Clinical proteomics最新文献

{"title":"Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis.","authors":"Elena Moreno, Sergio Ciordia, Santos Milhano Fátima, Daniel Jiménez, Javier Martínez-Sanz, Pilar Vizcarra, Raquel Ron, Matilde Sánchez-Conde, Rafael Bargiela, Sergio Sanchez-Carrillo, Santiago Moreno, Fernando Corrales, Manuel Ferrer, Sergio Serrano-Villar","doi":"10.1186/s12014-024-09482-9","DOIUrl":"10.1186/s12014-024-09482-9","url":null,"abstract":"<p><strong>Background: </strong>Information on the microbiome's human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied a unique collection of samples harvested from April to June 2020 from unvaccinated patients.</p><p><strong>Methods: </strong>We compared 10 infected and hospitalized patients with severe (n = 5) and moderate (n = 5) coronavirus disease (COVID-19) with 10 uninfected individuals, including non-COVID-19 but susceptible individuals (n = 5) and non-COVID-19 and nonsusceptible healthcare workers with repeated high-risk exposures (n = 5).</p><p><strong>Results: </strong>By performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤ 0.05) out of 3376 unambiguously identified proteins (false discovery rate ≤ 1%). Major differences were observed between the non-COVID-19 and nonsusceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with the saliva of SARS-CoV-2-infected patients (p-value ≤ 0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression levels of two human proteins related to protein transport in the cytoplasm, DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that were overrepresented in the infected group.</p><p><strong>Conclusion: </strong>Our study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility, although further studies in larger cohorts will be necessary.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11112864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aqueous humor proteomics analyzed by bioinformatics and machine learning in PDR cases versus controls.","authors":"Tan Wang, Huan Chen, Ningning Li, Bao Zhang, Hanyi Min","doi":"10.1186/s12014-024-09481-w","DOIUrl":"10.1186/s12014-024-09481-w","url":null,"abstract":"<p><strong>Background: </strong>To comprehend the complexities of pathophysiological mechanisms and molecular events that contribute to proliferative diabetic retinopathy (PDR) and evaluate the diagnostic value of aqueous humor (AH) in monitoring the onset of PDR.</p><p><strong>Methods: </strong>A cohort containing 16 PDR and 10 cataract patients and another validation cohort containing 8 PDR and 4 cataract patients were studied. AH was collected and subjected to proteomics analyses. Bioinformatics analysis and a machine learning-based pipeline called inference of biomolecular combinations with minimal bias were used to explore the functional relevance, hub proteins, and biomarkers.</p><p><strong>Results: </strong>Deep profiling of AH proteomes revealed several insights. First, the combination of SIAE, SEMA7A, GNS, and IGKV3D-15 and the combination of ATP6AP1, SPARCL1, and SERPINA7 could serve as surrogate protein biomarkers for monitoring PDR progression. Second, ALB, FN1, ACTB, SERPINA1, C3, and VTN acted as hub proteins in the profiling of AH proteomes. SERPINA1 was the protein with the highest correlation coefficient not only for BCVA but also for the duration of diabetes. Third, \"Complement and coagulation cascades\" was an important pathway for PDR development.</p><p><strong>Conclusions: </strong>AH proteomics provides stable and accurate biomarkers for early warning and diagnosis of PDR. This study provides a deep understanding of the molecular mechanisms of PDR and a rich resource for optimizing PDR management.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between small-cell lung cancer serum protein/peptides determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and chemotherapy efficacy.","authors":"Zhihua Li, Junnan Chen, Bin Xu, Wei Zhao, Haoran Zha, Yalin Han, Wennan Shen, Yuemei Dong, Nan Zhao, Manze Zhang, Kun He, Zhaoxia Li, Xiaoqing Liu","doi":"10.1186/s12014-024-09483-8","DOIUrl":"10.1186/s12014-024-09483-8","url":null,"abstract":"<p><strong>Background: </strong>Currently, no effective measures are available to predict the curative efficacy of small-cell lung cancer (SCLC) chemotherapy. We expect to develop a method for effectively predicting the SCLC chemotherapy efficacy and prognosis in clinical practice in order to offer more pertinent therapeutic protocols for individual patients.