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At least 217 records · Page 12Linked to original sources
PubMed2026

Proteomic profiling reveals that DPP4 overexpression increases cell adhesion, inhibits cell migration, and restores androgen sensitivity in prostate cancer.

Dipeptidyl peptidase-4 (DPP4), a serine protease with both enzymatic and non-enzymatic roles, has emerged as a context-dependent modulator of tumor progression. In the present study, we investigated the expression and function of DPP4 in androgen-sensitive and castration-resistant prostate cancer (CRPC) models. Proteomic analysis of androgen-resistant prostate cells overexpressing DPP4 identified the involvement of the cellular adhesion molecules pathway. In prostate cells, lentiviral-mediated DPP4 overexpression restored androgen receptor signaling, inhibited epithelial-to-mesenchymal transition, and reduced cell migration, whereas DPP4 silencing produced the opposite effects. We demonstrate that DPP4 expression is down-regulated in CRPC cells and that treatment with capsaicin (CAP), a bioactive compound derived from red peppers, restores DPP4 expression. Moreover, DPP4 restoration by CAP suppresses prostate tumorigenesis in the TRAMP mice in vivo model of prostate cancer. Our results suggest that DPP4 could be a new target for CRPC.

Male↗
PubMed2006

Proteomic profiling of lipid droplet proteins in hepatoma cell lines expressing hepatitis C virus core protein.

Hepatitis C virus (HCV) core protein has been suggested to play crucial roles in the pathogeneses of liver steatosis and hepatocellular carcinomas due to HCV infection. Intracellular HCV core protein is localized mainly in lipid droplets, in which the core protein should exert its significant biological/pathological functions. In this study, we performed comparative proteomic analysis of lipid droplet proteins in core-expressing and non-expressing hepatoma cell lines. We identified 38 proteins in the lipid droplet fraction of core-expressing (Hep39) cells and 30 proteins in that of non-expressing (Hepswx) cells by 1-D-SDS-PAGE/MALDI-TOF mass spectrometry (MS) or direct nanoflow liquid chromatography-MS/MS. Interestingly, the lipid droplet fraction of Hep39 cells had an apparently lower content of adipose differentiation-related protein and a much higher content of TIP47 than that of Hepswx cells, suggesting the participation of the core protein in lipid droplet biogenesis in HCV-infected cells. Another distinct feature is that proteins involved in RNA metabolism, particularly DEAD box protein 1 and DEAD box protein 3, were detected in the lipid droplet fraction of Hep39 cells. These results suggest that lipid droplets containing HCV core protein may participate in the RNA metabolism of the host and/or HCV, affecting the pathopoiesis and/or virus replication/production in HCV-infected cells.

Cell Line↗
PubMed2025

Plasma Proteomic Profiles Predict Individual Future Osteoarthritis Risk.

OBJECTIVE: Osteoarthritis (OA) is a widespread degenerative joint disease that causes a considerable socioeconomic burden. Despite progress in genetic and environmental insights, early diagnosis is still limited by the lack of evident symptoms during the initial phases and accurate biomarkers. This study aims to identify plasma proteins associated with future risk of OA and develop a predictive model. METHODS: We conducted a large-scale proteomic analysis of 45,307 participants from the UK Biobank, excluding those with baseline OA. Plasma samples were assayed using the Olink Explore Proximity Extension Assay targeting 1,463 unique proteins. Clinical variables and OA outcomes were extracted and linked to electronic health records. A predictive model was constructed using the LightGBM machine learning method, and SHapley Additive exPlanations (SHAP) were applied to evaluate the importance of variables. RESULTS: We identified a panel of proteins significantly associated with the risk of developing OA. Notably, after adjusting for multiple confounders, collagen type IX alpha 1 chain (COL9A1) and cartilage acidic protein 1 (CRTAC1) were the most significant predictors of incident OA, with hazard ratios of 1.54 (95% confidence interval [CI] 1.48-1.61) and 1.65 (95% CI 1.54-1.78), respectively. SHAP analysis allowed a profound interpretation of the contribution of each protein and clinical variable to the model, revealing the multifactorial nature of OA risk prediction. The temporal trajectories of plasma proteins indicated that the levels of COL9A1 and CRTAC1 began to deviate from normal for more than a decade before OA onset, suggesting their potential use in early detection strategies. The predictive model, developed using the LightGBM algorithm, integrated proteins with clinical covariates and demonstrated an area under the curve (AUC) of 0.729 for 5-year OA prediction, 0.721 for 10-year prediction, and 0.723 for all incident OA. The predictive accuracy of the model was further enhanced for hip and knee OA, achieving AUCs of 0.820 and 0.803 for 5-year predictions. CONCLUSION: Our study identified the role of plasma proteomics in predicting future OA risk, which could contribute to preemptive measures. The innovative model, which integrates proteomic biomarkers with clinical data, offers a potential tool for risk assessment, potentially optimizing OA management strategies and enhancing prevention efforts.

