKT-dependent pathways, but not ERK pathways. Our data indicated that FGA may enhance the migration and invasion of EuESC through RGD sequences binding integrin and activating the FAK/AKT/MMP-2 signaling pathway. This novel finding suggests that FGA may provide a novel potential approach to the treatment of EM, which provides a new way to understand the pathogenesis of EM.
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Fibrinogen Alpha Chain fga promotes the migration and invasion of human endometrial stromal cells in endometriosis through fak akt mmp 2 pathway
2020Co-Authors: Hui Li, Hongyan Cheng, Xue Ye, Xiaohong ChangAbstract:Fibrinogen Alpha Chain (FGA), a cell adhesion molecule, contains two arginyl-glycyl-aspartic acid (RGD) cell adhesion sequences. Our previous study demonstrated that FGA, as an up-regulated protein in endometriosis (EM), was closely related to disease severity and involved in the development of EM. However, the biological functional and underlying mechanism of FGA in EM have not been fully understood. To explore the roles of FGA in EM, we analyzed the effects of FGA on the biological behaviors of human primary eutopic endometrial stromal cells (EuESC). The results indicated FGA knockdown suppressed the migration and invasion ability of EuESC, which also altered the distribution of cytoskeletal filamentous and cell morphology. Western blot analysis demonstrated that knockdown of FGA attenuated the migration-related protein levels of vimentin and MMP-2, but not integrin subunit Alpha V (ITGAV), integrin subunit beta 3 (ITGB3). Meanwhile, integrin-linked transduction pathways were detected. We found FGA knockdown significantly suppressed the expression of FAK level and AKT phosphorylation, without ERK dependent pathways. Treatment with the AKT inhibitor MK2206 or RGD antagonist highly decreased the effects of FGA on the migration and invasion of EuESC. RGD antagonist treatment strongly inhibited FAK and AKT dependent pathways, but not ERK pathways. Our data indicated that FGA may enhance the migration and invasion of EuESC through RGD sequences binding integrin and activating the FAK/AKT/MMP-2 signaling pathway. This novel finding suggests that FGA may provide a novel potential approach to the treatment of EM, which provides a new way to understand the pathogenesis of endometriosis.
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Fibrinogen Alpha Chain is up regulated and affects the pathogenesis of endometriosis
2019Co-Authors: Ying Chen, Hongyan Cheng, Ma Ruiqiong, Heng Cui, Zhu Honglan, Xiaohong ChangAbstract:Research Question Fibrinogen Alpha Chain (FGA) was identified an upregulated differential protein and highly expressed in endometriosis patients in our previous study. This study investigated the expression and effects of FGA in endometriosis (EM). It also evaluated the effects of FGA on human endometrial stromal cells and studied its possible mechanism. Design Cross-sectional analysis of FGA expression in plasma and in eutopic and ectopic endometria from women with and without EM, is needed to further study the effects of FGA in human endometrial stromal cells to verify the role of FGA in EM women undergoing laparoscopic surgery for EM. Forty-four patients with EM and 32 healthy control subjects who donated plasma for FGA analysis, including 26 matched cases of eutopic and ectopic endometria from EM patients and 22 endometria from healthy control subjects were analyzed. Results The expression of FGA in serum and eutopic and ectopic endometrial tissue was significantly upregulated in endometriotic patients, while that in the eutopic endometrial tissues of the same patients did not significantly differ from that in ectopic endometrial tissue. High FGA levels in serum were correlated with disease stage and ovarian involvement, not affected by age and menstrual cycle. The knockdown of FGA expression by FGA siRNA inhibited hEM15A cellular adhesion, migration and invasion and attenuated the expression of MMP-2. Conclusions High expression of FGA in EM was closely related to disease severity and affected cell adhesion, migration, and invasion, which might play an important role in the pathogenesis of EM.
Marguerite Neermanarbez - One of the best experts on this subject based on the ideXlab platform.
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Fibrinogen geneva ii a new congenitally abnormal Fibrinogen Alpha Chain gly17asp with a review of similar mutations resulting in abnormal knob a
2014Co-Authors: Alessandro Casini, Marguerite Neermanarbez, Emmanuel De Maistre, Virginie Casinistuppi, Pierre Fontana, Philippe De MoerlooseAbstract:Congenital dysFibrinogenemias are characterized by biosynthesis of a structurally abnormal Fibrinogen molecule that exhibits reduced functional levels compared with the level of Fibrinogen antigen. To date a large number of mutations have been identified in patients with dysFibrinogenemia. Mutations occurring at the thrombin cleavage site (Arg16-Gly17 in the mature Alpha-Chain) at the amino-terminal end of the Fibrinogen Alpha Chain are a common cause of the disease. These mutations causing abnormal fibrin polymerization are associated with different phenotypes. Here, we report the identification of a novel heterozygous missense mutation of Glycine 17 (Gly17Asp) in a female patient with mild bleeding manifestations, and compare it with other previously reported mutations also resulting in abnormal knob A.
