scholarly journals Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers

2018 ◽  
Author(s):  
Tiannan Guo ◽  
Li Li ◽  
Qing Zhong ◽  
Niels J Rupp ◽  
Konstantina Charmpi ◽  
...  
Keyword(s):  
Technological Progress ◽  
Biomarker Discovery ◽  
Proteome Analysis ◽  
Tissue Microarrays ◽  
Protein Biomarker ◽  
Pressure Cycling ◽  
Pressure Cycling Technology ◽  
New Perspective ◽  
High Degree ◽  
Independent Cohort

AbstractMany tumors are characterized by large genomic heterogeneity and it remains unclear to what extent this impacts on protein biomarker discovery. Here, we quantified proteome intra-tissue heterogeneity (ITH) based on a multi-region analysis of 30 biopsy-scale prostate tissues using pressure cycling technology and SWATH mass spectrometry. We quantified 8,248 proteins and analyzed the ITH of 3,700 proteins. The level of ITH varied significantly depending on proteins and tissue types. Benign tissues exhibited generally more complex ITH patterns than malignant tissues. Spatial variability of ten prostate biomarkers was further validated by immunohistochemistry in an independent cohort (n=83) using tissue microarrays. PSA was preferentially variable in benign prostatic hyperplasia, while GDF15 substantially varied in prostate adenocarcinomas. Further, we found that DNA repair pathways exhibited a high degree of variability in tumorous tissues, which may contribute to the genetic heterogeneity of tumors. This study conceptually adds a new perspective to protein biomarker discovery by quantifying spatial proteome variation and it demonstrates the feasibility by exploiting recent technological progress.

scholarly journals Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers

2018 ◽  
Vol 1 (2) ◽  
pp. e201800042 ◽  
Author(s):  
Tiannan Guo ◽  
Li Li ◽  
Qing Zhong ◽  
Niels J Rupp ◽  
Konstantina Charmpi ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Specific Antigen ◽  
Proteome Analysis ◽  
Tissue Microarrays ◽  
Protein Biomarker ◽  
Pressure Cycling ◽  
Pressure Cycling Technology ◽  
New Perspective ◽  
High Degree ◽  
Independent Cohort

It remains unclear to what extent tumor heterogeneity impacts on protein biomarker discovery. Here, we quantified proteome intra-tissue heterogeneity (ITH) based on a multi-region analysis of prostate tissues using pressure cycling technology and Sequential Windowed Acquisition of all THeoretical fragment ion mass spectrometry. We quantified 6,873 proteins and analyzed the ITH of 3,700 proteins. The level of ITH varied depending on proteins and tissue types. Benign tissues exhibited more complex ITH patterns than malignant tissues. Spatial variability of 10 prostate biomarkers was validated by immunohistochemistry in an independent cohort (n = 83) using tissue microarrays. Prostate-specific antigen was preferentially variable in benign prostatic hyperplasia, whereas growth/differentiation factor 15 substantially varied in prostate adenocarcinomas. Furthermore, we found that DNA repair pathways exhibited a high degree of variability in tumorous tissues, which may contribute to the genetic heterogeneity of tumors. This study conceptually adds a new perspective to protein biomarker discovery: it suggests that recent technological progress should be exploited to quantify and account for spatial proteome variation to complement biomarker identification and utilization.

Proteome Analysis of Isolated Perfused Organ Effluent as a Novel Model for Protein Biomarker Discovery

2006 ◽  
Vol 5 (1) ◽  
pp. 177-182 ◽  
Author(s):  
John M. Koomen ◽  
Christopher R. Wilson ◽  
Patrick Guthrie ◽  
Matthew J. Androlewicz ◽  
Ryuji Kobayashi ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Proteome Analysis ◽  
Protein Biomarker ◽  
Novel Model

scholarly journals Upgrading the Repertoire of miRNAs in Gastric Adenocarcinoma to Provide a New Resource for Biomarker Discovery

2019 ◽  
Vol 20 (22) ◽  
pp. 5697 ◽  
Author(s):  
Michelle E. Pewarchuk ◽  
Mateus C. Barros-Filho ◽  
Brenda C. Minatel ◽  
David E. Cohn ◽  
Florian Guisier ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
Biomarker Discovery ◽  
The Cancer Genome Atlas ◽  
Small Rna Sequencing ◽  
Sequencing Data ◽  
Specific Expression ◽  
Novel Mirna ◽  
Cancer Genome Atlas ◽  
Context Specific ◽  
Independent Cohort

