Circulating Proteins as Diagnostic Markers in Gastric Cancer

Gastric cancer (GC) is a highly malignant disease affecting humans worldwide and has a poor prognosis. Most GC cases are detected at advanced stages due to the cancer lacking early detectable symptoms. Therefore, there is great interest in improving early diagnosis by implementing targeted prevention strategies. Markers are necessary for early detection and to guide clinicians to the best personalized treatment. The current semi-invasive endoscopic methods to detect GC are invasive, costly, and time-consuming. Recent advances in proteomics technologies have enabled the screening of many samples and the detection of novel biomarkers and disease-related signature signaling networks. These biomarkers include circulating proteins from different fluids (e.g., plasma, serum, urine, and saliva) and extracellular vesicles. We review relevant published studies on circulating protein biomarkers in GC and detail their application as potential biomarkers for GC diagnosis. Identifying highly sensitive and highly specific diagnostic markers for GC may improve patient survival rates and contribute to advancing precision/personalized medicine

Molecular Signature in HCV-Positive Lymphomas

Hepatitis C virus (HCV) is a positive, single-stranded RNA virus, which has been associated to different subtypes of B-cell non-Hodgkin lymphoma (B-NHL). Cumulative evidence suggests an HCV-related antigen driven process in the B-NHL development. The underlying molecular signature associated to HCV-related B-NHL has to date remained obscure. In this review, we discuss the recent developments in this field with a special mention to different sets of genes whose expression is associated with BCR coupled to Blys signaling which in turn was found to be linked to B-cell maturation stages and NF-κb transcription factor. Even if recent progress on HCV-B-NHL signature has been made, the precise relationship between HCV and lymphoma development and phenotype signature remain to be clarified

Levels of Soluble E-Cadherin in Breast, Gastric, and Colorectal Cancers

Soluble E-cadherin is a 80 kDa protein fragment coming from the proteolytic cleavage of the extracellular domain of the full length epithelial cadherin, a molecule involved in cell adhesion/polarity and tissue morphogenesis. In comparison with normal epithelia, cancer cells show a decreased cadherin-mediated intercellular adhesion, and sE-cad levels normally increase in body fluids (blood and urine). This review focuses on soluble E-cadherin in sera of patients affected by three solid cancers (breast, gastric, and colorectal cancers) and how its levels correlate or not with some cancer parameters (e.g., dimension, progression, and localisation). We will describe the main proteomics approaches adopted to measure sE-cad bothin vivoandin vitroand the most important findings about its behaviour in cancer dynamics.</jats:p

Levels of Soluble E-Cadherin in Breast, Gastric, and Colorectal Cancers

Soluble E-cadherin is a 80 kDa protein fragment coming from the proteolytic cleavage of the extracellular domain of the full length epithelial cadherin, a molecule involved in cell adhesion/polarity and tissue morphogenesis. In comparison with normal epithelia, cancer cells show a decreased cadherin-mediated intercellular adhesion, and sE-cad levels normally increase in body fluids (blood and urine). This review focuses on soluble E-cadherin in sera of patients affected by three solid cancers (breast, gastric, and colorectal cancers) and how its levels correlate or not with some cancer parameters (e.g., dimension, progression, and localisation). We will describe the main proteomics approaches adopted to measure sE-cad both in vivo and in vitro and the most important findings about its behaviour in cancer dynamics. The Soluble E-Cadherin The E-cadherins (E-cad), or &quot;classical&quot; cadherins of type I, belong to the large family of cadherins, transmembrane or membrane-associated glycoproteins, mediating cell-cell adhesion and playing a pivotal role in epithelial cell behaviour and tissue morphogenesis/remodelling (reviewed in Other mechanisms potentially influencing E-cad normal functions such as its binding to other proteins include the levels of its phosphorylation together with specific proteolytic events At present, serum levels of sE-cad are known to increase in patients affected by cancer (e.g., breast, gastric, and colorectal cancers; Table 1) in respect to healthy patients, so that there is a growing interest in sE-cad as &quot;candidate sentinel molecule&quot; in cancer research (reviewed by Generally, since the first observations in 1990, the global decrease in E-cad in dissociating/metastasising cancer cells was accompanied by an increase in sE-cad fragments in patient sera, so that the first emerging idea was to consider the soluble sE-cad as originating from the rapid turnover of tumor cells and to relate the sE-cad concentration to the tumor size. Here, we report proteomics applied to the characterization of sE-cad amount in three solid cancers (breast, gastric, and colorectal cancers) and describe the most common techniques adopted since sE-cad discovery. Since sE-cad presence is not only limited to these three pathologies, we also briefly summarized the findings of other works in a recapitulative table Proteomics Approaches Applied to Cadherin Characterization Western Blotting (WB). In most reports, in patients, the sE-cad amount is also evaluated with WB after protein separation by one-dimensional acrylamide gel electrophoresis (1-DE), and it can be compared with the full length E-cad expression, which in turn is analysed by immunostaining in situ. WB analyses reveal the presence of multiple bands, among which are the full length E-cad at 120 kDa and the sEcad at 80 kDa. Reverse Phase Protein Array (RPPA). Another targeted approach was used by Perez-Rivas et al. Soluble E-Cadherin in Breast Cancer In BC patients, first studies started in 2005 when Hofmann and colleagues measured sE-cad levels in sera of 133 patients before and after neoadjuvant chemotherapy with an enzymebased immunoassay technique, and they positively correlated them with the pre-and posttherapeutic tumor size as well as the disease-free interval [34] evaluated by 1-DE and WB (anti-HECD-1) the release of sE-cad in the media of MCF-7/AZ BC cells grown in presence or absence of the nerve growth factor (NGF), a small secreted protein that is important for the development and survival of certain target neurons, and their results supported a relation between sE-cad levels and the BC cell acquisition of an invasive phenotype. In order to identify markers for BC patient response to surgery, the following analyses were addressed to characterize the differential serum proteomes &quot;before versus after surgery&quot; by RPP

Identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemo-radiotherapy

Preoperative neoadjuvant chemoradiotherapy (nCRT) is the gold standard in locally advanced rectal cancer, only 10-30% of patients achieving benefits. Currently, there is a need of a reliable selection of markers for the identification of poor or non-responders prior to therapy. In this work, we compared protein profiles before therapy of patients differing in their responses to nCRT to find novel predictive markers of response to therapy. Patients were grouped into 3 groups according to their tumor regression grading (TRG) after surgery: 'TRG 1-2', good responders, 'TRG 3' and 'TRG 4', poor responders. Paired surgical specimens of rectal cancer and healthy (histologically confirmed) rectal tissues from 15 patients were analysed before nCRT by two dimensional difference in gel electrophoresis followed by mass spectrometry. Thirty spots were found as differentially expressed (p < 0.05). Among them, 3 spots (spots 471, 683 and 684) showed an increased amount of protein in poor responders compared with good responders, and they were more tumor associated compared with healthy tissues. Proteins of these spots were identified as fibrinogen beta chain fragment D, actin isoforms, B9 and B5 serpins, cathepsin D isoforms and peroxiredoxin-4. In an independent validation set of 20 rectal carcinomas we validated the increased fibrinogen beta chain abundance before nCRT in poor responders by immunoblotting. In conclusion, we propose a risk-stratification tool in predicting the response to nCRT treatment in rectal cancer based on the quantity of these proteins

Classical Hodgkin’s Lymphoma in the Era of Immune Checkpoint Inhibition

The ligation of programmed cell death 1 (PD-1) with programmed cell death ligand PD-L activates the immune checkpoint leading to T-cell dysfunction, exhaustion, and tolerance, especially in Hodgkin lymphoma (HL) where the PD-L/ Janus kinase (Jak) signaling was frequently found altered. Anti-PD-1 or anti-PD-L1 monoclonal antibodies can reverse this immune checkpoint, releasing the brake on T-cell responses. The characterization of the mechanisms regulating both the expression of PD-1 and PD-L and their function(s) in HL is ongoing. We provide in this review the recent findings focused on this aim with special attention on the major research topics, such as adverse events and resistance to PD-1&ndash;PD-L1 inhibitor treatment, together with a part about angiogenesis, extracellular vesicles, and microbiome in HL pathogenesis

The seed nuclear proteome

OPEN ACCESS Cette revue date de 2010 mini review article Repetto, Ombretta : ex UMR LEG 0102, n'a jamais intégré l'UMR Agro Present adress : CRO, IRCCS, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico - Proteomics Core Facility, Experimental and Clinical Pharmacology, Aviano PN, Italie. BAP GEAPSI CT2International audienceUnderstanding the regulatory networks coordinating seed development will help to manipulate seed traits, such as protein content and seed weight, in order to increase yield and seed nutritional value of important food crops, such as legumes. Because of the cardinal role of the nucleus in gene expression, sub-proteome analyses of nuclei from developing seeds were conducted, taking advantage of the sequences available for model species. In this review, we discuss the strategies used to separate and identify the nuclear proteins at a stage when the seed is preparing for reserve accumulation. We present how these data provide an insight into the complexity and distinctive features of the seed nuclear proteome. We discuss the presence of chromatin-modifying enzymes and proteins that have roles in RNA-directed DNA methylation and which may be involved in modifying genome architecture in preparation for seed filling. Specific features of the seed nuclei at the transition between the stage of cell divisions and that of cell expansion and reserve deposition are described here which may help to manipulate seed quality traits, such as seed weight