Clinical proteomics最新文献

{"title":"Histology-resolved proteomics reveals distinct tumor and stromal profiles in low- and high-grade prostate cancer.","authors":"Allison L Hunt, Waleed Barakat, Sasha C Makohon-Moore, Brian L Hood, Kelly A Conrads, Katlin N Wilson, Tamara Abulez, Jonathan Ogata, Kenneth J Pienta, Tamara L Lotan, Haresh Mani, Donald L Trump, Nicholas W Bateman, Thomas P Conrads","doi":"10.1186/s12014-025-09534-8","DOIUrl":"https://doi.org/10.1186/s12014-025-09534-8","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer is one of the most frequently diagnosed cancers in men. Prostate tumor staging and disease aggressiveness are evaluated based on the Gleason scoring system, which is further used to direct clinical intervention. The Gleason scoring system provides an estimate of tumor aggressiveness through quantitation of the serum level of prostate specific antigen (PSA) and histologic assessment of Grade Group, determined by the Gleason Grade of the tumor specimen.</p><p><strong>Methods: </strong>To improve our understanding of the proteomic characteristics differentiating low- versus high-grade prostate cancer tumors, we performed a deep proteomic characterization of laser microdissected epithelial and stromal subpopulations from surgically resected tissue specimens from patients with Gleason 6 (n = 23 specimens from n = 15 patients) and Gleason 9 (n = 15 specimens from n = 15 patients) prostate cancer via quantitative high-resolution liquid chromatography-tandem mass spectrometry analysis.</p><p><strong>Results: </strong>In total, 789 and 295 grade-specific significantly altered proteins were quantified in the tumor epithelium and tumor-involved stroma, respectively. Benign epithelial and stromal populations were not inherently different between Gleason 6 versus Gleason 9 specimens. Notably, 598 proteins were exclusively significantly altered between Gleason 9 (but not Gleason 6) tumor-involved stroma and benign stroma, including several proteins involved in cholesterol biosynthesis and nucleotide metabolism.</p><p><strong>Conclusions: </strong>Proteomic alterations between Gleason 6 versus Gleason 9 were exclusive to the disease microenvironment, observed in both the tumor epithelium and tumor-involved stroma. Further, the molecular alterations measured in the tumor-involved stroma from Gleason 9 cases relative to the benign stroma have unique significance in disease aggressiveness, development, and/or progression. Our data provide supportive evidence of a need for further investigations into targeting stromal reservoirs of cholesterol and/or deoxynucleoside triphosphates in PCa tumors and further highlight the necessity for independent examination of the TME epithelial and stromal compartments.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"22 1","pages":"14"},"PeriodicalIF":2.8,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990651","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":"Circulatory prostate cancer proteome landscapes and prognostic biomarkers in metastatic castrate resistant prostate cancer.","authors":"Hyejung Lee, Jincheng Shen, Muhammad Zaki Fadlullah, Anna Neibling, Claire Hanson, Enos Ampaw, Tengda Lin, Matt Larsen, Jennifer Lloyd, Benjamin L Maughan, Umang Swami, Sumati Gupta, Jonathan Tward, Skyler B Johnson, Brock O'Neil, Bogdana Schmidt, Christopher B Dechet, Benjamin Haaland, Liang Wang, Aik-Choon Tan, Manish Kohli","doi":"10.1186/s12014-025-09536-6","DOIUrl":"10.1186/s12014-025-09536-6","url":null,"abstract":"<p><strong>Background: </strong>Plasma-based high-plex proteomic profiling were performed in prostate cancer (PC) patients using the Olink® Explore Proximity Extension Assay to identify plasma proteins associated in different PC states and to explore potential prognostic biomarkers. The progressive PC states include local, organ-confined PC (local PC), metastatic hormone-sensitive PC (mHSPC) and metastatic castrate-resistant PC (mCRPC).</p><p><strong>Methods: </strong>Plasma samples were uniformly processed from 84 PC patients (10 patients with local PC; 29 patients with mHSPC; 45 patients with mCRPC). A proteome-wide association study was performed to identify proteins differentially overexpressed in progressive cancer states. Specifically, a sequential screening approach was employed where proteins overexpressed from one disease state were assessed for overexpression in the progressive disease state. Linear regression, analysis of variance, and t-tests were used for this approach. Differentially expressed proteins (DEPs) in mCRPC were then used to construct a prognostic model for overall survival (OS) in mCRPC patients using the Cox Proportional Hazard Model. The predictive performance of this model was assessed using time-dependent area under the receiver operating characteristic curves (tAUC) in an independent sample of mCRPC patients. The tAUC of the prognostic model was then compared to that of a model excluding DEPs to evaluate the added value of circulatory proteins in predicting survival.</p><p><strong>Results: </strong>Of 736 tumor-associated proteins, 26 were differentially expressed across local PC, mHSPC, and mCRPC states. Among these, 20 were overexpressed in metastatic states compared to local, and in mCRPC compared to mHSPC states. Of these 20 proteins, Ribonucleoside-diphosphate reductase subunit M2 (RRM2) was identified as a prognostic biomarker for OS in mCRPC, with a hazard ratio of 2.30 (95% confidence interval (CI) 1.17-4.51) per normalized expression unit increase. The tAUC of the model including previously identified clinical prognostic factors was 0.62 (95% CI 0.29-0.91), whereas the model that includes RRM2 with clinical prognostic factors was 0.87 (95% CI 0.51-0.98).</p><p><strong>Conclusions: </strong>Plasma proteome profiling can identify novel circulatory DEPs associated with mCRPC state survivals. Overexpression of RRM2 is linked to poor mCRPC survival and its inclusion alongside conventional prognostic factors enhances the predictive performance of the prognostic model.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"22 1","pages":"13"},"PeriodicalIF":3.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977247","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":"Proteomic profiles screening identified novel exosomal protein biomarkers for diagnosis of lung cancer.","authors":"Weiyan Feng, Ying Lin, Ling Zhang, Weiming Hu","doi":"10.1186/s12014-025-09535-7","DOIUrl":"https://doi.org/10.1186/s12014-025-09535-7","url":null,"abstract":"<p><strong>Background: </strong>Exosomes play important role in biological functions, including both normal and disease process. Multiple cell types can secret exosomes, which act as message carriers. Increased evidences reveal that exosomes are promising diagnosis biomarkers in malignant tumors.</p><p><strong>Methods: </strong>In this study, we enrolled 78 participants, including 20 lung adenocarcinoma (LUAD), 18 lung squamous carcinoma (LUSC), 20 lung benign diseases (LUBN) and 20 healthy controls (NL) and we performed parallel reaction-monitoring (PRM)-mass spectrometry to screening the proteomic variation by label free analysis in exosomes from all groups, which has been widely used to quantify and detect target proteins.</p><p><strong>Results: </strong>Total 14 protein were identified as candidate biomarkers, complement components C9, apolipoprotein B (APOB), filamin A (FLNA), guanine nucleotide binding protein G subunit 2 (GNB2), fermitin family homolog 3 (FERMT3) showed significantly differentiation in total lung cancer (LUAD and LUSC together), we then obtained combination analysis of 5 proteins and the area under the curve (AUC), sensitivity (SN) and specificity (SP) were 63.0%, 65.0%, and 75.0%, respectively, in comparison to NL group. And the LUAD combination panel, peroxiredoxin 6 (PRDX6), integrin alpha-IIb (ITGA2B) and hemoglobin subunit delta (HBD) revealed AUC was 95.0%, SN was 90.0% and SP was 95.0% in comparison to NL controls. In LUSC analysis, combination analysis of fibronectin 1 (FN1), pregnancy zone protein (PZP) and complement C1q tumor necrosis factor related protein 3 (C1QTNF3) showed that AUC was 88.1%, SN was 75.0%, SP was 100% in paralleled with NL group. Finally C9, FLNA, PZP were overexpressed in lung cancer H1299 and A549 cell lines and the results indicated that C9 acted as oncogenic role by increasing proliferation, migration and invasion of lung cancer cells, while FLNA and PZP played tumor-suppression by inhibition biological functions of lung cancer cells.</p><p><strong>Conclusion: </strong>Taken together, our study revealed multiple exosomal proteins which could be applied as candidate biomarkers in diagnosis of lung cancer.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"22 1","pages":"12"},"PeriodicalIF":2.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987600","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":"Plasma proteomics in pediatric patients with sepsis- hopes and challenges.","authors":"Shiyuan Fan, Saizhen Zeng","doi":"10.1186/s12014-025-09533-9","DOIUrl":"10.1186/s12014-025-09533-9","url":null,"abstract":"<p><p>One of the main causes of morbidity and death in pediatric patients is sepsis. Of the 48.9 million cases of sepsis reported globally, 41.5% involve children under the age of five, with 2.9 million deaths associated with the disease. Clinicians must identify and treat patients at risk of sepsis or septic shock before late-stage organ dysfunction occurs since diagnosing sepsis in young patients is more difficult than in adult patients. As of right now, omics technologies that possess adequate diagnostic sensitivity and specificity can assist in locating biomarkers that indicate how the disease will progress clinically and how the patient will react to treatment. By identifying patients who are at a higher risk of dying or experiencing persistent organ dysfunction, risk stratification based on biomarkers generated from proteomics can enhance prognosis. A potentially helpful method for determining the proteins that serve as biomarkers for sepsis and formulating theories on the pathophysiological mechanisms behind complex sepsis symptoms is plasma proteomics.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"22 1","pages":"10"},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647398","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":"Spatial top-down proteomics for the functional characterization of human kidney.","authors":"Kevin J Zemaitis, James M Fulcher, Rashmi Kumar, David J Degnan, Logan A Lewis, Yen-Chen Liao, Marija Veličković, Sarah M Williams, Ronald J Moore, Lisa M Bramer, Dušan Veličković, Ying Zhu, Mowei Zhou, Ljiljana Paša-Tolić","doi":"10.1186/s12014-025-09531-x","DOIUrl":"10.1186/s12014-025-09531-x","url":null,"abstract":"<p><strong>Background: </strong>The Human Proteome Project has credibly detected nearly 93% of the roughly 20,000 proteins which are predicted by the human genome. However, the proteome is enigmatic, where alterations in amino acid sequences from polymorphisms and alternative splicing, errors in translation, and post-translational modifications result in a proteome depth estimated at several million unique proteoforms. Recently mass spectrometry has been demonstrated in several landmark efforts mapping the human proteoform landscape in bulk analyses. Herein, we developed an integrated workflow for characterizing proteoforms from human tissue in a spatially resolved manner by coupling laser capture microdissection, nanoliter-scale sample preparation, and mass spectrometry imaging.</p><p><strong>Results: </strong>Using healthy human kidney sections as the case study, we focused our analyses on the major functional tissue units including glomeruli, tubules, and medullary rays. After laser capture microdissection, these isolated functional tissue units were processed with microPOTS (microdroplet processing in one-pot for trace samples) for sensitive top-down proteomics measurement. This provided a quantitative database of 616 proteoforms that was further leveraged as a library for mass spectrometry imaging with near-cellular spatial resolution over the entire section. Notably, several mitochondrial proteoforms were found to be differentially abundant between glomeruli and convoluted tubules, and further spatial contextualization was provided by mass spectrometry imaging confirming unique differences identified by microPOTS, and further expanding the field-of-view for unique distributions such as enhanced abundance of a truncated form (1-74) of ubiquitin within cortical regions.