Humans↗
PubMed2006

Mass spectrometric proteomics profiles of in vivo tumor secretomes: capillary ultrafiltration sampling of regressive tumor masses.

Identification of in vivo secreted peptides/proteins (secretomes) in tumor masses has the potential to provide important biomarkers and therapeutic targets for cancer therapy. However, limitations of existing technologies have made obtaining these secretomes for analysis extremely difficult. Here we employed an in vivo sampling technique using capillary ultrafiltration (CUF) probes to collect secretomes directly from tumor masses. Mass spectrometric proteomics approaches were then used to identify the tumor secretomes. A UV-induced skin fibrosarcoma cell line (UV-2240) was subcutaneously injected into C3H/NeH mice, resulting in tumor masses that initially progressed, then regressed and eventually eradicated. We then implanted CUF probes into tumor masses at the progressive and regressive stage. Five secreted proteins (cyclophilin-A, S100A4, profilin-1, thymosin beta 4 and 10), previously associated with tumor progression, were identified from tumor masses at the progressive stage. Five secreted proteins including three protease inhibitors (fetuin-A, alpha-1 antitrypsin 1-6, and contrapsin) were identified from tumor masses at the regressive stage. The technique involving CUF probes linked to mass spectrometric proteomics reinforces systems biology studies of cell-cell interactions and is potentially applicable to the discovery of in vivo biomarkers in human disease.

Animals↗
PubMed2025

Phospho-proteome profiling in human neurons reveals targets of TBK1 in ALS/FTD-associated autophagy networks.

Loss-of-function variants in TBK1, encoding a protein kinase, are strongly associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, how haploinsufficiency for TBK1 leads to age-related neurodegeneration remains unresolved. Here, we utilize sets of isogenic induced pluripotent stem cells (iPSCs) with loss of TBK1 or loss of optineurin (OPTN) for quantitative global proteomics and phospho-proteomics in both stem cells and excitatory neurons. We found that TBK1 sustains the abundance and phosphorylation of its interacting adapter proteins, AZI2/NAP1, TANK, and TBKBP1/SINTBAD. Moreover, TBK1 regulates the phosphorylation of endo-lysosomal proteins, such as GABARAPL2, the late-endosome GTPase RAB7A, and selective autophagy cargo receptor proteins-including novel phospho-sites in p62/SQSTM1-in neurons. Finally, we provide a census of the phospho-proteome in nascent human neurons for further studies. Overall, TBK1 serves as a point of convergence in ALS/FTD-linked endo-lysosomal networks that act in a cell-autonomous manner to maintain protein homeostasis in neurons.

Humans↗
PubMed2026

Proteomic profiling of cephalic vein reveals potential biomarkers for arteriovenous fistula neointimal hyperplasia in ESRD patients.

