Clinical proteomics最新文献

{"title":"Lessons learned: establishing a CLIA-equivalent laboratory for targeted mass spectrometry assays – navigating the transition from research to clinical practice","authors":"Chia-Li Han, Chi-Ting Lai, Aaron James Reyes, Hao-Chin Yang, Jin-Ying Lu, Shyang-Rong Shih, Kuen-Yuan Chen, Andrew N. Hoofnagle, Sung-Liang Yu, William Bocik, Tara Hiltke, Huan-Chi Chiu, Ching-Yi Wan, Henry Rodriguez, Victoria Zhang, Yu-Ju Chen","doi":"10.1186/s12014-024-09455-y","DOIUrl":"https://doi.org/10.1186/s12014-024-09455-y","url":null,"abstract":"Mass spectrometry (MS) assays offer exceptional capabilities in high multiplexity, specificity, and throughput. As proteomics technologies continue advancements to identify new disease biomarkers, transition of these innovations from research settings to clinical applications becomes imperative. To meet the rigorous regulatory standards of clinical laboratories, development of a clinical protein MS assay necessitates adherence to stringent criteria. To illustrate the process, this project focused on using thyroglobulin (Tg) as a biomarker and an immuno-multiple reaction monitoring (iMRM) MS-based assay as a model for establishing a Clinical Laboratory Improvement Amendments (CLIA) compliant laboratory within the Centers of Genomic and Precision Medicine, National Taiwan University. The chosen example also illustrates the clinical utility of MS assays to complement conventional immunoassay-based methods, particularly in cases where the presence of autoantibodies in 10–30% of patients hinders accuracy. The laboratory design entails a comprehensive coordination in spatial layout, workflow organization, equipment selection, ventilation systems, plumbing, electrical infrastructure, documentation procedures, and communication protocols. Practical aspects of the transformation process, including preparing laboratory facilities, testing environments, instrument validation, assay development and validation, quality management, sample testing, and personnel competency, are discussed. Finally, concordant results in proficiency testing demonstrate the harmonization with the University of Washington Medical Center and the quality assurance of the CLIA-equivalent Tg-iMRM MS assay established in Taiwan. The realization of this model protein MS assay in Taiwan highlights the feasibility of international joint development and provides a detailed reference map to expedite the implementation of more MS-based protein assays in clinical laboratories for patient care.","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"11 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139925524","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":"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 Fraser, Shawn Shun-Cheng Li","doi":"10.1186/s12014-024-09457-w","DOIUrl":"https://doi.org/10.1186/s12014-024-09457-w","url":null,"abstract":"SARS-CoV-2 infection triggers extensive host immune reactions, leading to severe diseases in certain individuals. However, the molecular basis underlying the excessive yet non-productive immune responses in severe COVID-19 remains incompletely understood. In this study, we conducted a comprehensive analysis of the peripheral blood mononuclear cell (PBMC) proteome and phosphoproteome in sepsis patients positive or negative for SARS-CoV-2 infection, as well as healthy subjects, using quantitative mass spectrometry. Our findings demonstrate dynamic changes in the COVID-19 PBMC proteome and phosphoproteome during disease progression, with distinctive protein or phosphoprotein signatures capable of distinguishing longitudinal disease states. Furthermore, SARS-CoV-2 infection induces a global reprogramming of the kinome and phosphoproteome, resulting in defective adaptive immune response mediated by the B and T lymphocytes, compromised innate immune responses involving the SIGLEC and SLAM family of immunoreceptors, and excessive cytokine-JAK-STAT signaling. In addition to uncovering host proteome and phosphoproteome aberrations caused by SARS-CoV-2, our work recapitulates several reported therapeutic targets for COVID-19 and identified numerous new candidates, including the kinases PKG1, CK2, ROCK1/2, GRK2, SYK, JAK2/3, TYK2, DNA-PK, PKCδ, and the cytokine IL-12.","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"72 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139925591","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":"Comparison of early changes in tear film protein profiles after small incision lenticule extraction (SMILE) and femtosecond LASIK (FS-LASIK) surgery","authors":"Petri Mäkinen, Janika Nättinen, Ulla Aapola, Juhani Pietilä, Hannu Uusitalo","doi":"10.1186/s12014-024-09460-1","DOIUrl":"https://doi.org/10.1186/s12014-024-09460-1","url":null,"abstract":"Small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (LASIK) are widely used surgical methods to correct myopia with comparable efficacy, predictability, and safety. We examined and compared the early changes of tear protein profiles after SMILE and FS-LASIK surgery in order to find possible differences in the initial corneal healing process. SMILE operations for 26 eyes were made with Visumax femtosecond laser. In FS-LASIK surgery for 30 eyes, the flaps were made with Ziemer FEMTO LDV Z6 femtosecond laser and stromal ablation with Wavelight EX500 excimer laser. Tear samples were collected preoperatively, and 1.5 h and 1 month postoperatively using glass microcapillary tubes. Tear protein identification and quantification were performed with sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS). Immediately (1.5 h) after we found differences in 89 proteins after SMILE and in 123 after FS-LASIK operation