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Fibrinogen gene mutations accounting for congenital aFibrinogenemia
2006Co-Authors: Marguerite NeermanarbezAbstract:This article reviews recent progress made in understanding the molecular basis of congenital aFibrinogenemia, an autosomal recessive coagulation disorder characterized by the complete absence of detectable Fibrinogen. We have identified the first causative mutations for this disorder in a non-consanguineous Swiss family; these were homozygous deletions of approximately 11 kb of the Fibrinogen Alpha Chain (FGA) gene. Haplotype data implied that the deletions occurred on distinct ancestral chromosomes, suggesting that this region may be susceptible to deletion by a common mechanism. All the deletions were identical to the base pair, and probably resulted from non-homologous (illegitimate) recombination. In a subsequent study of 13 unrelated patients with congenital aFibrinogenemia we analyzed the FGA gene in order to identify the causative mutations, and to determine the prevalence of the 11-kb FGA deletion. Although this deletion was found in an additional unrelated patient, the most common mutation was at the donor splice site of FGA intron 4 (IVS4 + 1 G > T). Three frameshift mutations, two nonsense mutations, and one other splice site mutation were also characterized. Other studies identified one further FGA nonsense mutation, two FGB missense mutations, and one FGG nonsense mutation, all in homozygosity in a single patient. In conclusion, the majority of patients have truncating mutations in the FGA gene although, intuitively, all three Fibrinogen genes could be predicted to be equally implicated. These results will facilitate molecular diagnosis of the disorder, permit prenatal diagnosis for families who so desire, and pave the way for new therapeutic approaches such as gene therapy.
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congenital aFibrinogenemia identification and expression of a missense mutation in fgb impairing Fibrinogen secretion
2003Co-Authors: Paula H B Boltonmaggs, Michael A Morris, Philippe De Moerloose, Jeremy R Parr, Marguerite NeermanarbezAbstract:Congenital aFibrinogenemia is a rare autosomal recessive disorder characterized by complete absence of detectable Fibrinogen. We previously identified the first causative mutations for this disease: a homozygous deletion of approximately 11 kb of the Fibrinogen Alpha-Chain gene (FGA). Subsequent studies revealed that the great majority of aFibrinogenemia mutations are localized in FGA, but mutations were also found in FGG and FGB. Apart from 3 missense mutations identified in the C-terminal portion of FGB, all Fibrinogen gene mutations responsible for aFibrinogenemia are null. In this study, a young boy with aFibrinogenemia was found to be a compound heterozygote for 2 mutations in FGB: an N-terminal nonsense mutation W47X (exon 2) and a missense mutation (G444S, exon 8). Coexpression of the FGB G444S mutant cDNA in combination with wild-type FGA and FGG cDNAs demonstrated that Fibrinogen molecules containing the mutant beta Chain are able to assemble but are not secreted into the media, confirming the pathogenic nature of the identified mutation.
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prenatal diagnosis for congenital aFibrinogenemia caused by a novel nonsense mutation in the fgb gene in a palestinian family
2003Co-Authors: Marguerite Neermanarbez, Bassam Abulibdeh, Isabelle Bouchardy, Michael A MorrisAbstract:Congenital aFibrinogenemia is a rare autosomal recessive disorder characterized by the complete absence of detectable Fibrinogen. We previously identified the first causative mutations for this disease, homozygous deletions of approximately 11 kb of the Fibrinogen Alpha Chain gene (FGA). Subsequent analyses revealed that most aFibrinogenemia alleles are truncating mutations of FGA, although mutations in all 3 Fibrinogen genes, FGG, FGA and FGB have been identified. In this study, we performed the first prenatal diagnosis for aFibrinogenemia. The causative mutation in a Palestinian family was a novel nonsense mutation in the FGB gene, Trp467Stop (W467X). Expression of the Trp467Stop mutant FGB cDNA in combination with wild-type FGA and FGG cDNAs showed that Fibrinogen molecules containing the mutant beta Chain are not secreted into the media. The fetus was found to be heterozygous for the Trp467Stop mutation by direct sequencing and by linkage analysis, a result that was confirmed in the newborn by intermediate Fibrinogen levels.
