Dataset Information

Proteome Profiling of Urinary Exosomes Identifies Alpha 1-Antitrypsin and H2B1K as Diagnostic and Prognostic Biomarkers for Urothelial Carcinoma.

ABSTRACT: MALDI-TOF spectrometry has not been used for urinary exosome analysis. We used it for determining UC biomarkers. From 2012 to 2015, we enrolled 129 consecutive patients with UC and 62 participants without UC. Exosomes from their urine were isolated, and analyzed through MALDI-TOF spectrometry. Immunohistochemical (IHC) analysis of another 122 UC and 26 non-UC tissues was conducted to verify the discovered biomarkers. Two peaks at m/z 5593 (fragmented peptide of alpha-1-antitrypsin; sensitivity, 50.4%; specificity, 96.9%) and m/z 5947 (fragmented peptide of histone H2B1K sensitivity, 62.0%; specificity, 92.3%) were identified as UC diagnosis exosome biomarkers. UC patients with detectable histone H2B1K showed 2.29- and 3.11-fold increased risks of recurrence and progression, respectively, compared with those with nondetectable histone H2B1K. Verification results of IHC staining revealed significantly higher expression of alpha 1-antitrypsin (p?=?0.038) and H2B1K (p?=?0.005) in UC tissues than in normal tissues. The expression of alpha 1-antitrypsin and H2B1K in UC tissues was significantly correlated with UC grades (p?

SUBMITTER: Lin SY

PROVIDER: S-EPMC5043375 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proteome Profiling of Urinary Exosomes Identifies Alpha 1-Antitrypsin and H2B1K as Diagnostic and Prognostic Biomarkers for Urothelial Carcinoma.

Lin Shih-Yi SY Chang Chao-Hsiang CH Wu His-Chin HC Lin Ching-Chan CC Chang Kai-Po KP Yang Chi-Rei CR Huang Chi-Ping CP Hsu Wu-Huei WH Chang Chiz-Tzung CT Chen Chao-Jung CJ

Scientific reports 20160930

MALDI-TOF spectrometry has not been used for urinary exosome analysis. We used it for determining UC biomarkers. From 2012 to 2015, we enrolled 129 consecutive patients with UC and 62 participants without UC. Exosomes from their urine were isolated, and analyzed through MALDI-TOF spectrometry. Immunohistochemical (IHC) analysis of another 122 UC and 26 non-UC tissues was conducted to verify the discovered biomarkers. Two peaks at m/z 5593 (fragmented peptide of alpha-1-antitrypsin; sensitivity, ...[more]

PMID: 27686150

Similar Datasets

Project description:Gastric cancer (GC) is one of the leading causes of malignancy‑associated mortality worldwide. However, the underlying molecular mechanisms of GC are unclear and the prognosis of GC is poor. Therefore, it is important and urgent to explore the underlying mechanisms and screen for novel diagnostic and prognostic biomarkers, as well as therapeutic targets. In the current study, scale‑free gene co‑expression networks were constructed using weighted gene co‑expression network analysis, the potential associations between gene sets and clinical features were investigated, and the hub genes were identified. The gene expression profiles of GSE38749 were downloaded from the Gene Expression Omnibus database. RNA‑seq and clinical data for GC from The Cancer Genome Atlas were utilized for verification. Furthermore, the expression of candidate biomarkers in gastric tissues was investigated. Survival analysis was performed using Kaplan‑Meier and log‑rank test. The predictive role of candidate biomarkers in GC was evaluated using a receiver operator characteristic (ROC) curve. Gene Ontology, gene set enrichment analysis and gene set variation analysis methods were used to interpret the function of candidate biomarkers in GC. A total of 29 modules were identified via the average linkage hierarchical clustering. A significant module consisting of 48 genes associated with clinical traits was found; three genes with high connectivity in the clinical significant module were identified as hub genes. Among them, SLC5A6 and microfibril‑associated protein 2 (MFAP2) were negatively associated with the overall survival, and their expression was elevated in GC compared with non‑tumor tissues. Additionally, ROC curves indicated that SLC5A6 and MFAP2 showed a good diagnostic power in discriminating cancerous from normal tissues. SLC5A6 and MFAP2 were identified as novel diagnostic and prognostic biomarkers in GC patients; both of these genes were first reported here in connection with GC and deserved further research.