</p><p><strong>Conclusions: </strong>We developed an integrated workflow to directly identify proteoforms and reveal their spatial distributions. Of the 20 differentially abundant proteoforms identified as discriminate between tubules and glomeruli by microPOTS, the vast majority of tubular proteoforms were of mitochondrial origin (8 of 10) while discriminate proteoforms in glomeruli were primarily hemoglobin subunits (9 of 10). These trends were also identified within ion images demonstrating spatially resolved characterization of proteoforms that has the potential to reshape discovery-based proteomics because the proteoforms are the ultimate effector of cellular functions. Applications of this technology have the potential to unravel etiology and pathophysiology of disease states, informing on biologically active proteoforms, which remodel the proteomic landscape in chronic and acute disorders.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"22 1","pages":"9"},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566266","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":"Admission glucose, HbA1c levels and inflammatory cytokines in patients with acute ST-elevation myocardial infarction.","authors":"Meisinger Christa, Freuer Dennis, Raake Philip, Linseisen Jakob, Schmitz Timo","doi":"10.1186/s12014-025-09530-y","DOIUrl":"10.1186/s12014-025-09530-y","url":null,"abstract":"<p><strong>Background: </strong>To investigate the association between admission glucose and HbA1c values and inflammatory plasma proteins in hospitalized patients with acute ST-elevation myocardial infarction (STEMI).</p><p><strong>Methods: </strong>This analysis was based on 345 STEMI patients recorded by the population-based Myocardial Infarction Registry Augsburg between 2009 and 2013. Using the OLINK inflammatory panel, a total of 92 protein biomarkers were measured in arterial blood samples, which were obtained within the scope of cardiac catheterization immediately after admission. The associations between admission glucose and HbA1c levels and the 92 protein markers were investigated using multivariable linear regression models.</p><p><strong>Results: </strong>Admission glucose showed significantly positive associations with the inflammatory markers IL-10, IL-8, IL-6, FGF-21, IL-7, ST1A1, MCP-1, 4E-BP1, SIRT2, STAMBP and IL-18R1 after Bonferroni adjustment. HbA1c values were only significantly associated with IL-18R1. In stratified analyses, admission glucose was not significantly associated with any plasma protein in the diabetes subgroup, while there were several protein markers that showed significantly positive associations with admission glucose in STEMI patients without known diabetes, namely IL-10, CCL20, IL-8, MCP-1 and IL-6.</p><p><strong>Conclusions: </strong>Admission glucose in patients hospitalized due to an acute STEMI seems to be related to an inflammatory and immune-related response, expressed by an increase in inflammation-related plasma proteins in particular in non-diabetic patients with stress hyperglycemia. The present results may open new avenues for the development of biomarkers suitable as potential diagnostic or prognostic clinical markers.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"22 1","pages":"8"},"PeriodicalIF":2.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440173","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":"Identification of novel proteomic biomarkers for hypertension: a targeted approach for precision medicine.","authors":"Rana S Aldisi, Alsamman M Alsamman, Peter Krawitz, Carlo Maj, Hatem Zayed","doi":"10.1186/s12014-024-09519-z","DOIUrl":"10.1186/s12014-024-09519-z","url":null,"abstract":"<p><strong>Background: </strong>Hypertension is a critical public health issue worldwide. The identification of specific proteomic biomarkers in the Qatari population aims to advance personalized treatment strategies.</p><p><strong>Methods: </strong>We conducted proteomic profiling on 778 Qatari individuals using an aptamer-based SOMAscan platform to analyze 1,305 biomarkers. Statistical analysis involved two-way ANOVA and association analyses with FDR correction, alongside pathway and gene-set enrichment analyses using Reactome and DisGeNET databases.