Arteriovenous fistula (AVF) is the preferred vascular access for patients with end-stage renal disease; however, its failure is primarily due to neointimal hyperplasia. Five patients who underwent initial AVF surgery served as the control group, and another five patients with failed AVF surgery served as the experimental group. Herein, we employed mass spectrometry (MS)-based quantitative proteomics coupled with tandem mass tag labeling to screen differentially expressed proteins (DEPs) in the anastomotic cephalic vein, followed by bioinformatics analyses and verification experiments. A total of 121 DEPs were identified in the failed AVF group. GO analysis was primarily enriched in protein binding, nucleic acid binding, enzyme binding, mRNA binding, cadherin binding, catalytic activity, and cell adhesion molecule binding. KEGG pathways were mainly enriched in cell aggregation and adhesion, actin cytoskeleton, extracellular matrix-receptor interaction, PI3K-Akt signaling pathway, complement and coagulation cascades, and cholesterol metabolism. Protein-protein interaction network consisted of 86 (71.07%) DEPs, including complement VII (C7), factor IX (F9), SERPINC1, microfibril-associated glycoprotein 4 (MFAP4), complement C1s subcomponent, complement C1q subcomponent subunit A, complement C1q subcomponent subunit B, tissue factor, and von Willebrand factor, which interacting with numerous other proteins. In the expanded validation for different patients, C7, F9, SERPINC1, and MFAP4, were verified by immunohistochemical staining and Western blotting, which were consistent with the proteomics results. Collectively, this study identifies a series of potential diagnostic biomarkers, and explores the underlying mechanisms associated with AVF dysfunction.

Humans↗
PubMed2025

High-Frequency Irreversible Electroporation Alters Proteomic Profiles and Tropism of Small Tumor-Derived Extracellular Vesicles to Promote Immune Cell Infiltration.

High-frequency irreversible electroporation (H-FIRE) is a nonthermal tumor ablation technique that disrupts the blood-brain barrier (BBB) in a focal and reversible manner. However, the mechanisms underlying this disruption remain poorly understood, particularly the role of small tumor-derived extracellular vesicles (sTDEVs) released from ablated tumor cells. In this study, we investigate the proteomic and functional alterations of sTDEVs released from F98 glioma and LL/2 Lewis lung carcinoma cells following H-FIRE ablation. Mass spectrometry analysis revealed 108 unique proteins in sTDEVs derived from ablative doses of H-FIRE, which are capable of disrupting the BBB in an in vitro model. Proteomic analysis of TDEVs highlights key changes in pathways related to integrin signaling, Platelet-derived growth factor receptor (PDGFR) signaling, and ubiquitination, which may underline their interactions with brain endothelial cells. These "disruptive" sTDEVs exhibit enhanced tropism for cerebral endothelial cells both in vitro and in vivo, where they persist in the brain longer than sTDEVs released after non-ablative H-FIRE doses. Notably, when introduced into a healthy Fischer rat model, disruptive sTDEVs are associated with increased recruitment of Iba1+ immune cells, suggesting a potential role in modulating post-ablation immune responses. However, despite their altered protein composition, these vesicles do not directly increase BBB permeability in vivo. This study is the first to demonstrate that electroporation-based tumor ablation significantly alters the composition and functionality of tumor-derived extracellular vesicles, potentially influencing the tumor microenvironment post-ablation. These findings have important implications for developing multimodal treatment strategies that combine H-FIRE with systemic therapies to enhance efficacy while managing the peritumoral microenvironment.

Animals↗
PubMed2004

Proteome profile changes during transdifferentiation of NRP-152 rat prostatic basal epithelial cells.

NRP-152 is an androgen responsive, non-tumorigenic cell line, which shows basal epithelial cell characteristics under normal growth conditions. It has been noted that NRP-152 undergoes morphological and cytoskeletal changes toward its luminal counterpart NRP-154 when it is grown under growth restrictive conditions. We have extensively investigated the details of protein change of NRP-152 during transdifferentiation using proteomic techniques. NRP-152 cells were cultured under normal and growth restrictive media conditions for 3, 5 days. NRP-154 cells were normally cultured. Protein samples were submitted to 2D gel electrophoresis and silver stained. Protein patterns on the gels were comparatively analysed using Melanie III software. Protein spots exhibiting significant changes in NRP-152 cells during the time course were excised and subjected to in-gel tryptic digestion. After 6 days of growth restrictive conditions in NRP-152, the cells were morphologically changed resembling luminal phenotype. Of the 35 protein spots that were up-reglated, 20 proteins from 21 spots were identified by peptide mass fingerprinting and, of 21 proteins spots that were down-regulated, 10 proteins from 12 spots were identified as landmark proteins. Our study confirmed that basal NRP-152 cells were proportionally transdifferentiated into luminal featuring cells according to the duration of growth restrictive culture conditions. This suggests that human prostatic basal epithelial cells may be changed into luminal cells under certain conditions. Proteomic approach enabled us to identify 30 proteins involved in this differentiation with a single experiment. These proteins will be subjected to further functional studies to evaluate their possible roles related to cellular differentiation. These data strongly support that proteomics is a very powerful approach for studying physiologic and pathologic cellular changes such as differentiation and carcinogenesis.