Project description:Many long noncoding RNAs (lncRNAs) are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC), several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1) was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106). Additionally, publicly available TCGA data was investigated for differential expression in UC tissues (set 2: N n = 19; T n = 252,) and correlation to overall survival (OS). All proposed candidates tended to be upregulated in tumour tissues, with the exception of MALAT1, which was rather diminished in cancer tissues of both data sets. However, strong overexpression was generally limited to individual tumour tissues and statistically significant overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue set 2, but for no candidate in set 1. Altered expression of individual lncRNAs was associated with overall survival, but not consistently between both patient cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with muscle-invasive tumours was significantly correlated with worse OS in both cohorts. Further analysis revealed that tumours with low TUG1 expression are characterized by a basal-squamous-like subtype signature accounting for the association with poor outcome. In conclusion, our study demonstrates that overexpression of the candidate lncRNAs is found in many UC cases, but does not occur consistently and strongly enough to provide reliable diagnostic or prognostic value as an individual biomarker. Subtype-dependent expression patterns of lncRNAs like TUG1 could become useful to stratify patients by molecular subtype, thus aiding personalized treatments.

Project description:Malignant mesothelioma is an aggressive asbestos-induced cancer, and affected patients have a median survival of approximately one year after diagnosis. It is often difficult to reach a conclusive diagnosis, and ancillary measurements of soluble biomarkers could increase diagnostic accuracy. Unfortunately, few soluble mesothelioma biomarkers are suitable for clinical application. Here we screened the effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass-spectrometry-based proteomics using isobaric tags for quantification and used narrow-range immobilized pH gradient/high-resolution isoelectric focusing (pH 4-4.25) prior to analysis by means of nano liquid chromatography coupled to MS/MS. More than 1,300 proteins were identified in pleural effusions from patients with malignant mesothelioma (n = 6), lung adenocarcinoma (n = 6), or benign mesotheliosis (n = 7). Data are available via ProteomeXchange with identifier PXD000531. The identified proteins included a set of known mesothelioma markers and proteins that regulate hallmarks of cancer such as invasion, angiogenesis, and immune evasion, plus several new candidate proteins. Seven candidates (aldo-keto reductase 1B10, apolipoprotein C-I, galectin 1, myosin-VIIb, superoxide dismutase 2, tenascin C, and thrombospondin 1) were validated by enzyme-linked immunosorbent assays in a larger group of patients with mesothelioma (n = 37) or metastatic carcinomas (n = 25) and in effusions from patients with benign, reactive conditions (n = 16). Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma. Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma. This analysis of the effusion proteome furthers our understanding of malignant mesothelioma, identified galectin 1 as a potential diagnostic biomarker, and highlighted several possible prognostic biomarkers of this disease.

Project description:Developing tumors continuously release nano-sized vesicles that represent circulating "fingerprints" of the tumor's identity. In gastrointestinal stromal tumor (GIST), we have previously reported that these tumors release "oncosomes" carrying the constitutively activated tyrosine kinase (TK) receptor KIT. Despite the clinical utility of TK inhibitors, such as imatinib mesylate (IM), recurrence and metastasis are clinical problems that urge the need to identify new tumor-derived molecules. To this aim, we performed the first high quality proteomic study of GIST-derived exosomes (GDEs) and identified 1,060 proteins composing the core GDE proteome (cGDEp). The cGDEp was enriched in diagnostic markers (e.g. KIT, CD34, ANO1, PROM1, PRKCQ, and ENG), as well as proteins encoded by genes previously reported expressed in GIST (e.g. DPP4, FHL1, CDH11, and KCTD12). Many of these proteins were validated using cell lines, patient-derived KIT+ exosomes, and GIST tissues. We further show that in vitro and in vivo-derived GDE, carry proteins associated with IM response, such as Sprouty homolog 4 (SPRY4), surfeit 4 (SURF4), ALIX, and the cGMP-dependent 3',5'-cyclic phosphodiesterase 2A (PDE2A). Additionally, we report that the total exosome levels and exosome-associated KIT and SPRY4 protein levels have therapeutic values. In fact, molecular characterization of in vivo-derived KIT+ exosomes indicate significant sorting of p-KITTyr719, total KIT, and SPRY4 after IM-treatment of metastatic patients as compared with the pre-IM levels. Our data suggest that analysis of circulating exosomes levels and molecular markers of IM response in GIST patients with primary and metastatic disease is suitable to develop liquid based biopsies for the diagnosis, prognosis, and monitoring of response to treatment of these tumors. In summary, these findings provide the first insight into the proteome of GIST-derived oncosomes and offers a unique opportunity to further understand their oncogenic elements which contribute to tumorigenesis and drug resistance. Data are available via ProteomeXchange with identifier PXD007997.

Dataset Information

Proteome Profiling of Urinary Exosomes Identifies Alpha 1-Antitrypsin and H2B1K as Diagnostic and Prognostic Biomarkers for Urothelial Carcinoma.

Publications

Proteome Profiling of Urinary Exosomes Identifies Alpha 1-Antitrypsin and H2B1K as Diagnostic and Prognostic Biomarkers for Urothelial Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets