scholarly journals Secretome Proteomic Approaches for Biomarker Discovery: An Update on Colorectal Cancer

Medicina ◽  
2020 ◽  
Vol 56 (9) ◽  
pp. 443
Author(s):  
Armando Cevenini ◽  
Stefania Orrù ◽  
Esther Imperlini
Keyword(s):  
Colorectal Cancer ◽  
Biomarker Discovery ◽  
Dynamic Range ◽  
Biological Fluids ◽  
Label Free ◽  
Protein Markers ◽  
Comprehensive Overview ◽  
Bioinformatic Tools ◽  
Complete Translation

Searching for new cancer-related biomarkers is a key priority for the early detection of solid tumors, such as colorectal cancer (CRC), in clinically relevant biological fluids. The cell line and/or tumor tissue secretome represents a valuable resource for discovering novel protein markers secreted by cancer cells. The advantage of a secretome analysis is the reduction of the large dynamic range characterizing human plasma/serum, and the simultaneous enrichment of low abundance cancer-secreted proteins, thereby overcoming the technical limitations underlying the direct search in blood samples. In this review, we provided a comprehensive overview of recent studies on the CRC secretome for biomarker discovery, focusing both on methodological and technical aspects of secretome proteomic approaches and on biomarker-independent validation in CRC patient samples (blood and tissues). Secretome proteomics are mainly based on LC-MS/MS analyses for which secretome samples are either in-gel or in-solution trypsin-digested. Adequate numbers of biological and technical replicates are required to ensure high reproducibility and robustness of the secretome studies. Moreover, another major challenge is the accuracy of proteomic quantitative analysis performed by label-free or labeling methods. The analysis of differentially expressed proteins in the CRC secretome by using bioinformatic tools allowed the identification of potential biomarkers for early CRC detection. In this scenario, this review may help to follow-up the recent secretome studies in order to select promising circulating biomarkers to be validated in larger screenings, thereby contributing toward a complete translation in clinical practice.

scholarly journals Proteomic analysis of extracellular vesicles in cerebrospinal fluid of patients with Alzheimer’s disease

2020 ◽  
Author(s):  
Davide Chiasserini ◽  
Irene Bijnsdorp ◽  
Giovanni Bellomo ◽  
Pier Luigi Orvietani ◽  
Sander R. Piersma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Extracellular Vesicles ◽  
Biomarker Discovery ◽  
Neurodegenerative Disorder ◽  
High Resolution Mass Spectrometry ◽  
Biological Fluids ◽  
Protein Profile ◽  
Protein Markers

AbstractCerebrospinal fluid (CSF) contains different types of extracellular vesicles (EVs) with undisclosed biomarker potential for neurodegenerative diseases. The aims of the present study were: i) to compare the proteome EVs isolated using different ultracentrifugation speed ii) to preliminary explore the EVs proteome in a common neurodegenerative disorder, Alzheimer’s disease (AD) compared to neurological controls. CSF samples from control subjects and AD patients were pooled separately (15 mL) and subjected to ultracentrifugation (UC) at different speeds (20,000g and 100,000g) to isolate separate EV fractions (P20 and P100). The proteome was analysed using high-resolution mass spectrometry (LC-MS/MS) and comparisons were made using bioinformatic analysis. EVs isolated at 100,000g (P100) had a proteome consistent with vesicles secreted via an ESCRT-dependent mechanism, being highly enriched in alix (PDCD6IP), syntenin-1 (SDCBP) and TSG101. EVs isolated at 20,000g were substantially different, showing enrichment in cytoskeletal and cell adhesion molecules. The pools from patients diagnosed with AD showed a distinct protein profile of CSF EVs, with increased levels of ADAM10, SPON1, CH3IL1 and MDK in the P100 fraction. CSF EV offer a new potential biosource of protein markers for AD detection and a complementary framework to the analysis of whole biological fluids for biomarker discovery.

scholarly journals Metabolomic profile of colorectal cancer patients and its clinical implications

2020 ◽  
Vol 25 (6) ◽  
pp. 2045-2054
Author(s):  
CLAUDIU RĂCHIERIU ◽  
◽  
FLORIN GRAUR ◽  
EMIL MOIS ◽  
CARMEN SOCACIU ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Diagnosis ◽  
Biological Fluids ◽  
Tumor Staging ◽  
Public Health Issue ◽  
Screening Methods ◽  
Tissue Samples ◽  
Medical Databases ◽  
Colorectal Cancer Patients

Background: Colorectal Cancer (CRC) is a great public health issue and the outcomes of treatment depends on early diagnosis. Metabolomics may provide biomarkers for early diagnosis, staging, prognosis and follow-up. Methods: The authors searched for the results of the published studies existing in medical databases (PubMed) for all the changes in the main metabolic pathways (carbohydrate, lipid, aminoacid, nucleotide and other important metabolites) of the CRC patients and how the metabolic changes can be used as biomarkers, for tumor staging, prognosis and follow-up. Results: While most of the metabolites values in biological fluids or tissue samples are modified (either increased or decreased) and the results are usually constant across the studies it seems that only patterns of metabolites (fingerprints of 5, 15 or even 30 metabolites) can be used for the regarding issues mentioned above. Conclusion: Some studies conclude that some metabolomic models are statistically much better than current existing markers and may become screening methods in the near future.

scholarly journals Current Status and Advances in Quantitative Proteomic Mass Spectrometry