Animals↗
PubMed2026

Plasma Proteomic Profiling Identifies Candidate Biomarkers for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy that is often diagnosed after curative treatment is no longer feasible. Existing biomarkers, particularly CA19-9, have limited sensitivity and specificity. Plasma proteins that capture tumor-associated biological alterations may therefore provide useful signals for earlier detection. METHODS: Plasma samples from 99 patients with PDAC and 30 healthy controls were analyzed using data-independent acquisition (DIA) proteomics. Differentially expressed proteins were identified using predefined statistical thresholds and further examined by functional enrichment analysis. Selected candidate biomarkers were validated by ELISA in an independent subset. RESULTS: Among 565 quantified plasma proteins, 52 were differentially expressed between PDAC and controls. These proteins were enriched in extracellular processes, cholesterol metabolism, complement and coagulation cascades, and pancreatic secretion pathways. ELISA validation confirmed higher plasma levels of Cathepsin S, CTRB2, MARCO, PIGR, PRDX6, REG1A, Trypsin-2, and PEP-FAP in patients with PDAC compared with healthy controls. ROC analyses showed moderate-to-good discriminatory performance for several candidates, and the MARCO + PEP-FAP model improved classification compared with either marker alone. CONCLUSION: These findings reveal circulating proteins linked to key PDAC-related biological processes and identify eight candidates for further evaluation in multi-protein diagnostic panels. Larger validation studies incorporating clinically relevant disease control groups are warranted to determine their diagnostic specificity and clinical utility.

Humans↗
PubMed2026

Serum Proteomic Profiling Reveals Renin-Associated Immune and Cytoskeletal Dysregulation in Post-COVID-19 Condition Patients with Secondary Adrenal Insufficiency.

Post-COVID-19 condition (PCC) with secondary adrenal insufficiency (SAI) involves multiorgan dysfunction, potentially linked to renin-angiotensin-aldosterone system dysregulation. The molecular basis of renin-associated pathology remains unclear. Here, PCC+SAI patients were stratified by upright renin into low- (<38.8&#x202f;pg/mL) and high-renin (&#x2265;38.8&#x202f;pg/mL) groups. Clinical, endocrine, and proteomic analyses were performed. We found that high-renin patients showed increased BMI, lipids, renin, and aldosterone, but reduced aldosterone-to-renin ratio. Proteomic annalysis identified 20 differentially expressed proteins (DEPs), including 17 upregulated and 3 downregulated proteins in Ren-H patients. Functional annotation revealed that 15 DEPs were immune-related (e.g., APOC4, APOE, C4BPA, CFAH, CFHR3, PF4V, PLF4), while FLNA and COF1 represented cytoskeletal proteins. These DEPs were primarily involved in immune response, complement and coagulation cascades, and MAPK signaling pathways. Correlation analyses indicated that upright renin was positively correlated with complement-related proteins and platelet-derived immune factors, while cytoskeletal proteins (FLNA, COF1) showed positive associations with serum Na+ levels. Additionally, white blood cell and platelet counts were positively correlated with the majority of DEPs. In conclusion, exploratory proteomic analyses suggest that elevated upright renin in PCC+SAI may be associated with immune dysregulation, complement activation, and cytoskeletal remodeling, offering novel insights into the endocrine-immune interactions driving postviral sequelae.

Humans↗
PubMed2007

Quantitative proteomics profiling of sarcomere associated proteins in limb and extraocular muscle allotypes.