Recent studies have uncovered microRNAs (miRNAs) that have been overlooked in early genomic explorations, which show remarkable tissue- and context-specific expression. Here, we aim to identify and characterize previously unannotated miRNAs expressed in gastric adenocarcinoma (GA). Raw small RNA-sequencing data were analyzed using the miRMaster platform to predict and quantify previously unannotated miRNAs. A discovery cohort of 475 gastric samples (434 GA and 41 adjacent nonmalignant samples), collected by The Cancer Genome Atlas (TCGA), were evaluated. Candidate miRNAs were similarly assessed in an independent cohort of 25 gastric samples. We discovered 170 previously unannotated miRNA candidates expressed in gastric tissues. The expression of these novel miRNAs was highly specific to the gastric samples, 143 of which were significantly deregulated between tumor and nonmalignant contexts (p-adjusted < 0.05; fold change > 1.5). Multivariate survival analyses showed that the combined expression of one previously annotated miRNA and two novel miRNA candidates was significantly predictive of patient outcome. Further, the expression of these three miRNAs was able to stratify patients into three distinct prognostic groups (p = 0.00003). These novel miRNAs were also present in the independent cohort (43 sequences detected in both cohorts). Our findings uncover novel miRNA transcripts in gastric tissues that may have implications in the biology and management of gastric adenocarcinoma.

scholarly journals The combined detection of Amphiregulin, Cyclin A1 and DDX20/Gemin3 expression predicts aggressive forms of oral squamous cell carcinoma

2021 ◽  
Author(s):  
Ekaterina Bourova-Flin ◽  
Samira Derakhshan ◽  
Afsaneh Goudarzi ◽  
Tao Wang ◽  
Anne-Laure Vitte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell ◽  
Large Scale ◽  
Biomarker Discovery ◽  
Gene Expression Signature ◽  
Predictive Biomarkers ◽  
Specific Gene ◽  
Specific Expression ◽  
Intrinsic Nature ◽  
Independent Cohort

Abstract Background Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programmes. A specifically designed strategy was applied to oral squamous cell carcinomas (OSCC) in order to detect ectopic gene activations and develop a prognostic stratification test. Methods A dedicated original prognosis biomarker discovery approach was implemented using genome-wide transcriptomic data of OSCC, including training and validation cohorts. Abnormal expressions of silent genes were systematically detected, correlated with survival probabilities and evaluated as predictive biomarkers. The resulting stratification test was confirmed in an independent cohort using immunohistochemistry. Results A specific gene expression signature, including a combination of three genes, AREG, CCNA1 and DDX20, was found associated with high-risk OSCC in univariate and multivariate analyses. It was translated into an immunohistochemistry-based test, which successfully stratified patients of our own independent cohort. Discussion The exploration of the whole gene expression profile characterising aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Experimental targeting of CCNA1 in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting that CCNA1 could be a good target for therapeutic approaches.

scholarly journals A phasianid bird from the Pleistocene of Tainan: the very first avian fossil from Taiwan

2021 ◽  
Author(s):  
Cheng-Hsiu Tsai ◽  
Gerald Mayr
Keyword(s):  
Fossil Birds ◽  
Phasianus Colchicus ◽  
Diagnostic Features ◽  
Physical Evidence ◽  
Evolutionary Origins ◽  
Geological Past ◽  
Fossil Bird ◽  
New Perspective ◽  
High Degree ◽  
Unambiguous Assignment

AbstractTaiwan accommodates more than 600 avian species, including about 30 endemic ones. As yet, however, no fossil birds have been scientifically documented from Taiwan, so that the evolutionary origins of this diversified avifauna remain elusive. Here we report on the very first fossil bird from Taiwan. This Pleistocene specimen, a distal end of the left tarsometatarsus, shows diagnostic features of the galliform Phasianidae, including an asymmetric plantar articular facet trochlea metatarsi III. Our discovery of a Pleistocene phasianid from Taiwan opens a new perspective on studies of the evolution of the avifauna in Taiwan because the fossil shows that careful search for fossils in suitable localities has the potential of recovering avian remains. In general, East Asia has an extremely poor avian fossil record, especially if terrestrial birds are concerned, which impedes well-founded evolutionary scenarios concerning the arrival of certain groups in the area. The Phasianidae exhibit a high degree of endemism in Taiwan, and the new fossil presents the first physical evidence for the presence of phasianids on the island, some 400,000–800,000 years ago. The specimen belongs to a species the size of the three larger phasianids occurring in Taiwan today (Syrmaticus mikado, Lophura swinhoii, and Phasianus colchicus). Still, an unambiguous assignment to either of these species is not possible due to the incomplete nature of the left tarsometatarsus. Because the former two species are endemic to Taiwan, the fossil has the potential to yield the first data on their existence in the geological past of Taiwan if future finds allow identification on species-level.

scholarly journals Cerebrospinal fluid extracellular vesicle enrichment for protein biomarker discovery in neurological disease; multiple sclerosis