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molecular analysis of the Fibrinogen gene cluster in 16 patients with congenital aFibrinogenemia novel truncating mutations in the fga and fgg genes
2001Co-Authors: Marguerite Neermanarbez, Ariane Honsberger, G Parlier, B Arnuti, Christine A Biron, Jeanneyvonne Borg, E Meili, Philippe De Moerloose, Sabine Eber, K PetersalonenAbstract:Congenital aFibrinogenemia is an autosomal recessive disorder characterized by the complete absence of detectable Fibrinogen. We previously identified the first causative mutations for this disease in a non-consanguineous Swiss family. These were homozygous deletions of approximately 11 kb of the Fibrinogen Alpha Chain gene (FGA). Our subsequent study revealed that the majority of cases were attributable to truncating mutations in FGA, with the most common mutation affecting the donor splice site in FGA intron 4 (IVS4+1 G-->T). Here, we report 13 further unrelated patients with mutations in FGA, confirming the relative importance of this gene compared with FGG and FGB in the molecular aetiology of aFibrinogenemia. Three other patients were homozygous for mutations in FGG. Eight novel mutations were identified: five in FGA and three in FGG. Sufficient mutation data is now available to permit an effective strategy for the genetic diagnosis of congenital aFibrinogenemia.
Fu Guangzhen - One of the best experts on this subject based on the ideXlab platform.
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Association of serum lipid metabolism with markers of urinary peptides in type 2 diabetes patients
2016Co-Authors: Li Jia, Fu Guangzhen, Wang Junjun, Zhang ManAbstract:Objective: To unveil the differently expressed urinary peptides that are associated with different stages of lipid control for type 2 diabetes mellitus. Methods: Patients with diagnosed type 2 diabetes mellitus (n=58) and normal controls (n=29) were included. Serum and urine samples were collected from these subjects. The fasting plasma glucose (FPG), hemoglobin A1c% (HbA1c), cholesterol (CHOL), triglyceride (TRIG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) were measured by ADVIA2400 Chemistry System. These type 2 diabetic patients were divided into two groups according to CHOL, TRIG, HDL and LDL, respectively. Urinary peptides were condensed by magnetic beads based weak cation exchange chromatography and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ClinProt was used to profile and screen the polypeptide patterns based on different methods of grouping in diabetic patients and normal controls. Nano-liquid chromatography-tandem mass spectrometry was used to identify these urinary peptides. Results: Serum CHOL negatively correlated with urinary peptide m/z 2756.5 (r=-0.315, P=0.016). Serum LDL negatively correlated with urinary peptide m/z 2756.5 (r=-0.390, P=0.002). Areas under the receiver operating characteristic of the three peptides (m/z 2756.5, m/z 3223.2 and m/z 4753.8) were 0.731, 0.673 and 0.602, respectively. The above-mentioned peptide m/z 2756.5 was further identified as fragment of Fibrinogen Alpha Chain precursor and m/z 3223.2 was fragment of prothrombin precursor. Conclusion: There were three urinary peptides (m/z 2756.5, m/z 3223.2 and m/z 4753.8) that differently expressed in different stages of serum lipid control in type 2 diabetes mellitus.National High Technology Research and Development Program of China [2014AA020901]; Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics [Z151100001615060]SCI(E)ARTICLEmzhang99@aliyun.com137-48
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Discovery and verification of urinary peptides in type 2 diabetes mellitus with kidney injury
2016Co-Authors: Fu Guangzhen, Chu Lina, Zhang ManAbstract:Varying degrees of renal injury could lead to different changes in urinary protein composition. We want to find urinary candidate peptide biomarkers in type 2 diabetic patients with different extents of kidney injury. Two sets of patients were recruited. Discovery set: weak cationic-exchange magnetic beads coupled with matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to profile the low-molecular weight peptidome in urine samples from type 2 diabetes patients with normoal-buminura and microalbuminuria. The differently expressed urinary peptides were screened by ClinProTools2.1 bioinformatics software and identified through nano-liquid chromatography-tandem mass spectrometry. Verification set: the above screened urinary peptides were validated by use matrix-assisted laser desorption ionization time-of-flight mass spectrometry on another group of type 2 diabetes patients with different extents use of kidney injury. In the screening and identification stages, seven urinary peptides were selected as the most promising biomarker candidates, and they were identified as fragments of vitronectin precursor, isoform 1 of Fibrinogen Alpha Chain precursor, prothrombin precursor and inter-Alpha-trypsin inhibitor heavy Chain H4. The diagnostic efficacy of these urinary peptides was evaluated by area under the receiver operating characteristic curve, and they were 0.767, 0.768, 0.868, 0.910, 0.860, 0.843, and 0.865, respectively. In the verification stage, m/z 1743.9, 2154, 2175.5, and 2184.9 were decreased as albumin-to-creatinine (Alb/Cre) increased and m/z 2231.1, 2430.8, and 2756.1 were elevated as Alb/Cre rose. These small molecule peptides are related to type 2 diabetes kidney damage, and they may play an important role in monitoring type 2 diabetes.National High Technology Research and Development Program of China [2014AA020901]; Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics [Z151100001615060]SCI(E)PubMedARTICLEmzhang99@aliyun.com111186-119424
Man Zhang - One of the best experts on this subject based on the ideXlab platform.
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Research Article The Difference Quantity of Urinary Peptides between Two Groups of Type 2 Diabetic Patients with or without Coronary Artery Disease
2016Co-Authors: Lina Chu, Man ZhangAbstract:which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. We aim to explore urinary biomarkers that could monitor CAD in type 2 diabetic patients. Materials and Methods. Urine samples from two groups, twenty-eight type 2 diabetic patients with coexisting CAD and thirty type 2 diabetic patients without CAD, were purified byMB-WCX and then analyzed byMALDI-TOF-MS. Subsequently, we compared the urinary peptide signatures of the two groups by use of ClinProTools2.1 and evaluated the potential ability of the differently expressed peptides to distinguish type 2 diabetic patients with coexisting CAD from type 2 diabetic patients without CAD by ROC analysis. Finally, the differently expressed peptides were identified by nanoliquid chromatography-tandem mass spectrometry. Results. There were six differently expressed peptides (m/z 1305.2, 1743.9, 2184.9, 2756.1, 3223.2, and 6196.1) between the two groups of subjects, and they were identified as fragments of isoform 1 of Fibrinogen Alpha Chain precursor, prothrombin precursor, and interAlpha-trypsin inhibitor heavy Chain H4. The diagnostic efficacy of m/z 2756.1 and m/z 3223.2 was better than the other peptides. Area under ROC of the m/z 2756.1, and m/z 3223.2 was 0.98 and 0.93, respectively. Conclusions. These urinary peptides are potential urinary biomarkers for monitoring of type 2 diabetic patients with CAD. 1
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Discovery of potential bladder cancer biomarkers by comparative urine proteomics and analysis.
2012Co-Authors: Ting Lei, Xuhong Zhao, Sheng Jin, Qian Meng, Hui Zhou, Man ZhangAbstract:Abstract Objective We searched for bladder tumor markers by analyzing urine samples from patients with bladder cancer and from normal controls. Methods Proteins in urine samples of patients with bladder cancer and with normal controls were systematically examined by 2-dimensional electrophoresis combined with matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The expression of the protein apolipoprotein A-I (apoA-I) was confirmed by Western blot analysis and further evaluated. Results We successfully obtained the 2-dimensional electrophoresis gel maps of urinary proteins in patients with bladder cancer and in normal controls. Thirty differentially expressed protein spots were successfully matched by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Combined with the SWISS-PROT database, only 14 proteins (beta-2-microglobulin, fatty acid–binding protein adipocyte, gelsolin, isoform 1 of gelsolin, myoglobin, isoform 2 of Fibrinogen Alpha Chain, apoA-I, prostaglandin D 2 synthase 21 kDa [brain], protein AMBP, transthyretin, keratin type II cytoskeletal 1, type II cytoskeletal 8, putative uncharacterized protein ALB, putative uncharacterized protein MASP2 [fragment]) were identified, including 2 putative proteins. Furthermore, apoA-I was confirmed by Western blot analysis, and the high level of apoA-I was found in urine samples from patients with bladder tumors compared with normal controls. Conclusions Analysis of urinary proteome may be a feasible, noninvasive, and efficient strategy for searching for potential bladder tumor biomarkers. A significant relationship of expressed apoA-I was established between bladder cancer and normal controls. We concluded that 14 differential spots included the apoA-I and would be potential urinary biomarkers for the diagnosis and surveillance of bladder cancer.