Serum Proteome Of Patients Research Articles

Oxidative Stress, Persistent Inflammation and Blood Coagulation Alterations in Serum Proteome of Patients with Neovascular Age-Related Macular Degeneration.

Neovascular age-related macular degeneration (AMD) is a major cause of irreversible blindness in elderly populations in developed countries. AMD's etiopathology is multifactorial, with strong environmental and genetic components, but the exact molecular pathomechanisms underlying the disease are still unknown. In this study, we analyzed blood serum collected from 74 neovascular AMD patients and 58 healthy controls to identify proteins that may serve as potential biomarkers and expand our knowledge about the etiopathogenesis of the disease. The study revealed 17 differentially expressed proteins-11 up-regulated and 6 down-regulated-in neovascular AMD, which are involved in the biological processes previously linked with the disease-oxidative stress and persistent inflammation, impaired cellular transport, lipid metabolism and blood coagulation. In conclusion, the differences in the expressions of the proteins identified in this study may contribute to our understanding of the mechanisms underlying AMD and possibly serve in future as promising biomarkers.

Proteomics identifies complement protein signatures in patients with alcohol-associated hepatitis.

Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), creating an unmet need to identify noninvasive biomarkers for AH. In murine models, complement contributes to ethanol-induced liver injury. Therefore, we hypothesized that complement proteins could be rational diagnostic/prognostic biomarkers in AH. Here, we performed a comparative analysis of data derived from human hepatic and serum proteome to identify and characterize complement protein signatures in severe AH (sAH). The quantity of multiple complement proteins was perturbed in liver and serum proteome of patients with sAH. Multiple complement proteins differentiated patients with sAH from those with alcohol cirrhosis (AC) or alcohol use disorder (AUD) and healthy controls (HCs). Serum collectin 11 and C1q binding protein were strongly associated with sAH and exhibited good discriminatory performance among patients with sAH, AC, or AUD and HCs. Furthermore, complement component receptor 1-like protein was negatively associated with pro-inflammatory cytokines. Additionally, lower serum MBL associated serine protease 1 and coagulation factor II independently predicted 90-day mortality. In summary, meta-analysis of proteomic profiles from liver and circulation revealed complement protein signatures of sAH, highlighting a complex perturbation of complement and identifying potential diagnostic and prognostic biomarkers for patients with sAH.

Proteomics analysis of serum from thymoma patients

Thymoma is the most common malignant tumor in thymic epithelial tumors (TETS). This study aimed to identify the changes in serum proteomics in patients with thymoma. Proteins were extracted from twenty patients with thymoma serum and nine healthy controls and prepared for mass spectrometry (MS) analysis. Data independent acquisition (DIA) quantitative proteomics technique was used to examine the serum proteome. Differential proteins of abundance changes in the serum were identified. Bioinformatics was used to examine the differential proteins. Functional tagging and enrichment analysis were conducted using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The string database was used to assess the interaction of different proteins. In all, 486 proteins were found in all samples. There were differences in 58 serum proteins between patients and healthy blood donors, 35 up-regulated and 23 down-regulated. These proteins are primarily exocrine and serum membrane proteins involved in controlling immunological responses and antigen binding, according to GO functional annotation. KEGG functional annotation showed that these proteins play a significant role in the complement and coagulation cascade and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signal pathway. Notably, the KEGG pathway (complement and coagulation cascade) is enriched, and three key activators were up-regulated: von willebrand factor (VWF), coagulation factor v (F5) and vitamin k-dependent protein c (PC). Protein–protein interaction (PPI) analysis showed that six proteins ((VWF, F5, thrombin reactive protein 1 (THBS1), mannose-binding lectin-associated serine protease 2 (MASP2), apolipoprotein B (APOB), and apolipoprotein (a) (LPA)) were up-regulated and two proteins (Metalloproteinase inhibitor 1(TIMP1), ferritin light chain (FTL)) were down-regulated. The results of this study showed that several proteins involved in complement and coagulation cascades were up-regulated in the serum of patients.

Serum Proteomics in Patients with Head and Neck Cancer: Peripheral Blood Immune Response to Treatment.

In this real-world study, the aims were to prospectively evaluate the expression of inflammatory proteins in serum collected from head and neck cancer patients before and after treatment, and to assess whether there were differences in expression associated with treatment modalities. The mixed study cohort consisted of 180 patients with head and neck cancer. The most common tumor sites were the oropharynx (n = 81), the oral cavity (n = 53), and the larynx (n = 22). Blood tests for proteomics analysis were carried out before treatment, 7 weeks after the start of treatment, and 3 and 12 months after the termination of treatment. Sera were analyzed for 83 proteins using an immuno-oncology biomarker panel (Olink, Uppsala, Sweden). Patients were divided into four treatment groups: surgery alone (Surg group, n = 24), radiotherapy with or without surgery (RT group, n = 94), radiotherapy with concomitant cisplatin (CRT group, n = 47), and radiotherapy with concomitant targeted therapy (RT Cetux group, n = 15). For the overall cohort, the expression levels of 15 of the 83 proteins changed significantly between the pretreatment sample and the sample taken 7 weeks after the start of treatment. At 7 weeks after the start of treatment, 13 proteins showed lower expression in the CRT group compared to the RT group. The majority of the inflammatory proteins had returned to their pretreatment levels after 12 months. It was clearly demonstrated that cisplatin-based chemoradiation has immunological effects in patients with head and neck cancer. This analysis draws attention to several inflammatory proteins that are of interest for further studies.

Identification and Evaluation of Serum Protein BiomarkersThat Differentiate Psoriatic Arthritis From Rheumatoid Arthritis.

To identify serum protein biomarkers that might distinguish patients with early inflammatory arthritis (IA) with psoriatic arthritis (PsA) from those with rheumatoid arthritis (RA) and may be used to support appropriate early intervention. The serum proteome of patients with PsA and patients with RA was interrogated using nano-liquid chromatography mass spectrometry (nano-LC-MS/MS) (n = 64 patients), an aptamer-based assay (SomaScan) targeting 1,129 proteins (n = 36 patients), and a multiplexed antibody assay (Luminex) for 48 proteins (n = 64 patients). Multiple reaction monitoring (MRM) assays were developed to evaluate the performance of putative markers using the discovery cohort (n = 60 patients) and subsequently an independent cohort of PsA and RA patients (n = 167). Multivariate machine learning analysis of the protein discovery data from the 3 platforms revealed that it was possible to differentiate PsA patients from RA patients with an area under the curve (AUC) of 0.94 for nano-LC-MS/MS, 0.69 for bead-based immunoassay measurements, and 0.73 for aptamer-based analysis. Subsequently, in the separate verification and evaluation studies, random forest models revealed that a subset of proteins measured by MRM could differentiate PsA and RA patients with AUCs of 0.79 and 0.85, respectively. We present a serum protein biomarker panel that can separate patients with early-onset IA with PsA from those with RA. With continued evaluation and refinement using additional and larger patient cohorts, including those with other arthropathies, we suggest that the panel identified here could contribute to improved clinical decision making.

Effect of Mongolian medicine Sugmule-7 on serum proteomics in patients with ovarian senescence.

Effect of Mongolian medicine Sugmule-7 on serum proteomics in patients with ovarian senescence.

Serum proteome assessment in nonalcoholic fatty liver disease in children: a preliminary study

ABSTRACT Objectives Nonalcoholic fatty disease (NAFLD) affects 3–10% of the pediatric population, making it the most common chronic liver disease among children. The aim of the study is to identify potential biomarkers enabling the diagnosis of NAFLD and monitoring the course of the disease. Methods Proteome analysis was performed in a group of 30 patients (19 boys and 11 girls) in total, of whom 16 children had previously diagnosed NAFLD based on the abdominal ultrasound after excluding other diseases of this organ. Results A total of 297 proteins have been identified. Thirty-seven proteins (responsible for inflammation, stress response, and regulation of this process) differentiating both experimental groups were identified. Up-regulated proteins included afamin, retinol-binding protein-4, complement components, and hemopexin; while serum protease inhibitors, clusterin, immunoglobulin chains, and vitamin D binding protein were found in the down-regulated group. The correlation between selected proteins and indicators of noninvasive assessment of liver fibrosis (APRI, FIB-4) as well as differences between the serum proteome of patients with normal weight, overweight, and obesity were also assessed. Conclusion The plasma protein profile is significantly altered in nonalcoholic liver disease in children and may prove to be a valuable source of biomarkers to evaluate the extent of liver disease.