</p><p><strong>Methods: </strong>We adopted matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and ClinPro Tools system to detect serum samples from 154 SCLC patients with different curative efficacy of standard chemotherapy and analyze the different peptides/proteins of SCLC patients to discover predictive tumor markers related to chemotherapy efficacy. Ten peptide/protein peaks were significantly different in the two groups.</p><p><strong>Results: </strong>A genetic algorithm model consisting of four peptides/proteins was developed from the training group to separate patients with different chemotherapy efficacies. Among them, three peptides/proteins (m/z 3323.35, 6649.03 and 6451.08) showed high expression in the disease progression group, whereas the peptide/protein at m/z 4283.18 was highly expressed in the disease response group. The classifier exhibited an accuracy of 91.4% (53/58) in the validation group. The survival analysis showed that the median progression-free survival (PFS) of 30 SCLC patients in disease response group was 9.0 months; in 28 cases in disease progression group, the median PFS was 3.0 months, a statistically significant difference (χ² = 46.98, P < 0.001). The median overall survival (OS) of the two groups was 13.0 months and 7.0 months, a statistically significant difference (χ² = 40.64, P < 0.001).</p><p><strong>Conclusions: </strong>These peptides/proteins may be used as potential biological markers for prediction of the curative efficacy and prognosis for SCLC patients treated with standard regimen chemotherapy.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a proteomic signature coupled with the kidney failure risk equation in predicting end stage kidney disease in a chronic kidney disease cohort.","authors":"Carlos Raúl Ramírez Medina, Ibrahim Ali, Ivona Baricevic-Jones, Moin A Saleem, Anthony D Whetton, Philip A Kalra, Nophar Geifman","doi":"10.1186/s12014-024-09486-5","DOIUrl":"10.1186/s12014-024-09486-5","url":null,"abstract":"<p><strong>Background: </strong>The early identification of patients at high-risk for end-stage renal disease (ESRD) is essential for providing optimal care and implementing targeted prevention strategies. While the Kidney Failure Risk Equation (KFRE) offers a more accurate prediction of ESRD risk compared to static eGFR-based thresholds, it does not provide insights into the patient-specific biological mechanisms that drive ESRD. This study focused on evaluating the effectiveness of KFRE in a UK-based advanced chronic kidney disease (CKD) cohort and investigating whether the integration of a proteomic signature could enhance 5-year ESRD prediction.</p><p><strong>Methods: </strong>Using the Salford Kidney Study biobank, a UK-based prospective cohort of over 3000 non-dialysis CKD patients, 433 patients met our inclusion criteria: a minimum of four eGFR measurements over a two-year period and a linear eGFR trajectory. Plasma samples were obtained and analysed for novel proteomic signals using SWATH-Mass-Spectrometry. The 4-variable UK-calibrated KFRE was calculated for each patient based on their baseline clinical characteristics. Boruta machine learning algorithm was used for the selection of proteins most contributing to differentiation between patient groups. Logistic regression was employed for estimation of ESRD prediction by (1) proteomic features; (2) KFRE; and (3) proteomic features alongside KFRE.</p><p><strong>Results: </strong>SWATH maps with 943 quantified proteins were generated and investigated in tandem with available clinical data to identify potential progression biomarkers. We identified a set of proteins (SPTA1, MYL6 and C6) that, when used alongside the 4-variable UK-KFRE, improved the prediction of 5-year risk of ESRD (AUC = 0.75 vs AUC = 0.70). Functional enrichment analysis revealed Rho GTPases and regulation of the actin cytoskeleton pathways to be statistically significant, inferring their role in kidney function and the pathogenesis of renal disease.</p><p><strong>Conclusions: </strong>Proteins SPTA1, MYL6 and C6, when used alongside the 4-variable UK-KFRE achieve an improved performance when predicting a 5-year risk of ESRD. Specific pathways implicated in the pathogenesis of podocyte dysfunction were also identified, which could serve as potential therapeutic targets. The findings of our study carry implications for comprehending the involvement of the Rho family GTPases in the pathophysiology of kidney disease, advancing our understanding of the proteomic factors influencing susceptibility to renal damage.