2017 ◽  
Vol 6 (1) ◽  
pp. 1369805 ◽  
Author(s):  
Joanne L. Welton ◽  
Samantha Loveless ◽  
Timothy Stone ◽  
Chris von Ruhland ◽  
Neil P. Robertson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Disease ◽  
Biomarker Discovery ◽  
Extracellular Vesicle ◽  
Protein Biomarker

scholarly journals Transcriptome and Proteome Research in Veterinary Science: What Is Possible and What Questions Can Be Asked?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Robert Klopfleisch ◽  
Achim D. Gruber
Keyword(s):  
Sequential Analysis ◽  
Biomarker Discovery ◽  
Expression Patterns ◽  
Proteome Analysis ◽  
Shotgun Proteomics ◽  
Complete Analysis ◽  
Biological Research ◽  
Veterinary Research ◽  
Gene Sets ◽  
2D Gel

In recent years several technologies for the complete analysis of the transcriptome and proteome have reached a technological level which allows their routine application as scientific tools. The principle of these methods is the identification and quantification of up to ten thousands of RNA and proteins species in a tissue, in contrast to the sequential analysis of conventional methods such as PCR and Western blotting. Due to their technical progress transcriptome and proteome analyses are becoming increasingly relevant in all fields of biological research. They are mainly used for the explorative identification of disease associated complex gene expression patterns and thereby set the stage for hypothesis-driven studies. This review gives an overview on the methods currently available for transcriptome analysis, that is, microarrays, Ref-Seq, quantitative PCR arrays and discusses their potentials and limitations. Second, the most powerful current approaches to proteome analysis are introduced, that is, 2D-gel electrophoresis, shotgun proteomics, MudPIT and the diverse technological concepts are reviewed. Finally, experimental strategies for biomarker discovery, experimental settings for the identification of prognostic gene sets and explorative versus hypothesis driven approaches for the elucidation of diseases associated genes and molecular pathways are described and their potential for studies in veterinary research is highlighted.

scholarly journals Tutorial: best practices and considerations for mass-spectrometry-based protein biomarker discovery and validation

2021 ◽  
Author(s):  
Ernesto S. Nakayasu ◽  
Marina Gritsenko ◽  
Paul D. Piehowski ◽  
Yuqian Gao ◽  
Daniel J. Orton ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Best Practices ◽  
Biomarker Discovery ◽  
Protein Biomarker

scholarly journals Who Keeps the Gate? Digital Gatekeeping in New Media

2021 ◽  
Vol 64 (2 (246)) ◽  
pp. 91-99
Author(s):  
Karolina Pałka-Suchojad
Keyword(s):  
Social Media ◽  
New Media ◽  
Technological Progress ◽  
Media Ecosystem ◽  
The Media ◽  
Echo Chamber ◽  
New Perspective ◽  
Network Diffusion

This article is the result of noticing the need to transpose the gatekeeping theory. Technological progress has left its mark on the media ecosystem, generating and then strengthening the convergence processes, and has also changed the understanding of gatekeeping. The architecture of new media, especially social media, places gatekeeping in the context of the network. This allows one to look at the classically understood process from a new perspective, in which the key is to base the concept on network diffusion. Contemporary gatekeeping should be analyzed in the context of such mechanisms as: information bubble, echo chamber, filtering information by users and algorithms. Basic conceptual categories, the gate and the keeper, are also modified. There is a noticeable trend towards the transformation of gatekeeping towards gatewatching, in which social media users do not create their own gates, but observe and use already existing gates. Gatekeeping in the era of social media makes the audience an important element of it, moving towards secondary gatekeeping.

scholarly journals Rat mesangial cells and matrix metalloproteinase inhibitor: inhibition of 72-kD type IV collagenase (MMP-2) and of cell proliferation.

1997 ◽  
Vol 8 (3) ◽  
pp. 395-405 ◽  
Author(s):  
K Steinmann-Niggli ◽  
M Lukes ◽  
H P Marti
Keyword(s):  
Mesangial Cells ◽  
Inflammatory Diseases ◽  
Constitutive Expression ◽  
Matrix Metalloproteinase Inhibitor ◽  
Type Iv Collagenase ◽  
Type Iv ◽  
Synthetic Inhibitor ◽  
Inflammatory Phenotype ◽  
New Perspective ◽  
High Degree

The synthetic inhibitor of matrix metalloproteinases (MMP) Ro 31-9790, a hydroxamic-acid derivative, was investigated for its effect on rat mesangial cells (MC) in culture. For these studies, proliferating MC with a high degree of constitutive expression of a MMP, the 72-kD Type IV collagenase (gelatinase A, MMP-2), were chosen, because they reflect aspects of an inflammatory phenotype that may occur during certain forms of glomerular inflammatory diseases. Ro 31-9790 inhibited activity of the rat MC MMP-2 in a concentration-dependent and competitive fashion, as analyzed by quantitative densitometry and by a continuously recording fluorescent assay. Furthermore, Ro 31-9790 inhibited the proliferation rate of cultured rat MC in a concentration-dependent and at least partially reversible manner without affecting cell viability. It was concluded that the application of synthetic MMP inhibitors may offer a new perspective for the therapy of mesangial cell-derived forms of glomerulonephritis.

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