The sarcomere is the major structural and functional unit of striated muscle. Approximately 65 different proteins have been associated with the sarcomere, and their exact composition defines the speed, endurance, and biology of each individual muscle. Past analyses relied heavily on electrophoretic and immunohistochemical techniques, which only allow the analysis of a small fraction of proteins at a time. Here we introduce a quantitative label-free, shotgun proteomics approach to differentially quantitate sarcomeric proteins from microgram quantities of muscle tissue in a fast and reliable manner by liquid chromatography and mass spectrometry. The high sequence similarity of some sarcomeric proteins poses a problem for shotgun proteomics because of limitations in subsequent database search algorithms in the exclusive assignment of peptides to specific isoforms. Therefore multiple sequence alignments were generated to improve the identification of isoform specific peptides. This methodology was used to compare the sarcomeric proteome of the extraocular muscle allotype to limb muscle. Extraocular muscles are a unique group of highly specialized muscles with distinct biochemical, physiological, and pathological properties. We were able to quantitate 40 sarcomeric proteins; although the basic sarcomeric proteins in extraocular muscle are similar to those in limb muscle, key proteins stabilizing the connection of the Z-bands to thin filaments and the costamere are augmented in extraocular muscle and may represent an adaptation to the eccentric contractions known to normally occur during eye movements. Furthermore, a number of changes are seen that closely relate to the unique nature of extraocular muscle.

Animals↗
PubMed2006

Differential effects of two period genes on the physiology and proteomic profiles of mouse anterior tibialis muscles.

The molecular components that generate and maintain circadian rhythms of physiology and behavior in mammals are present both in the brain (suprachiasmatic nucleus; SCN) and in peripheral tissues. Examination of mice with targeted disruptions of either mPer1 or mPer2 has shown that these two genes have key roles in the SCN circadian clock. Here we show that loss of the clock gene mPer2 affects forced locomotor performance in mice without altering muscle contractility. A proteomic analysis revealed that the anterior tibialis muscles of the mPer2 knockout mice had higher levels of glycolytic enzymes such as triose phosphate isomerase and enolase than those of either the wild type or mPer1 knockout mice. In addition, the level of expression of HSP90 in the mPer2 mutant mice was also significantly higher than in wildtype mice. These results suggest that the reduced locomotor endurance of the mPer2 knockout mice reflects a greater dependence on anaerobic metabolism under stress conditions, and that the two canonical clock genes, mPer1 and mPer2, play distinct roles in the physiology of skeletal muscle.

Animals↗
PubMed2006

Proteomic profiling of rat bone marrow mesenchymal stem cells induced by 5-azacytidine.

Mesenchymal stem cells (MSCs) can differentiate into different types of cells and thus have tremendous potential for cell therapy and tissue engineering. 5-Azacytidine (5-aza), a DNA demethylation reagent, has been reported to induce MSCs to differentiate into cardiomyocytes in vitro. To determine a global effect of 5-aza on MSCs, we investigated the protein expressions of rat MSCs with two-dimensional gel electrophoresis (2-DE). We have generated a proteome reference map of rat MSCs, and have successfully identified 34 proteins with MALDI-TOF-MS analysis. Nine proteins showed distinct regulation in MSCs after 5-aza treatment. The proteins regulated by 5-aza included cytoskeletal proteins, cadmium-binding proteins, and metabolic proteins, etc. These proteins have been reported to be involved in cell proliferation and differentiation through different signaling pathways, and the molecular mechanism of MSCs differentiation is discussed at the proteome level.

Animals↗
PubMed2026

Blood-based proteomic profiling reveals context-dependent changes in BCL2-associated signaling during taxane therapy in breast cancer patients.