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11102163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A reduced proteomic signature in critically ill Covid-19 patients determined with plasma antibody micro-array and machine learning.","authors":"Maitray A Patel, Mark Daley, Logan R Van Nynatten, Marat Slessarev, Gediminas Cepinskas, Douglas D Fraser","doi":"10.1186/s12014-024-09488-3","DOIUrl":"10.1186/s12014-024-09488-3","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 is a complex, multi-system disease with varying severity and symptoms. Identifying changes in critically ill COVID-19 patients' proteomes enables a better understanding of markers associated with susceptibility, symptoms, and treatment. We performed plasma antibody microarray and machine learning analyses to identify novel proteins of COVID-19.</p><p><strong>Methods: </strong>A case-control study comparing the concentration of 2000 plasma proteins in age- and sex-matched COVID-19 inpatients, non-COVID-19 sepsis controls, and healthy control subjects. Machine learning was used to identify a unique proteome signature in COVID-19 patients. Protein expression was correlated with clinically relevant variables and analyzed for temporal changes over hospitalization days 1, 3, 7, and 10. Expert-curated protein expression information was analyzed with Natural language processing (NLP) to determine organ- and cell-specific expression.</p><p><strong>Results: </strong>Machine learning identified a 28-protein model that accurately differentiated COVID-19 patients from ICU non-COVID-19 patients (accuracy = 0.89, AUC = 1.00, F1 = 0.89) and healthy controls (accuracy = 0.89, AUC = 1.00, F1 = 0.88). An optimal nine-protein model (PF4V1, NUCB1, CrkL, SerpinD1, Fen1, GATA-4, ProSAAS, PARK7, and NET1) maintained high classification ability. Specific proteins correlated with hemoglobin, coagulation factors, hypertension, and high-flow nasal cannula intervention (P < 0.01). Time-course analysis of the 28 leading proteins demonstrated no significant temporal changes within the COVID-19 cohort. NLP analysis identified multi-system expression of the key proteins, with the digestive and nervous systems being the leading systems.</p><p><strong>Conclusions: </strong>The plasma proteome of critically ill COVID-19 patients was distinguishable from that of non-COVID-19 sepsis controls and healthy control subjects. The leading 28 proteins and their subset of 9 proteins yielded accurate classification models and are expressed in multiple organ systems. The identified COVID-19 proteomic signature helps elucidate COVID-19 pathophysiology and may guide future COVID-19 treatment development.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics.","authors":"Sudipa Maity, Yuanyu Huang, Mitchell D Kilgore, Abbigail N Thurmon, Lee O Vaasjo, Maria J Galazo, Xiaojiang Xu, Jing Cao, Xiaoying Wang, Bo Ning, Ning Liu, Jia Fan","doi":"10.1186/s12014-024-09485-6","DOIUrl":"10.1186/s12014-024-09485-6","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) often results in diverse molecular responses, challenging traditional proteomic studies that measure average changes at tissue levels and fail to capture the complexity and heterogeneity of the affected tissues. Spatial proteomics offers a solution by providing insights into sub-region-specific alterations within tissues. This study focuses on the hippocampal sub-regions, analyzing proteomic expression profiles in mice at the acute (1 day) and subacute (7 days) phases of post-TBI to understand subregion-specific vulnerabilities and long-term consequences.</p><p><strong>Methods: </strong>Three mice brains were collected from each group, including Sham, 1-day post-TBI and 7-day post-TBI. Hippocampal subregions were extracted using Laser Microdissection (LMD) and subsequently analyzed by label-free quantitative proteomics.