Cancer Genomics & Proteomics[JOURNAL]
Sun
200 papers
Tape stripped stratum corneum samples are suitable for diagnosis and comprehensive proteomic investigation in mycosis fungoides.
Qureshi HA, Azimi A, Wells J … +1 more , Fernandez-Penas P
Proteomics Clin Appl · 2023 May · PMID 36824058 · Publisher ↗
BACKGROUND: Mycosis Fungoides (MF) is a common cutaneous T-cell lymphoma. It can sometimes be challenging to diagnose MF using current clinico-histopathological criteria. Non-invasive molecular profiling analysis has the...
BACKGROUND: Mycosis Fungoides (MF) is a common cutaneous T-cell lymphoma. It can sometimes be challenging to diagnose MF using current clinico-histopathological criteria. Non-invasive molecular profiling analysis has the potential to aid the diagnosis and understanding of MF. METHOD: Lesional and body site matched normal stratum corneum samples were obtained from the same MF patients (n = 28) using adhesive discs, followed by proteomic analyses using data-independent acquisition mass spectrometry (DIA-MS). Differential abundance analyses and bioinformatic analyses were performed to identify differentially abundant proteins and altered biofunctions between the MF and normal stratum corneum samples. RESULTS: In total, 1303 proteins were identified, of which 290 proteins were significantly changed in the MF cohort compared to the normal stratum corneum. Ingenuity pathway analysis (IPA) predicted the significant inhibition of cell death of cancer cells and significant activation of immune-related activities and viral infection in the MF lesions. MF lesions were also associated with upstream regulators relating to immuno-oncologic dysfunctions. The top-250 variating proteins efficiently separated normal stratum corneum from matched MF samples. CONCLUSION: Non-invasive proteomic analysis could transform the diagnosis of MF by reducing the need for invasive biopsy. The identification of altered biological functions may serve as useful biomarkers to predict MF progression.
Quantitative proteomic analysis of bronchoalveolar lavage fluids from patients with small cell lung cancers.
Vu HM, Mohammad HB, Nguyen TNC … +5 more , Lee JH, Do Y, Sung JY, Lee SH, Kim MS
Proteomics Clin Appl · 2023 Sep · PMID 36807835 · Publisher ↗
PURPOSE: Small cell lung cancer (SCLC) is one of the malignant cancers with aggressive progression and poor prognosis. Bronchoalveolar lavage fluid (BALF) has been arising recently as a potential source of biomarkers for...
PURPOSE: Small cell lung cancer (SCLC) is one of the malignant cancers with aggressive progression and poor prognosis. Bronchoalveolar lavage fluid (BALF) has been arising recently as a potential source of biomarkers for lung cancers. In this study, we performed quantitative BALF proteomic analysis to identify potential biomarkers for SCLC. EXPERIMENTAL DESIGN: BALF were collected from tumor-bearing lungs and non-tumor lungs of five SCLC patients. Then, BALF proteomes were prepared for a TMT-based quantitative mass spectrometry analysis. Differentially expressed proteins (DEP) were identified when considering individual variation. Potential SCLC biomarker candidates were validated by immunohistochemistry (IHC). A public database of multiple SCLC cell lines was used to evaluate the correlation of these markers with SCLC subtypes and chemo-drug responses. RESULTS: We identified 460 BALF proteins in SCLC patients and observed considerable individual variation among the patients. Immunohistochemical analysis and bioinformatics resulted in the identification of CNDP2 and RNPEP as potential subtype markers for ASCL1 and NEUROD1, respectively. In addition, CNDP2 was found to be positively correlated with responses to etoposide, carboplatin, and irinotecan. CONCLUSIONS AND CLINICAL RELEVANCE: BALF is an emerging source of biomarkers, making it useful for the diagnosis and prognosis of lung cancers. We characterized the proteomes of paired BALF samples collected from tumor-bearing and non-tumor lungs of SCLC patients. Several proteins were found elevated in tumor-bearing BALF, and especially CNDP2 and RNPEP appeared to be potential indicators for ASLC1-high and NEUROD1-high subtypes of SCLC, respectively. The positive correlation of CNDP2 with chemo-drug responses would help to make decisions for treatment of SCLC patients. These putative biomarkers could be comprehensively investigated for a clinical use towards precision medicine.
Identification of PRTN3 as a novel biomarker for the diagnosis of early gastric cance.