</p><p><strong>Results: </strong>The study identified 26 significant protein biomarkers associated with hypertension. Notably, QORL1 and BMP1 were identified as novel protein biomarkers. Enrichment analysis linked these biomarkers to critical pathways involved in vascular biology, immune system responses, and pathologies like arteriosclerosis and coronary artery disease. Correlation analyses highlighted robust interactions, particularly between QORL1 and various Apolipoprotein E isoforms, suggesting these biomarkers play pivotal roles in the molecular mechanisms underlying hypertension.</p><p><strong>Conclusions: </strong>This research enhances our understanding of the molecular basis of hypertension in the Qatari population and supports the development of precision medicine approaches for treatment.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"22 1","pages":"7"},"PeriodicalIF":2.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406104","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":"Integrated proteomics and N-glycoproteomic characterization of glioblastoma multiform revealed N-glycosylation heterogeneities as well as alterations in sialyation and fucosylation.","authors":"Mingjun Hu, Kaiyue Xu, Ge Yang, Bo Yan, Qianqian Yang, Liang Wang, Shisheng Sun, Huijuan Wang","doi":"10.1186/s12014-025-09525-9","DOIUrl":"10.1186/s12014-025-09525-9","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. Notwithstanding tremendous efforts having been put in multi-omics research to profile the dysregulated molecular mechanisms and cellular pathways, there is still a lack of understanding about the glycoproteomic of GBM. Glycosylation as one of the most important post-translational modifications is crucial in regulating cell proliferation and relevant oncogenic pathways.</p><p><strong>Results: </strong>In the study, we systematically profiled N-glycoproteomics of para-cancerous and cancerous tissues from GBM patients to reveal the site-specific N-glycosylation pattern defined by intact glycopeptides. We identified and quantified 1863 distinct intact glycopeptides (IGPs) with 161 N-linked glycan compositions and 326 glycosites. There were 396 IGPs from 43 glycoproteins differed between adjacent tissues and GBM. Then, proteomic and glycoproteomic data were combined, and the normalized glycosylation alteration was calculated to determine whether the difference was attributed to the global protein levels or glycosylation. The altered glycosylation triggered by site-specific N-glycans and glycoprotein abundance, as well as glycosite heterogeneity, were demonstrated. Ultimately, an examination of the overall glycosylation levels revealed a positive contribution of sialylated or/and fucosylated glycans.</p><p><strong>Conclusions: </strong>Overall, the dataset highlighted molecular complexity and distinct profiling at translational and post-translational levels, providing valuable information for novel therapeutic approaches and specific detection strategies.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"22 1","pages":"6"},"PeriodicalIF":2.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373997","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":"ARTN and CCL23 predicted chemosensitivity in acute myeloid leukemia: an Olink^® proteomics approach.","authors":"Ting-Shuan Wu, Tzu-Hung Hsiao, Chung-Hsing Chen, Hsin-Ni Li, Miao-Neng Hung, Pei-Pei Jhan, Jia-Rung Tsai, Chieh-Lin Jerry Teng","doi":"10.1186/s12014-025-09527-7","DOIUrl":"10.1186/s12014-025-09527-7","url":null,"abstract":"<p><strong>Background: </strong>The standard \"7 + 3\" induction results in 30% of de novo acute myeloid leukemia (AML) patients not achieving complete remission (CR). We aimed to utilize the Olink^® platform to compare the bone marrow plasma proteomic profiles of newly diagnosed de novo AML patients who did and did not achieve CR following \"7 + 3\" induction treatment.</p><p><strong>Methods: </strong>This prospective study included 43 untreated AML patients, stratified into CR (n = 29) and non-CR (n = 14) groups based on their response to \"7 + 3\" induction therapy. We employed the Olink^® Explore-384 Inflammation platform for proteomic analysis to investigate differences in bone marrow plasma protein levels between the CR and non-CR groups.</p><p><strong>Results: </strong>Proteomic analysis demonstrated that the CR group exhibited significantly higher bone marrow plasma levels of ARTN and CCL23 than did the non-CR group. Immunohistochemical staining confirmed a higher proportion of tissue samples with intense staining for ARTN (25.40% vs. 7.05%, p = 0.013) and CCL23 (24.14% vs. 14.29%, p = 0.039) in the CR group. These findings were corroborated by bulk-RNA-seq, which indicated significantly elevated mRNA expression levels of ARTN (1.93 vs. -0.09; p = 0.003) and CCL23 (1.50 vs. 0.12; p = 0.021) in the CR group. The Human Protein Atlas provided external support for our findings.</p><p><strong>Conclusions: </strong>The results suggest that ARTN and CCL23 may serve as biomarkers for predicting responsiveness to the \"7 + 3\" induction in untreated AML. Using an enzyme-linked immunosorbent assay to identify the roles of ARTN and CCL23 in predicting AML chemosensitivity may enhance clinical applicability in the future.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"22 1","pages":"3"},"PeriodicalIF":2.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001371","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":"Medwakh smoking induces alterations in salivary proteins and cytokine expression: a clinical exploratory proteomics investigation.","authors":"K G Aghila Rani, Nelson C Soares, Betul Rahman, Alexander D Giddey, Hamza M Al-Hroub, Mohammad H Semreen, Sausan Al Kawas","doi":"10.1186/s12014-024-09520-6","DOIUrl":"10.1186/s12014-024-09520-6","url":null,"abstract":"<p><strong>Background: </strong>Medwakh smoking has radically expanded among youth in the Middle East and around the world. The rising popularity of medwakh/dokha usage is linked to the onset of several chronic illnesses including cardiovascular diseases and cancers. Medwakh smoking is reported to increase the risk of inflammation in the lower respiratory tract owing to oxidative burden. To date, there are no reported studies investigating the impact of medwakh smoking on salivary protein profile. The current study aims to elucidate alterations in the salivary proteome profile of medwakh smokers.</p><p><strong>Methods: </strong>Saliva samples collected from 33 medwakh smokers and 30 non-smokers were subjected to proteomic analysis using UHPLC-ESI-QTOF-MS. Saliva samples were further subjected to validatory experiments involving analysis of inflammatory cytokine profile using LEGENDplex™ Human Essential Immune Response Panel.</p><p><strong>Results: </strong>Statistical analysis revealed alterations in the abundance of 74 key proteins including immune mediators and inflammatory markers in medwakh smokers (Accession: PXD045901). Proteins involved in building oxidative stress, alterations in cell anchorage, and cell metabolic processes were enhanced in medwakh smokers. Salivary immune response evaluation further validated the proteome findings, revealing significantly higher levels of IL-1β, IL-12p70, IL-23, IFN-γ (Th1 cytokines), IL-6 (Th2 cytokine), and MCP-1 (chemokine) in medwakh smokers. In addition, a substantial increase in abundance of involucrin suggesting a plausible stratified squamous cell differentiation and increased cell lysis in the oral cavity of medwakh smokers akin to chronic obstructive pulmonary diseases (COPD). The protein-metabolite joint pathway analysis further showed significantly enriched differentially expressed proteins and metabolites of glycolysis/gluconeogenesis, pentose phosphate, fructose and mannose, nicotinate and nicotinamide, and glutathione metabolism pathways among medwakh smokers.</p><p><strong>Conclusions: </strong>The findings of the study provide valuable insights on potential perturbations in various key immune molecules, cytokines, and signaling pathways among medwakh smokers. Medwakh smokers displayed elevated inflammation, increased oxidative stress and defective antioxidant responses, dysregulated energy metabolism, and alterations in proteins related to cell adhesion, migration, differentiation, and proliferation. The findings of study underscore the urgent need for comprehensive public health interventions among youth by raising awareness, implementing effective smoking cessation programs, and promoting healthy lifestyle to safeguard the well-being of individuals and communities worldwide.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"22 1","pages":"2"},"PeriodicalIF":2.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001374","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}