</p><p><strong>Results: </strong>The spatial analysis reveals region-specific protein abundance changes, highlighting the elevation of FN1, LGALS3BP, HP, and MUG-1 in the stratum moleculare (SM), suggesting potential immune cell enrichment post-TBI. Notably, established markers of chronic traumatic encephalopathy, IGHM and B2M, exhibit specific upregulation in the dentate gyrus bottom (DG2) independent of direct mechanical injury. Metabolic pathway analysis identifies disturbances in glucose and lipid metabolism, coupled with activated cholesterol synthesis pathways enriched in SM at 7-Day post-TBI and subsequently in deeper DG1 and DG2 suggesting a role in neurogenesis and the onset of recovery. Coordinated activation of neuroglia and microtubule dynamics in DG2 suggest recovery mechanisms in less affected regions. Cluster analysis revealed spatial variations post-TBI, indicative of dysregulated neuronal plasticity and neurogenesis and further predisposition to neurological disorders. TBI-induced protein upregulation (MUG-1, PZP, GFAP, TJP, STAT-1, and CD44) across hippocampal sub-regions indicates shared molecular responses and links to neurological disorders. Spatial variations were demonstrated by proteins dysregulated in both or either of the time-points exclusively in each subregion (ELAVL2, CLIC1 in PL, CD44 and MUG-1 in SM, and SHOC2, LGALS3 in DG).</p><p><strong>Conclusions: </strong>Utilizing advanced spatial proteomics techniques, the study unveils the dynamic molecular responses in distinct hippocampal subregions post-TBI. It uncovers region-specific vulnerabilities and dysregulated neuronal processes, and potential recovery-related pathways that contribute to our understanding of TBI's neurological consequences and provides valuable insights for biomarker discovery and therapeutic targets.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Kinome and phosphoproteome reprogramming underlies the aberrant immune responses in critically ill COVID-19 patients","authors":"Tomonori Kaneko, Sally Ezra, Rober Abdo, Courtney Voss, Shanshan Zhong, Xuguang Liu, Owen Hovey, Marat Slessarev, Logan Robert Van Nynatten, Mingliang Ye, Douglas D. Fraser, Shawn Shun‑Cheng Li","doi":"10.1186/s12014-024-09484-7","DOIUrl":"https://doi.org/10.1186/s12014-024-09484-7","url":null,"abstract":"<p><b>Correction: Clinical Proteomics (2024) 21:13</b> <b>https://doi.org/10.1186/s12014-024-09457-w</b></p><p>Following publication of the original article [1], the authors identified an error in the author name of Douglas D. Fraser.</p><p>The incorrect author name is: Douglas Fraser.</p><p>The correct author name is: Douglas D. Fraser.</p><p>The author group has been updated above and the original article [1] has been corrected.</p><ol data-track-component=\"outbound reference\"><li data-counter=\"1.\"><p>Kaneko T, Ezra S, Abdo R, Voss C, Zhong S, Liu X, Hovey O, Slessarev M, Van Nynatten LR, Ye M, Fraser DD, Li SS-C. Kinome and phosphoproteome reprogramming underlies the aberrant immune responses in critically ill COVID-19 patients. Clin Proteom. 2024;21:13. https://doi.org/10.1186/s12014-024-09457-w.</p><p>Article CAS Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><span>Author notes</span><ol><li><p>Sally Ezra, Rober Abdo and Courtney Voss have contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Department of Biochemistry, Western University, London, ON, N6A 5C1, Canada</p><p>Tomonori Kaneko, Sally Ezra, Courtney Voss, Shanshan Zhong, Xuguang Liu, Owen Hovey &amp; Shawn Shun‑Cheng Li</p></li><li><p>Department of Pathology and Laboratory Medicine, Western University, London, Canada</p><p>Rober Abdo</p></li><li><p>Departments of Medicine and Pediatrics, Western University, London, Canada</p><p>Marat Slessarev, Logan Robert Van Nynatten &amp; Douglas D. Fraser</p></li><li><p>CAS Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R&amp;A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian, 116023, China</p><p>Mingliang Ye</p></li><li><p>Lawson Health Research Institute, 750 Base Line Rd E, London, ON, N6C 2R5, Canada</p><p>Douglas D. Fraser</p></li></ol><span>Authors</span><ol><li><span>Tomonori Kaneko</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Sally Ezra</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Rober Abdo</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Courtney Voss</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Shanshan Zhong</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Xuguang Liu</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplex proteomics identifies inflammation-related plasma biomarkers for aging and cardio-metabolic disorders","authors":"Siting Wu, Yulin Li, Xue Zhao, Fu-Dong Shi, Jingshan Chen","doi":"10.1186/s12014-024-09480-x","DOIUrl":"https://doi.org/10.1186/s12014-024-09480-x","url":null,"abstract":"","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140678043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas","authors":"Haidong Deng, Ting Lei, Siqi Liu, Wenzhe