The quality of life for many cancer survivors is compromised due to severe, long-lasting side effects of chemotherapy. As part of a pilot, prospective, non-interventional study to examine the side effects of chemotherapy in breast cancer patients, we examined the change in protein expression in blood collected from patients before and after treatment with taxanes for 12&#x2009;weeks. Protein expression was measured with reverse phase proteomic arrays (RPPA), which revealed divergent changes in apoptosis, senescence, and calcium signaling-related proteins depending on treatment setting (neoadjuvant vs. adjuvant). The largest change identified was BCL2 (B-cell lymphoma 2), a founding member of the BCL2 family of proteins that regulate apoptosis. Other proteins regulated by BCL2, including RB1 (retinoblastoma protein 1) and NLRP3 (NLR family pyrin domain containing 3) changed significantly over the course of treatment. These differences are consistent with intracellular calcium signaling dysregulation and activation of stress-response pathways that overlap with senescent-associated secretory phenotype (SASP)-like signaling, which has been implicated in cancer recurrence. To contextualize these observations, we generated Kaplan-Meier survival curves using publicly available proteomics data from The Cancer Proteome Atlas (TCPA). This work aims to demonstrate how blood-based proteomics can serve as a non-invasive method to monitor systemic physiological shifts during cancer therapy, offering a framework for generating hypotheses about chemotherapy timing and long-term outcomes.

Humans↗
PubMed2005

Proteomic profiling of cellular proteins interacting with the hepatitis C virus core protein.

Hepatitis C virus (HCV) is a causative agent of chronic hepatitis and hepatocellular carcinoma. The core protein of HCV packages the viral RNA genome to form a nucleocapsid. In addition to its function as a structural protein, core protein is involved in regulation of cellular transcription, virus-induced transformation, and pathogenesis. To gain insights into cellular functions of the core protein by identification of cellular proteins interacting with the core protein, we employed a proteomic approach. Hepatocytes soluble cytoplasmic proteins were applied to the core proteins immobilized on Ni-nitrilotriacetic resin and total bound cellular proteins were resolved by 2-DE. Analyses of interacting proteins by matrix-assisted laser desorption/ionization-time of flight mass spectrometry allowed identification of 14 cellular proteins binding to the core protein. These proteins include DEAD-box polypeptide 5, similar in function to a known protein identified previously by yeast two-hybrid screening and 13 newly identified cellular proteins. Interestingly, nine protein spots were identified as intermediate microfilament proteins, including cytokeratins (five spots for cytokeratin 8, two for cytokeratin 19, and one for cytokeratin 18) and vimentin. Cytokeratin 8 and vimentin, which were previously shown to be involved in the infection processes of other viruses, were further analyzed to confirm their in vivo interactions with the core protein by immunoblotting and immunofluorescence microscopy. We discuss the functional implications of the interactions of the core protein with newly identified cellular proteins in HCV infection and pathogenesis.

Animals↗
PubMed2004

Informatics platform for global proteomic profiling and biomarker discovery using liquid chromatography-tandem mass spectrometry.

We have developed an integrated suite of algorithms, statistical methods, and computer applications to support large-scale LC-MS-based gel-free shotgun profiling of complex protein mixtures using basic experimental procedures. The programs automatically detect and quantify large numbers of peptide peaks in feature-rich ion mass chromatograms, compensate for spurious fluctuations in peptide signal intensities and retention times, and reliably match related peaks across many different datasets. Application of this toolkit markedly facilitates pattern recognition and biomarker discovery in global comparative proteomic studies, simplifying mechanistic investigation of physiological responses and the detection of proteomic signatures of disease.

Algorithms↗
PubMed2005

Distinct proteomic profiles of amphetamine self-administration transitional states.

In the rat, continuous access to d-amphetamine (d-AMPH) leads to lengthy bouts of self-administration, voluntary abstinence, and relapse to self-administration. Previous studies have revealed that the progression from psychostimulant self-administration to abstinence to relapse is mediated in part by the ventral hippocampus. Stimulation of the ventral subiculum (vSub) during voluntary abstinence from d-AMPH self-administration reinstates self-administration and increases nucleus accumbens (NAc) dopamine efflux. Quantitative proteomic examination of the hippocampus from rats naive to amphetamine, during a self-administration session 'Binge', during voluntarily abstinence 'Abstinent', and after reinstatement of self-administration 'Relapse', revealed a differential proteomic state during abstinence. Actin- and cytoskeletal-related proteins were over-represented in the changes occurring during abstinence and suggest a decrease in actin filament polymerization. These changes may underlie alterations in neuronal tone during abstinence that could affect both neurotransmission and behavior. These data provide the first classification of addiction-related behaviors based on clustering of quantitative proteomic measurements. .

Actins↗