P44: Potential serum biomarkers for polycystic ovary syndrome by serum proteomics in patients with insulin resistance

American Journal of Reproductive ImmunologyVolume 80, Issue S1 p. 77-77 ABSTRACTS P44: Potential serum biomarkers for polycystic ovary syndrome by serum proteomics in patients with insulin resistance First published: 26 June 2018 https://doi.org/10.1111/aji.43_12984Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume80, IssueS1Special Issue: American-Sino Joint Meeting of Reproductive Immunology (ASRI-CSI 2018), June 28-1 July, 2018 Shanghai, ChinaJune 2018Pages 77-77 RelatedInformation

Serum Proteome in a Sporadic Amyotrophic Lateral Sclerosis Geographical Cluster.

This study is meant to characterize the serum proteome in a small geographical cluster of sporadic ALS subjects originating from a restricted geographical area and sharing the same environmental exposure, in a broader context of evaluating the relevance of environmental factors to disease onset, status, and progression. An Artificial Neural Network based software is used to compare the relative abundance of proteins identified as different (by means of bi-dimensional electrophoresis and mass spectrometry) in the serum proteome of patients and age-matched healthy controls. The patient's group is characterized by altered levels of acute phase reactants and of proteins involved in lipid homeostasis, along with over-representation of the APOE*4 allele. Characterization of the serum proteome in a small cluster of sporadic ALS patients, originating from a geographically restricted area with a high prevalence of the disease and evaluation of the results with software based on artificial neural networks, highlights the association of the relative abundance of some proteins (most notably, acute phase reactants and lipid homeostasis proteins) with the disease presence and status.

A Proteome-Derived Longitudinal Pharmacodynamic Biomarker for Diffuse Systemic Sclerosis Skin

In this study we systematically investigated alterations in the serum proteome of patients with diffuse cutaneous systemic sclerosis and identified differentially expressed proteins that correlated with disease severity. Our goal was to identify a combination of serum proteins that would provide a biological measure for the extent of skin disease and that could be combined into a longitudinal pharmacodynamic biomarker. We found that 16% of the sera proteins analyzed by SOMAscan aptamer technology, from two cohorts of patients with diffuse cutaneous systemic sclerosis, were identified as differentially regulated between diffuse cutaneous systemic sclerosis and controls and correlated with modified Rodnan skin score. This dataset showed tumor necrosis factor-α, IFN-γ, transforming growth factor-β, and IL-13 as potential upstream regulators of the serum protein patterns in the sera of patients with diffuse cutaneous systemic sclerosis. By ELISA, two analytes (ST2 and Spondin-1) best described longitudinal change in modified Rodnan skin score, using linear mixed models. This model was then validated in three independent cohorts. In this study we discovered a large array of proteins not previously associated with systemic sclerosis that provide insight into pathogenesis and potential targets for therapeutic intervention. Furthermore, we show that two of these proteins can be combined to form a robust longitudinal biomarker that might be used in clinical trials to assess changes in diffuse cutaneous systemic sclerosis skin disease over time.

Characterization of the Serum Proteome in Patients with Malignant Intraductal Papillary Mucinous Neoplasm

Characterization of the Serum Proteome in Patients with Malignant Intraductal Papillary Mucinous Neoplasm

Characterization of serum proteome in patients with metastatic colorectal cancer responsive and nonresponsive to bevacizumab using 2 d-DIGE.

484 Background: Treatment of patients with metastatic colorectal cancer includes chemotherapy and a monoclonal antibody (cetuximab or bevacizumab). Patients who have k-ras mutated tumors are given bevacizumab. However, no biomarker exists to determine those patients who will respond to this targeted treatment. The objective of this study was to investigate the differential protein expression between patients who do and do not respond to bevacizumab and also compare this with normal controls. Methods: Serum from 24 patients diagnosed with metastatic colorectal cancer and 11 normal controls were collected pre-treatment. All patients received bevacizumab along with chemotherapy. Progression free and overall survival data was collected on all patients. Serum was depleted of high abundant proteins and protein expression analysed using fluorescence two-dimensional differential in-gel electrophoresis (2 D-DIGE). Gels were scanned using a Typhoon 9410 Variable Mode Imager (GE Healthcare) and exported into Progenesis SameSpots v3.3 (Nonlinear Dynamics, UK) for quantitative analysis. Selected differentially expressed were excised, digested with trypsin and analysed using the LTQ-Orbitrap XL mass spectrometer. Results: 66 proteins were identified to be statistically expressed between the responders and non-responding group (p<0.05). 30 proteins were differentially expressed between the cancer and normal group (p<0.05). Conclusions: There is a significant difference in protein expression patterns between responders and non responders to bevacizumab. Further screening required to assess for instability proteins that may have functional importance in governing treatment resistance.