Hao, Mengqing Hu, Xin Xiang, Ling Ye, Dongting Chen, Yan Li, Fangjun Liu","doi":"10.1186/s12014-024-09479-4","DOIUrl":"https://doi.org/10.1186/s12014-024-09479-4","url":null,"abstract":"Adamantinomatous craniopharyngiomas (ACPs) are rare benign epithelial tumours with high recurrence and poor prognosis. Biological differences between recurrent and primary ACPs that may be associated with disease recurrence and treatment have yet to be evaluated at the proteomic level. In this study, we aimed to determine the proteomic profiles of paired recurrent and primary ACP, gain biological insight into ACP recurrence, and identify potential targets for ACP treatment. Patients with ACP (n = 15) or Rathke’s cleft cyst (RCC; n = 7) who underwent surgery at Sanbo Brain Hospital, Capital Medical University, Beijing, China and received pathological confirmation of ACP or RCC were enrolled in this study. We conducted a proteomic analysis to investigate the characteristics of primary ACP, paired recurrent ACP, and RCC. Western blotting was used to validate our proteomic results and assess the expression of key tumour-associated proteins in recurrent and primary ACPs. Flow cytometry was performed to evaluate the exhaustion of tumour-infiltrating lymphocytes (TILs) in primary and recurrent ACP tissue samples. Immunohistochemical staining for CD3 and PD-L1 was conducted to determine differences in T-cell infiltration and the expression of immunosuppressive molecules between paired primary and recurrent ACP samples. The bioinformatics analysis showed that proteins differentially expressed between recurrent and primary ACPs were significantly associated with extracellular matrix organisation and interleukin signalling. Cathepsin K, which was upregulated in recurrent ACP compared with that in primary ACP, may play a role in ACP recurrence. High infiltration of T cells and exhaustion of TILs were revealed by the flow cytometry analysis of ACP. This study provides a preliminary description of the proteomic differences between primary ACP, recurrent ACP, and RCC. Our findings serve as a resource for craniopharyngioma researchers and may ultimately expand existing knowledge of recurrent ACP and benefit clinical practice.","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140603276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteomic characterization of colorectal cancer patients with FOLFOX chemotherapy by integrated proteomics technology","authors":"Xi Wang, Keren Zhang, Wan He, Luobin Zhang, Biwei Gao, Ruijun Tian, Ruilian Xu","doi":"10.1186/s12014-024-09454-z","DOIUrl":"https://doi.org/10.1186/s12014-024-09454-z","url":null,"abstract":"Colorectal Cancer (CRC) is a prevalent form of cancer, and the effectiveness of the main postoperative chemotherapy treatment, FOLFOX, varies among patients. In this study, we aimed to identify potential biomarkers for predicting the prognosis of CRC patients treated with FOLFOX through plasma proteomic characterization. Using a fully integrated sample preparation technology SISPROT-based proteomics workflow, we achieved deep proteome coverage and trained a machine learning model from a discovery cohort of 90 CRC patients to differentiate FOLFOX-sensitive and FOLFOX-resistant patients. The model was then validated by targeted proteomics on an independent test cohort of 26 patients. We achieved deep proteome coverage of 831 protein groups in total and 536 protein groups in average for non-depleted plasma from CRC patients by using a Orbitrap Exploris 240 with moderate sensitivity. Our results revealed distinct molecular changes in FOLFOX-sensitive and FOLFOX-resistant patients. We confidently identified known prognostic biomarkers for colorectal cancer, such as S100A4, LGALS1, and FABP5. The classifier based on the biomarker panel demonstrated a promised AUC value of 0.908 with 93% accuracy. Additionally, we established a protein panel to predict FOLFOX effectiveness, and several proteins within the panel were validated using targeted proteomic methods. Our study sheds light on the pathways affected in CRC patients treated with FOLFOX chemotherapy and identifies potential biomarkers that could be valuable for prognosis prediction. Our findings showed the potential of mass spectrometry-based proteomics and machine learning as an unbiased and systematic approach for discovering biomarkers in CRC.","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140595949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}