Guo D, Zhang B, Wu D … +2 more , Hu X, Tu H
J Proteomics · 2023 Apr · PMID 36804624 · Publisher ↗
Gastric cancer (GC) remains one of the most common types of cancer worldwide and has a high mortality rate. However, tools for the early detection of gastric cancer are still lacking. Isobaric tagging for relative and ab...
Gastric cancer (GC) remains one of the most common types of cancer worldwide and has a high mortality rate. However, tools for the early detection of gastric cancer are still lacking. Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic assays were conducted to identify and quantify the differentially expressed proteins (DEPs) in the gastric mucosal tissues of GC patients at different stages. Bioinformatics analysis was used to identify the pathways enriched among the DEPs and candidate marker proteins. The expression levels and distribution of candidate proteins were confirmed by parallel reaction monitoring (PRM) analysis. In this study, by using the iTRAQ quantitative proteomic strategy, we identified 727 and 502 DEPs that were upregulated in EGC vs. PGC and EGC vs. NGC, respectively. These DEPs were mainly involved in the innate immune response and RNA binding. PRTN3 was identified as a marker of early gastric cancer by Gene Ontology enrichment analysis. Furthermore, the PRM assay confirmed the significant overexpression of PRTN3 in EGC gastric mucosa compared to PGC and NGC mucosa. Our data demonstrated that PRTN3 in the gastric mucosa could be used as a novel biomarker to identify patients with early gastric cancer via endoscopy. SIGNIFICANCE: Gastric cancer remains one of the most common types of cancer worldwide and has a high mortality rate. Patients with progressive gastric cancer and gastroesophageal junction cancer have a poor prognosis, with a 5-year relative survival rate of 6%. Therefore, early detection and diagnosis of gastric cancer is a key step toward improving the survival rate. The present study identified PRTN3 as a marker of early gastric cancer by an iTRAQ quantitative proteomic strategy. The PRM assay confirmed the significant overexpression of PRTN3 in EGC gastric mucosa compared to PGC and NGC mucosa. This study discovered that PRTN3 in the gastric mucosa could be used as a novel biomarker to identify patients with early gastric cancer via endoscopy.
Applying single-cell highly multiplexed secretome proteomics to characterize immunotherapeutic products and predict clinical responses.
Ni W, Han EX, Cyr M … +2 more , Mackay S, Zhou J
Proteomics · 2023 Jul · PMID 36786585 · Publisher ↗
Genetically and phenotypically identical immune cell populations can be highly heterogenous in terms of their immune functions and protein secretion profiles. The microfluidic chip-based single-cell highly multiplexed se...
Genetically and phenotypically identical immune cell populations can be highly heterogenous in terms of their immune functions and protein secretion profiles. The microfluidic chip-based single-cell highly multiplexed secretome proteomics enables characterization of cellular heterogeneity of immune responses at different cellular and molecular layers. Increasing evidence has demonstrated that polyfunctional T cells that simultaneously produce 2+ proteins per cell at the single-cell level are key effector cells that contribute to the development of potent and durable cellular immunity against pathogens and cancers. The functional proteomic technology offers a wide spectrum of cellular function assessment and can uniquely define highly polyfunctional cell subsets with cytokine signatures from live individual cells. This high-dimensional single-cell analysis provides deep dissection into functional heterogeneity and helps identify predictive biomarkers and potential correlates that are crucial for immunotherapeutic product design optimization and personalized immunotherapy development to achieve better clinical outcomes.
Oncoproteomic profiling of AML: moving beyond genomics.
Joshi SK, Tognon CE, Druker BJ … +1 more , Rodland KD
Expert Rev Proteomics · 2022 · PMID 36734985 · Full text
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PARP inhibitor olaparib induced differential protein expression in cervical cancer cells.
Rajawat J, Awasthi P, Banerjee M
J Proteomics · 2023 Mar · PMID 36646275 · Publisher ↗
PARP inhibitors are a potential class of chemotherapeutic drugs but PARP inhibitor response has not been explored systematically. We lack a specific understanding of the subset of the proteome preferentially modified in...
PARP inhibitors are a potential class of chemotherapeutic drugs but PARP inhibitor response has not been explored systematically. We lack a specific understanding of the subset of the proteome preferentially modified in various cancers by PARP inhibitors. Implications of PARP inhibitor and PARP1 in cervical cancer treatment and resistance are not fully elucidated. We conducted a mass spectrometry-based proteomic analysis of cervical cancer Hela cells treated with olaparib. We aimed to identify the alteration in the protein signaling pathway induced by PARP inhibitors beyond the DNA damage response pathway. Our data demonstrate a significant reduction in PARP activity and enhanced cell death after olaparib treatment. We further observed articulated proteomic changes with a significant enrichment of proteins in diverse cellular processes. The differentially expressed proteins were predominantly associated with RNA metabolism, mRNA splicing, processing, and RNA binding. Our data also identified proteins that could probably contribute to survival mechanisms resulting in resistance to PARP inhibitors. Hence, we put forth the overview of proteomic changes induced by PARP inhibitor olaparib in cervical cancer cells. This study highlights the significant proteins modified during PARP inhibition and thus could be a probable target for combination therapies with PARP inhibitors in cervical cancer. SIGNIFICANCE.
Serum proteomics profiling identifies a preliminary signature for the diagnosis of early-stage lung cancer.
Gasparri R, Noberini R, Cuomo A … +9 more , Yadav A, Tricarico D, Salvetto C, Maisonneuve P, Caminiti V, Sedda G, Sabalic A, Bonaldi T, Spaggiari L
Proteomics Clin Appl · 2023 Mar · PMID 36645712 · Publisher ↗
PURPOSE: Lung cancer is the most common cause of death from cancer worldwide, largely due to late diagnosis. Thus, there is an urgent need to develop new approaches to improve the detection of early-stage lung cancer, wh...
PURPOSE: Lung cancer is the most common cause of death from cancer worldwide, largely due to late diagnosis. Thus, there is an urgent need to develop new approaches to improve the detection of early-stage lung cancer, which would greatly improve patient survival. EXPERIMENTAL DESIGN: The quantitative protein expression profiles of microvesicles isolated from the sera from 46 lung cancer patients and 41 high-risk non-cancer subjects were obtained using a mass spectrometry method based on a peptide library matching approach. RESULTS: We identified 33 differentially expressed proteins that allow discriminating the two groups. We also built a machine learning model based on serum protein expression profiles that can correctly classify the majority of lung cancer cases and that highlighted a decrease in the levels of Arysulfatase A (ARSA) as the most discriminating factor found in tumors. CONCLUSIONS AND CLINICAL RELEVANCE: Our study identified a preliminary, non-invasive protein signature able to discriminate with high specificity and selectivity early-stage lung cancer patients from high-risk healthy subjects. These results provide the basis for future validation studies for the development of a non-invasive diagnostic tool for lung cancer.
Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.
Hong H, Chen X, Wang H … +3 more , Gu X, Yuan Y, Zhang Z
Proteomics · 2023 May · PMID 36625413 · Publisher ↗
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, often metastasizes to the lungs. The implications of lysine lactylation (Kla), a recently identified histone post-translational modification (...
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, often metastasizes to the lungs. The implications of lysine lactylation (Kla), a recently identified histone post-translational modification (PTM), in the pathology of HCC remain unclear. Here, we report the first proteomic survey of this specific modification in HCC (with no metastasis during 3 years of follow-up), normal liver tissues, and lung metastasis samples of HCC. Of the 2045 modification sites detected on 960 proteins, 1438 sites on 772 proteins contained quantitative information. Subsequently, we analyzed the differentially modified proteins among the different groups. Differentially lactylated proteins were found to be involved in several biological processes, including-but not limited to-amino acid metabolism, ribosomal protein synthesis, and fatty acid metabolism. In addition, we identified numerous highly valuable lactate-modified proteins from the literature. Among them, we verified the lactate modification levels of the following two tumor-related proteins and obtained similar results: USP14 and ABCF1. These two modified proteins will be further investigated in our future studies. This paper is the first report on the lactylome of HCC and it provides a reliable foundation for further research on Kla in HCC.
Combination of size-exclusion chromatography and ion exchange adsorption for improving the proteomic analysis of plasma-derived extracellular vesicles.
Wang Y, Zhang Y, Li Z … +6 more , Wei S, Chi X, Yan X, Lv H, Zhao L, Zhao L
Proteomics · 2023 May · PMID 36624553 · Publisher ↗
Extracellular vesicles (EVs) are lipid membrane vesicles released by live cells that carry a variety of biomolecules, including nucleic acids, lipids, and proteins. Recently, proteins in plasma-derived EVs have emerged a...
Extracellular vesicles (EVs) are lipid membrane vesicles released by live cells that carry a variety of biomolecules, including nucleic acids, lipids, and proteins. Recently, proteins in plasma-derived EVs have emerged as novel biomarkers with essential functions in the diagnosis and prognosis of human diseases. However, the current methods of isolating EVs from plasma often lead to coisolated impurities in biological fluids. Therefore, before performing any research protocol, the process of extracting EVs from plasma for proteomic analysis must be optimized. In this study, two EV isolation strategies, size exclusion chromatography (SEC) and SEC combined with ion exchange adsorption (SEC + IEA), were compared in terms of the purity and quantity of protein in EVs. Our results demonstrated that, compared to single-step SEC, SEC combined with IEA could produce plasma-derived EVs with a higher purity by decreasing the abundance of lipoprotein. Additionally, with MS analysis, we demonstrated that the combination approach maintained the stability and improved the purity of EVs in many plasma samples. Furthermore, by combining SEC with IEA, more cancer-associated proteins were detected in the plasma of various cancer samples.
Proteoglycans in breast cancer, identification and characterization by LC-MS/MS assisted proteomics approach: A review.
Kizhakkeppurath Kumaran A, Sahu A, Singh A … +4 more , Aynikkattil Ravindran N, Sekhar Chatterjee N, Mathew S, Verma S
Proteomics Clin Appl · 2023 Jul · PMID 36598116 · Publisher ↗
PURPOSE: Proteoglycans (PGs) are negatively charged macromolecules containing a core protein and single or several glycosaminoglycan chains attached by covalent bond. They are distributed in all tissues, including extrac...
PURPOSE: Proteoglycans (PGs) are negatively charged macromolecules containing a core protein and single or several glycosaminoglycan chains attached by covalent bond. They are distributed in all tissues, including extracellular matrix (ECM), cell surface, and basement membrane. They are involved in major pathways and cell signalling cascades which modulate several vital physiological functions of the body. They have also emerged as a target molecule for cancer treatment and as possible biomarkers for early cancer detection. Among cancers, breast cancer is a highly invasive and heterogenous type and has become the major cause of mortality especially among women. So, this review revisits the studies on PGs characterization in breast cancer using LC-MS/MS-based proteomics approach, which will be further helpful for identification of potential PGs-based biomarkers or therapeutic targets. EXPERIMENTAL DESIGN: There is a lack of comprehensive knowledge on the use of LC-MS/MS-based proteomics approaches to identify and characterize PGs in breast cancer. RESULTS: LC-MS/MS assisted PGs characterization in breast cancer revealed the vital PGs in breast cancer invasion and progression. In addition, comprehensive profiling and characterization of PGs in breast cancer are efficiently carried out by this approach. CONCLUSIONS: Proteomics techniques including LC-MS/MS-based identification of proteoglycans is effectively carried out in breast cancer research. Identification of expression at different stages of breast cancer is a major challenge, and LC-MS/MS-based profiling of PGs can boost novel strategies to treat breast cancer, which involve targeting PGs, and also aid early diagnosis using PGs as biomarkers.
Integrated proteomic and phosphoproteomic analysis for characterization of colorectal cancer.
Zhu H, Li Y, Guo J … +11 more , Feng S, Ge H, Gu C, Wang M, Nie R, Li N, Wang Y, Wang H, Zhong J, Qian X, He G
J Proteomics · 2023 Mar · PMID 36596410 · Publisher ↗
Proteins and translationally modified proteins like phosphoproteins have essential regulatory roles in tumorigenesis. This study attempts to elucidate the dysregulated proteins driving colorectal cancer (CRC). To explore...
Proteins and translationally modified proteins like phosphoproteins have essential regulatory roles in tumorigenesis. This study attempts to elucidate the dysregulated proteins driving colorectal cancer (CRC). To explore the differential proteins, we performed iTRAQ labeling proteomics and TMT labeling phosphoproteomics analysis of CRC tissues and adjacent non-cancerous tissues. The functions of quantified proteins were analyzed using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Subcellular localization analysis. Depending on the results, we identified 330 differential proteins and 82 phosphoproteins in CRC. GO and KEGG analyses demonstrated that protein changes were primarily associated with regulating biological and metabolic processes through binding to other molecules. Co-expression relationships between proteomic and phosphoproteomic analysis revealed that TMC5, SMC4, SLBP, VSIG2, and NDRG2 were significantly dysregulated differential proteins. Additionally, based on the predicted co-expression proteins, we identified that the stem-loop binding protein (SLBP) was up-regulated in CRC cells and promoted the proliferation and migration of CRC. This study reports an integrated proteomic and phosphoproteomic analysis of CRC to discern the functional impact of protein alterations and provides a candidate diagnostic biomarker or therapeutic target for CRC. SIGNIFICANCE: Combining one or more high-throughput omics technologies with bioinformatics to analyze biological samples and explore the links between biomolecules and their functions can provide more comprehensive and multi-level insights for disease mechanism research. Proteomics, phosphoproteomics, metabolomics and their combined analysis play an important role in the auxiliary diagnosis, the discovery of biomarkers and novel therapeutic targets for colorectal cancer. In this integrated proteomic and phosphoproteomic analysis, we identified proteins and phosphoproteins in colorectal cancer tissue and analyzed potential mechanisms contributing to progression in colorectal cancer. The results of this study provide a foundation to focus future experiments on the contribution of altered protein and phosphorylation patterns to prevention and treatment of colorectal cancer.
Developing quantitative assays for six urinary glycoproteins using parallel reaction monitoring, data-independent acquisition, and TMT-based data-dependent acquisition.
Ponce S, Zhang H
Proteomics · 2023 Apr · PMID 36592098 · Publisher ↗
Quantitative approaches encompassing parallel reaction monitoring (PRM), data-independent acquisition (DIA), and data-dependent acquisition (DDA) are commonly used to investigate protein expression profiles. However, ana...
Quantitative approaches encompassing parallel reaction monitoring (PRM), data-independent acquisition (DIA), and data-dependent acquisition (DDA) are commonly used to investigate protein expression profiles. However, analytical performances of assays developed using PRM, DIA, and Tandem Mass Tag (TMT)-based DDA for quantitative proteomics have yet not been investigated. Here, we developed assays for glycopeptides identified from six glycoproteins, including Leucine-rich alpha-2-glycoprotein (LRG1), Prostaglandin-H2 D-isomerase (PTGDS), Aminopeptidase N (ANPEP), CD63 antigen (CD63), Clusterin (CLU), and Prostatic acid phosphatase (ACPP), using PRM, DDA, and DIA and evaluated the analytical performances of each assay using the different acquisition modes. We also compared assays in each acquisition mode on three different orbitrap instruments: Thermo Fisher Q Exactive, Exploris 480, and Lumos. We found that DIA showed the largest linear range, highest sensitivity, and most reproducibility. We then applied our developed DIA assays to urine samples from non-aggressive (n = 48) and aggressive (n = 35) prostate cancer patients. In conclusion, we developed assays for the six glycoproteins, evaluated the analytical performances of each assay in DIA, PRM, and PRM acquisition modes on three types of mass spectrometry instruments, and chose the DIA assays for the quantitative analysis of urine samples from patients with aggressive and non-aggressive prostate cancer.
OSppc: A web server for online survival analysis using proteome of pan-cancers.
Zhang L, Wang Q, Han Y … +3 more , Huang Y, Chen T, Guo X
J Proteomics · 2023 Feb · PMID 36587732 · Publisher ↗
Prognostic biomarker, as a feasible and objective indicator, is valuable in the assessment of cancer risk. With the development of high-throughput sequencing technology, the screening of prognostic biomarkers has become...
Prognostic biomarker, as a feasible and objective indicator, is valuable in the assessment of cancer risk. With the development of high-throughput sequencing technology, the screening of prognostic biomarkers has become easy, but it is difficult to screen prognostic markers based on proteomic data. In this study we developed a tool named Online consensus Survival analysis web server based on Proteome of Pan-cancers, abbreviated as OSppc, to evaluate the prognostic values of protein biomarkers. >8000 cancer cases with proteomic data, transcriptomic data and clinical follow-up information were collected from TCGA and CPTAC. 14,038 proteins (including proteins and their phosphorylated forms) analyzed by reverse-phase protein arrays and mass spectrometry in 33 types of cancers were collected. In OSppc, three analysis modules are provided, including Survival Analysis, Differential Analysis and Correlation Analysis. Survival analysis module exhibits HR with 95% CI and KM curves with log-rank p value of protein and mRNA levels of input genes. Differential analysis module shows the box plots of protein expression levels in different tissues. Correlation analysis module provides scatter plot with pearson's and spearman's correlation coefficient of the protein and its corresponding mRNA. OSppc can be accessed at http://bioinfo.henu.edu.cn/Protein/OSppc.html. SIGNIFICANCE: OSppc can analyze the association between protein, mRNA and prognosis, the correlation between proteome data and gene expression profiles, the differential expression of proteome data between subgroups such as normal and cancer as well. OSppc is registration-free and very valuable to evaluate the prognostic potency of protein of interests. OSppc is very valuable for researchers and clinicians to screen, develop and validate potential protein prognostic biomarkers in pan-cancers, and offers the opportunities to investigate the clinical important functional genes and therapeutic targets of cancers.
Proteomics-based trapping with single or multiple inactive mutants reproducibly profiles histone deacetylase 1 substrates.
Herath KE, Kodikara IKM, Pflum MKH
J Proteomics · 2023 Mar · PMID 36587730 · Full text
Histone deacetylase 1 (HDAC1) plays a key role in diverse cellular processes. With the aberrant expression of HDAC1 linked to many diseases, including cancers, HDAC inhibitors have been used successfully as therapeutics....
Histone deacetylase 1 (HDAC1) plays a key role in diverse cellular processes. With the aberrant expression of HDAC1 linked to many diseases, including cancers, HDAC inhibitors have been used successfully as therapeutics. HDAC1 has been predominantly associated with histone deacetylation and gene expression. Recently, non-histone substrates have revealed diverse roles of HDAC1 beyond epigenetics. To augment discovery of non-histone substrates, we introduced "substrate trapping" to enrich HDAC1 substrates using an inactive mutant. Herein, we performed a series of proteomics studies to test the robustness of HDAC1 substrate trapping. Based on our recent results documenting that different HDAC1 mutants preferentially bound different substrates, which suggested that multiple mutants could be used for efficient trapping, trapping with three single point mutants simultaneously identified several potential substrates uniquely compared to a single mutant alone. However, a greater number of biologically interesting hits were observed using only a single mutant, which suggests that the C151A HDAC1 mutant is the optimal trap. Importantly, comparing independent trials with a single mutant performed by different experimentalists and HEK293 cell populations, trapping was robust and reproducible. Based on the reproducible trapping data, carnosine N-methyltransferase 1 (CARNMT1) was validated as an HDAC1 substrate. The data document that mutant trapping is an effective method for discovery of unanticipated HDAC substrates. SIGNIFICANCE: Histone deacetylase (HDAC) proteins are well established epigenetic transcriptional regulators that deacetylate histone substrates to control gene expression. More recently, deacetylation of non-histone substrates has linked HDAC activity to functions outside of epigenetics. Given the use of HDAC inhibitor drugs as anti-cancer therapeutics, understanding the full functions of HDAC proteins in cell biology is essential to future drug design. To discover unanticipated non-histone substrates and further characterize HDAC functions, inactive mutants have been used to "trap" putative substrates, which were identified with mass spectrometry-based proteomics analysis. Here multiple trapping studies were performed to test the robustness of using inactive mutants and proteomics for HDAC substrate discovery. The data confirm the value of trapping mutants as effective tools to discover HDAC substrates and link HDAC activity to unexpected biological functions.
Proteomic and phosphoproteomic landscape of salivary extracellular vesicles to assess OSCC therapeutical outcomes.
Sun J, Wang X, Ding Y … +8 more , Xiao B, Wang X, Ali MM, Ma L, Xie Z, Gu Z, Chen G, Tao WA
Proteomics · 2023 Mar · PMID 36573687 · Publisher ↗
Circulating extracellular vesicles (EVs) have emerged as an appealing source for surrogates to evaluate the disease status. Herein, we present a novel proteomic strategy to identify proteins and phosphoproteins from sali...
Circulating extracellular vesicles (EVs) have emerged as an appealing source for surrogates to evaluate the disease status. Herein, we present a novel proteomic strategy to identify proteins and phosphoproteins from salivary EVs to distinguish oral squamous cell carcinoma (OSCC) patients from healthy individuals and explore the feasibility to evaluate therapeutical outcomes. Bi-functionalized magnetic beads (BiMBs) with Ti (IV) ions and a lipid analog, 1,2-Distearoyl-3-sn-glycerophosphoethanolamine (DSPE) are developed to efficiently isolate EVs from small volume of saliva. In the discovery stage, label-free proteomics and phosphoproteomics quantification showed 315 upregulated proteins and 132 upregulated phosphoproteins in OSCC patients among more than 2500 EV proteins and 1000 EV phosphoproteins, respectively. We further applied targeted proteomics by coupling parallel reaction monitoring with parallel accumulation-serial fragmentation (prm-PASEF) to measure panels of proteins and phosphoproteins from salivary EVs collected before and after surgical resection. A panel of three total proteins and three phosphoproteins, most of which have previously been associated with OSCC and other cancer types, show sensitive response to the therapy in individual patients. Our study presents a novel strategy to the discovery of effective biomarkers for non-invasive assessment of OSCC surgical outcomes with small amount of saliva.
Identification of potential extracellular vesicle protein markers altered in osteosarcoma from public databases.
Zhang J, Li H
Proteomics Clin Appl · 2023 Jul · PMID 36571514 · Publisher ↗
PURPOSE: Extracellular vesicles (EVs) have become promising biomarkers for cancer management. Particularly, the molecular cargo such as proteins carried by EVs are similar to their cells of origin, providing important in...
PURPOSE: Extracellular vesicles (EVs) have become promising biomarkers for cancer management. Particularly, the molecular cargo such as proteins carried by EVs are similar to their cells of origin, providing important information that can be used for cancer diagnostics, prognosis, and treatment monitoring. However, to date, molecular analysis on EVs is still challenging, limited by the availability of efficient analytical technologies, largely due to the small size of EVs. In this work, we developed a computational workflow for in silico identification of potential EV protein markers from genomic and proteomic databases, and applied it for the discovery of osteosarcoma (OS) EV protein markers. EXPERIMENTAL DESIGN: Both mRNA and protein data were computed and compared from publicly accessible databases, and top markers with high differential expression levels were selected. RESULTS: Thirty nine markers were identified overexpressed and seven found to be downregulated. These identified markers have been found to be associated with OS on different aspects in literature, demonstrating the usability of this workflow. CONCLUSIONS AND CLINICAL RELEVANCE: This work provides a list of potential EV protein markers that are either overexpressed or downregulated in OS for further experimental validation for improved clinical management of OS.
Intraoperative plasma proteomic changes in cardiac surgery: In search of biomarkers of post-operative delirium.
Wiredu K, O'Connor S, Naseem H … +5 more , Brauer BL, Kettenbach AN, Frost HR, Shaefi S, Gerber SA
Proteomics Clin Appl · 2023 Jul · PMID 36567636 · Full text
PURPOSE: Delirium presents a significant healthcare burden. It complicates post-operative care in up to 50% of cardiac surgical patients with worse outcomes, longer hospital stays and higher cost of care. Moreover, the n...
PURPOSE: Delirium presents a significant healthcare burden. It complicates post-operative care in up to 50% of cardiac surgical patients with worse outcomes, longer hospital stays and higher cost of care. Moreover, the nature of delirium following cardiac surgery with cardiopulmonary bypass (CPB) remains unclear, the underlying pathobiology is poorly understood, status quo diagnostic methods are subjective, and diagnostic biomarkers are currently lacking. OBJECTIVE: To identify diagnostic biomarkers of delirium and for insights into possible neuronal pathomechanisms. EXPERIMENTAL DESIGN: Comparative proteomic analyses were performed on plasma samples from a nested matched cohort of patients who underwent cardiac surgery. Validation by targeted proteomics was performed in an independent set of samples. Biomarkers were assessed for biological functions and diagnostic accuracy. RESULTS: Forty-seven percent of subjects demonstrated delirium. Of 3803 proteins identified from patient samples by multiplexed quantitative proteomics, 16 were identified as signatures of exposure to CPB, and 11 biomarkers distinguished delirium cases from non-cases (AuROC = 93%). Notable among these biomarkers are C-reactive protein, serum amyloid A-1 and cathepsin-B. CONCLUSIONS AND CLINICAL RELEVANCE: The interplay of systemic and central inflammatory markers sheds new light on delirium pathogenesis. This work suggests that accurate identification of cases may be achievable using panels of biomarkers.
Proteomics-based scoring of cellular response to stimuli for improved characterization of signaling pathway activity.
Kazakova EM, Solovyeva EM, Levitsky LI … +6 more , Bubis JA, Emekeeva DD, Antonets AA, Nazarov AA, Gorshkov MV, Tarasova IA
Proteomics · 2023 Mar · PMID 36478387 · Publisher ↗
Omics technologies focus on uncovering the complex nature of molecular mechanisms in cells and organisms, including biomarkers and drug targets discovery. Aiming at these tasks, we see that information extracted from omi...
Omics technologies focus on uncovering the complex nature of molecular mechanisms in cells and organisms, including biomarkers and drug targets discovery. Aiming at these tasks, we see that information extracted from omics data is still underused. In particular, characteristics of differentially regulated molecules can be combined in a single score to quantify the signaling pathway activity. Such a metric can be useful for comprehensive data interpretation to follow: (1) developing molecular responses in time; (2) potency of a drug on a certain cell culture; (3) ranking the signaling pathway activity in stimulated cells; and (4) integration of the omics data and assay-based measurements of cell viability, cytotoxicity, and proliferation. With recent advances in ultrafast mass spectrometry for quantitative proteomics allowing data collection in a few minutes, proteomics score for cellular response to stimuli can become a fast, accurate, and informative complement to bioassays. Here, we utilized an interquartile-based selection of differentially regulated features and a variety of schemes for quantifying cellular responses to come up with the quantitative metric for total cellular response and pathway activity. Validation was performed using antiproliferative and virus assays and label-free proteomics data collected for cancer cells subjected to drug stimulation.
A peptide-centric approach to analyse quantitative proteomics data- an application to prostate cancer biomarker discovery.
Lima T, Rodrigues JE, Manadas B … +3 more , Henrique R, Fardilha M, Vitorino R
J Proteomics · 2023 Feb · PMID 36427804 · Publisher ↗
Bottom-up proteomics is a popular approach in molecular biomarker research. However, protein analysts have realized the limitations of protein-based approaches for identifying and quantifying proteins in complex samples,...
Bottom-up proteomics is a popular approach in molecular biomarker research. However, protein analysts have realized the limitations of protein-based approaches for identifying and quantifying proteins in complex samples, such as the identification of peptides sequences shared by multiple proteins and the difficulty in identifying modified peptides. Thus, there are many exciting opportunities to improve analysis methods. Here, an alternative method focused on peptide analysis is proposed as a complement to the conventional proteomics data analysis. To investigate this hypothesis, a peptide-centric approach was applied to reanalyse a urine proteome dataset of samples from prostate cancer patients and controls. The results were compared with the conventional protein-centric approach. The relevant proteins/peptides to discriminate the groups were detected based on two approaches, p-value and VIP values obtained by a PLS-DA model. A comparison of the two strategies revealed high inconsistency between protein and peptide information and greater involvement of peptides in key PCa processes. This peptide analysis unveiled discriminative features that are lost when proteins are analyzed as homogeneous entities. This type of analysis is innovative in PCa and integrated with the widely used protein-centric approach might provide a more comprehensive view of this disease and revolutionize biomarker discovery. SIGNIFICANCE: In this study, the application of a protein and peptide-centric approaches to reanalyse a urine proteome dataset from prostate cancer (PCa) patients and controls showed that many relevant proteins/peptides are missed by the conservative nature of p-value in statistical tests, therefore, the inclusion of variable selection methods in the analysis of the dataset reported in this work is fruitful. Comparison of protein- and peptide-based approaches revealed a high inconsistency between protein and peptide information and a greater involvement of peptides in key PCa processes. These results provide a new perspective to analyse proteomics data and detect relevant targets based on the integration of peptide and protein information. This data integration allows to unravel discriminative features that normally go unnoticed, to have a more comprehensive view of the disease pathophysiology and to open new avenues for the discovery of biomarkers.
Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells.
Xu X, Yin F, Guo M … +8 more , Gan G, Lin G, Wen C, Wang J, Song P, Wang J, Qi ZQ, Zhong CQ
Proteomics · 2023 Jan · PMID 36408942 · Publisher ↗
Exosomes derived from mesenchymal stem cells (MSCs) have been used for cancer treatment, however, an in-depth analysis of the exosomal proteomes is lacking. In this manuscript, we use the diaPASEF (parallel accumulation...
Exosomes derived from mesenchymal stem cells (MSCs) have been used for cancer treatment, however, an in-depth analysis of the exosomal proteomes is lacking. In this manuscript, we use the diaPASEF (parallel accumulation serial fragmentation combined with the data-independent acquisition) method to quantify exosomes derived from human umbilical cord mesenchymal stem cells (UCMSCs) and rat bone marrow stem cells (BMSCs), resulting in identification of 4200 human proteins and 5362 rat proteins. Comparison of human exosomal proteins and total cellular proteins reveals that some proteins exist in the exosomes exclusively that can be served as potential markers for exosomes. Quantitative proteomic analysis of exosomes from different passages of BMSCs shows that the proteins involved in TGF-β signaling pathway are regulated in abundance, which could be markers for the therapeutic ability of BMSC exosomes. Collectively, the data presented by this study can be a resource for further study of exosome research.
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