Serum proteomics in patients with diagnosis of abdominal aortic aneurysm

Molecular mechanisms underlying abdominal aneurysm (AAA) formation and rupture are not well understood. Early detection and repair of AAA may reduce the high mortality rates associated with rupture. Serum proteomics allows the detection of alterations in the expression of proteins, guiding further studies on these target molecules as potential markers. Analysis of proteomic profile of asymptomatic patients with AAA allows the identification of reliable predictors or markers of disease presence or progression. A proteomics approach based on two-dimensional electrophoresis and mass spectrometry was used to compare serum proteomic profiles of patients with AAA who are candidates for surgical repair compared with healthy controls. We analyzed in parallel the proteomic profile of subjects with cardiac heart failure to discriminate these two pathologies, which show similar pattern of systemic inflammation process. We identified in AAA subjects four serum proteins that show altered expression profile and that could be specifically linked to AAA pathology. We discuss the role of our identified proteins with their possible implications in disease outcome. This approach could provide an initial screening tool that may drive the basis for further research in the field of cardiovascular diseases. These results need to be validated in larger studies to find potential markers of AAA presence or progression to use in clinical settings. A proteomics approach was used to compare serum proteomic profiles of patients with abdominal aortic aneurysm who are candidates for surgical repair compared with healthy controls. Four serum proteins showed altered expression profile that could be correlated with the pathology. This approach could provide an initial screening tool that may drive the basis for further research in the field of cardiovascular diseases.

Serum Proteome of Patients with Systemic Sclerosis: Molecular Analysis of Expression and Prevalence of Haptoglobin Alpha Chain Isoforms

Haptoglobin (Hpt) is an acute phase protein characterized by three major phenotypes (Hpt 1-1, Hpt 2-1 and Hpt 2-2). The Hpt 2-2 phenotype is associated with increased prevalence of various systemic diseases, including autoimmune disorders. Moreover, the Hpt 2-2 phenotype induces a shift from Th1 to Th2 response and increases fibrotic processes. On this basis, we performed serum proteomic analysis of patients with Systemic Sclerosis (SSc), a connective tissue disorder associated with Th2-type immune response and characterized by interstitial and perivascular fibrosis due to different factors (including genetic, environmental, immunological and microchimeric factors). Serum of 23 SSc outpatients patients (4 males, 19 females, mean age 54+-5.3 years) diagnosed according to the American Rheumatism Association (ARA) criteria, were considered for the proteomic analysis and compared to serum of 21 control subjects. Serum depleted of HAP was analyzed by 2-DE, and Hpt chain spots were identified by WB. The expression frequency of each Hpt α chain in SSc patients and controls was compared and quantitative analysis of spot expression (percent Vol) was performed. Above all,, our study amplifies the limited data in the literature on proteomic analysis in SSc, also confirming previous data that revealed a significant increase of haptoglobin type 2-2 and a concomitant decrease of the 1-1 phenotype in SSc patients. Moreover, our results demonstrate that c spots are more prevalent in SSc patients than in controls (91.3% vs 55.5%, p<0.05), while the expression frequency of a and b spots does not change. In patients Hpt 2-1 or Hpt 1-1 e spot is less abundant. According to our results, the c and e spots can be considered markers for SSc and thus be of use for the early diagnosis of connective tissue disorders and in establishing appropriate treatment.

Abstract 5158: Serological autoantibody profiling in bladder cancer using protein arrays

Abstract Cancer cells might release at least part of their contents into the blood stream directly or through extracellular fluids upon cell damage or death. Cancer proteins not present in non-neoplastic cell subpopulations might then elicit a host immune response. The serum autoantibody repertoire from cancer patients might therefore, be exploited for the identification of tumor-associated antigens (TAAs). The recognition that human tumors stimulate the production of autoantibodies against such autologous cellular proteins (TAAs) has opened the door to the possibility that autoantibodies could be translated into serological tools for early diagnosis and/or disease management. In this report, we attempt at exploring the serum proteome of patients with bladder cancer using protein arrays. The serum autoantibody profiles of 18 patients with bladder cancer and 6 control specimens including cases affected with other neoplasias, benign urological diseases and healthy individuals was investigated using protein arrays containing more than 12,000 proteins. Data analyses included T-test as well as clustering strategies using the Prospector and CIMMiner softwares. Supervised clustered heatmaps served to highlight identified biological differences among autoantibody profiles arrays of bladder cancer cases and controls. Moreover, protein expression patterns of the identified immunogenic TAAs were assessed by immunohistochemistry on tissue microarrays (n=92). Supervised clustering analysis segregated bladder cancer patients from controls. A panel of 171 autoantibodies was identified to be differentially expressed in bladder cancer patients as compared to control individuals in a significant manner. Bladder cancer TAAs included proteins involved in cell proliferation, signal transduction, apoptosis, DNA-binding and transcription factors, among others. Immunohistochemical analyses on tissue arrays served to validate the increased protein expression of identified TAAs in bladder tumors. Moreover they revealed the relevance of expression patterns of proteins such as clusterin for bladder cancer diagnostics, staging and outcome prognosis. Protein expression patterns of clusterin were significantly associated with clinico-pathological variables such as tumor size (P=0.034), T1 substaging (P=0.013) or progression into muscle invasive disease (P=0.020). Thus, the novel application of high-throughput protein arrays for serum autoantibody profiling is providing critical information not only to identify TAAs candidate biomarkers for bladder cancer diagnostics and potential immunological therapeutic targets, such as clusterin, but also to further characterize bladder cancer progression.

Changes in the Serum Proteome of Patients with Sepsis and Septic Shock

Sepsis is still the leading cause of death in the intensive care unit. Our goal was to elucidate potential early differences in serum between survivors (SURV) and non-survivors (NON-SURV) on day 28. We applied proteomic technology to serum samples of patients with sepsis and septic shock. Serum samples from 18 patients with sepsis and septic shock were obtained during the first 12 h after diagnosis of septic shock. Patients were grouped into SURV and NON-SURV on day 28. Seven patients survived and 11 patients died. Using proteome analysis, two-dimensional gel electrophoresis detected more than 200 spots per gel. A differential protein expression was discovered between SURV and NON-SURV, whereby protein alterations not yet described in sepsis were revealed. Our results show that proteomic profiling is a useful approach for detecting protein expression dynamics in septic patients, and may bring us closer to achieving a comprehensive molecular profiling compared with genetic studies alone.

Serum Proteome to Predict Virologic Response in Patients With Hepatitis C Treated by Pegylated Interferon Plus Ribavirin

Surface-enhanced laser desorption ionization time-of-flight mass spectrometry is a proteomic technique that enables the global profiling of proteins. We used this approach to monitor the kinetics of serum proteome in patients with chronic hepatitis C virus infection receiving a standard bitherapy regimen to predict treatment response. Ninety-six patients with chronic hepatitis C were retrospectively selected. All patients received complete treatment with pegylated interferon in combination with ribavirin. Patients had serum sampling before starting treatment and at the end of treatment. Results were validated in an independent cohort of 51 patients. Comparison of protein profiles in pretreatment and after-treatment serum allowed us to characterize 50 protein peaks, the level of which significantly varied. In the group of patients with sustained virologic response, 37 peaks displayed significant variation during treatment, whereas only one peak differed in nonresponders. A logistic regression analysis allowed us to define an algorithm composed of 2 protein peaks (fibrosis stage and genotype) that correctly predicted, in pretreatment serum, response to treatment in 89% of all patients with an area under the receiver operating characteristic curve of 0.92. In the independent testing group, the same difference in proteome kinetics was observed between sustained responders and nonresponders. The algorithm correctly predicted treatment response in 81% of patients in the testing group. This study suggests that the kinetics of proteome are significantly different in serum of patients according to treatment response. Serum protein profiling allows prediction of response to antiviral treatment in a significant proportion of patients.