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Valerie C. Wasinger ◽  
Ming Zeng ◽  
Yunki Yau
Keyword(s):  
Mass Spectrometry ◽  
Quantitative Proteomics ◽  
Biomarker Discovery ◽  
Current Status ◽  
Label Free ◽  
Stable Isotope Labelling ◽  
Complex Samples ◽  
Bioinformatic Tools ◽  
Critical Overview ◽  
Proteins And Peptides

The accurate quantitation of proteins and peptides in complex biological systems is one of the most challenging areas of proteomics. Mass spectrometry-based approaches have forged significant in-roads allowing accurate and sensitive quantitation and the ability to multiplex vastly complex samples through the application of robust bioinformatic tools. These relative and absolute quantitative measures using label-free, tags, or stable isotope labelling have their own strengths and limitations. The continuous development of these methods is vital for increasing reproducibility in the rapidly expanding application of quantitative proteomics in biomarker discovery and validation. This paper provides a critical overview of the primary mass spectrometry-based quantitative approaches and the current status of quantitative proteomics in biomedical research.

scholarly journals Label-Free Peptide-Based Biosensor for Express Detection of Protein Markers of Acute Cardiovascular Conditions in Biological Fluids

Proceedings ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 8
Author(s):  
Nikita Sitkov ◽  
Tatiana Zimina ◽  
Vladimir Karasev ◽  
Olesya Naretskaya ◽  
Margarita Kiseleva
Keyword(s):  
Uv Light ◽  
Detection System ◽  
Biological Fluids ◽  
Clinical Sample ◽  
Microfluidic Channel ◽  
Label Free ◽  
Protein Markers ◽  
Protein Fluorescence ◽  
Peptide Aptamers ◽  
Biosensor System

Acute cardiovascular conditions require prompt assistance, which depends on a timely and accurate diagnosis. This could be achieved by using biosensor systems based on peptide aptamers capable of selectively binding protein markers of diseases. In this work, a label-free biosensor system based on fluorometric registration of the formation of a “peptide aptamer—target protein” complex is considered. It comprises a microfluidic subsystem integrated with arrays of sites with immobilized peptide aptamers, coupled with an optical detection system. The clinical sample of the whole blood is loaded into the inlet basin, where the cells are separated and plasma flows into the microfluidic channel for analysis. Peptide aptamers were created using the molecular complement search technique based on the search for systems of conjugated ion-hydrogen bonds in the three-dimensional structures of target proteins. The technology for manufacturing a microfluidic chip is a combination of thick-film and photolithography technologies based on the SU-8 photoresist, for which the relief and surface morphology have been studied. The composition of the biochip layers is selected in such a way that ultraviolet light with a wavelength of 280 nm passes through an inlet window, excites fluorescence inside the channel, which passes through the glass window, which absorbs UV-light. This wavelength accounts for the maximum absorption of aromatic amino acids—tyrosine and tryptophan. In this case, one of the last layers is a luminophore layer for re-emission of protein fluorescence as a visible light. The reading platform includes a 280 nm LED, a video sensor, 3D-printed PLA tooling, and software for processing and analyzing the received signal.

Circulating matrix metaloproteinases as biomarkers in colorectalcancer

2020 ◽  
Vol 99 (9) ◽  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Markers ◽  
Point Of View ◽  
Tissue Inhibitors ◽  
Natural Tissue

The aim of this research is to offer comprehensive point of view related to perspective tumor markers called matrix metaloproteinases and their natural tissue inhibitors. Those markers are potentially useable mainly in postoperative follow-up in patients with colorectal cancer.

scholarly journals Metabolic Evaluation of Urine from Patients Diagnosed with High Grade (HG) Bladder Cancer by SPME-LC-MS Method

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2194
Author(s):  
Kamil Łuczykowski ◽  
Natalia Warmuzińska ◽  
Sylwia Operacz ◽  
Iga Stryjak ◽  
Joanna Bogusiewicz ◽  
...  
Keyword(s):  
Thin Film ◽  
Bladder Cancer ◽  
High Performance ◽  
Biomarker Discovery ◽  
Solid Phase ◽  
Biological Fluids ◽  
Reversed Phase ◽  
Control Group ◽  
Metabolic Evaluation ◽  
Metabolomic Profiling

Bladder cancer (BC) is a common malignancy of the urinary system and a leading cause of death worldwide. In this work, untargeted metabolomic profiling of biological fluids is presented as a non-invasive tool for bladder cancer biomarker discovery as a first step towards developing superior methods for detection, treatment, and prevention well as to further our current understanding of this disease. In this study, urine samples from 24 healthy volunteers and 24 BC patients were subjected to metabolomic profiling using high throughput solid-phase microextraction (SPME) in thin-film format and reversed-phase high-performance liquid chromatography coupled with a Q Exactive Focus Orbitrap mass spectrometer. The chemometric analysis enabled the selection of metabolites contributing to the observed separation of BC patients from the control group. Relevant differences were demonstrated for phenylalanine metabolism compounds, i.e., benzoic acid, hippuric acid, and 4-hydroxycinnamic acid. Furthermore, compounds involved in the metabolism of histidine, beta-alanine, and glycerophospholipids were also identified. Thin-film SPME can be efficiently used as an alternative approach to other traditional urine sample preparation methods, demonstrating the SPME technique as a simple and efficient tool for urinary metabolomics research. Moreover, this study’s results may support a better understanding of bladder cancer development and progression mechanisms.

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