compared to preoperative protein levels. Of these differentially expressed proteins, 48 proteins were common for both surgery types. There were, however, quantitative differences between SMILE and FS-LASIK. Upregulated proteins were mostly connected to inflammatory response and migration of the cells connected to immune system. One month after the operation protein expressions levels were returned to baseline levels with both surgical methods. Our study showed that immediate changes in protein profiles after SMILE and FS-LASIK surgeries and differences between the methods are connected to inflammatory process, and the protein levels quickly return to the baseline within 1 month. The differences in protein profiles between the methods are probably associated with the different size of the epithelial wound induced.","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"50 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139767975","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":"Exploring the novel duo of Reticulocalbin, and Sideroflexin as future biomarker candidates for Exacerbated Chronic Obstructive Pulmonary Disease.","authors":"Sonu Das, Supriya Adiody, Jinsu Varghese, M Vanditha, Evelyn Maria, Mathew John","doi":"10.1186/s12014-024-09459-8","DOIUrl":"10.1186/s12014-024-09459-8","url":null,"abstract":"<p><strong>Background: </strong>COPD is a complex respiratory disorder with high morbidity and mortality rates. Even with the current conventional diagnostic methods, including circulating inflammatory biomarkers, underdiagnosis rates in COPD remain as high as 70%. Our study was a comparative cross-sectional study that aimed to address the diagnostic challenges by identifying future biomarker candidates in COPD variants.</p><p><strong>Methods: </strong>This study used a label-free plasma proteomics approach that combined mass spectrometric data with bioinformatics to shed light on the functional roles of differentially expressed proteins in the COPD lung microenvironment. The predictive capacity of the screened proteins was assessed using Receiver Operating Characteristic (ROC) curves, with Western blot analysis validating protein expression patterns in an independent cohort.</p><p><strong>Results: </strong>Our study identified three DEPs-reticulocalbin-1, sideroflexin-4, and liprinα-3 that consistently exhibited altered expression in COPD exacerbation. ROC analysis indicated strong predictive potential, with AUC values of 0.908, 0.715, and 0.856 for RCN1, SFXN4, and LIPα-3, respectively. Validation through Western blot analysis confirmed their expression patterns in an independent validation cohort.</p><p><strong>Conclusions: </strong>Our study discovered a novel duo of proteins reticulocalbin-1, and sideroflexin-4 that showed potential as valuable future biomarkers for the diagnosis and clinical management of COPD exacerbations.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"10"},"PeriodicalIF":3.8,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734677","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: Glial cell proteome using targeted quantitative methods for potential multi-diagnostic biomarkers.","authors":"Narae Kang, Hyun Jeong Oh, Ji Hye Hong, Hyo Eun Moon, Yona Kim, Hyeon-Jeong Lee, Hophil Min, Hyeonji Park, Sang Hun Lee, Sun Ha Paek, Jonghwa Jin","doi":"10.1186/s12014-024-09456-x","DOIUrl":"10.1186/s12014-024-09456-x","url":null,"abstract":"","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"9"},"PeriodicalIF":3.8,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10858455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139715892","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":"Absolute quantitation of human wild-type DNAI1 protein in lung tissue using a nanoLC-PRM-MS-based targeted proteomics approach coupled with immunoprecipitation.","authors":"Hui Wang, Xiaoyan Ni, Nicholas Clark, Kristen Randall, Lianne Boeglin, Sudha Chivukula, Caroline Woo, Frank DeRosa, Gang Sun","doi":"10.1186/s12014-024-09453-0","DOIUrl":"10.1186/s12014-024-09453-0","url":null,"abstract":"<p><strong>Background: </strong>Dynein axonemal intermediate chain 1 protein (DNAI1) plays an essential role in cilia structure and function, while its mutations lead to primary ciliary dyskinesia (PCD). Accurate quantitation of DNAI1 in lung tissue is crucial for comprehensive understanding of its involvement in PCD, as well as for developing the potential PCD therapies. However, the current protein quantitation method is not sensitive enough to detect the endogenous level of DNAI1 in complex biological matrix such as lung tissue.</p><p><strong>Methods: </strong>In this study, a quantitative method combining immunoprecipitation with nanoLC-MS/MS was developed to measure the expression level of human wild-type (WT) DNAI1 protein in lung tissue. To our understanding, it is the first immunoprecipitation (IP)-MS based method for absolute quantitation of DNAI1 protein in lung tissue. The DNAI1 quantitation was achieved through constructing a standard curve with recombinant human WT DNAI1 protein spiked into lung tissue matrix.</p><p><strong>Results: </strong>This method was qualified with high sensitivity and accuracy. The lower limit of quantitation of human DNAI1 was 4 pg/mg tissue. This assay was successfully applied to determine the endogenous level of WT DNAI1 in human lung tissue.</p><p><strong>Conclusions: </strong>The results clearly demonstrate that the developed assay can accurately quantitate low-abundance WT DNAI1 protein in human lung tissue with high sensitivity, indicating its high potential use in the drug development for DNAI1 mutation-caused PCD therapy.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"8"},"PeriodicalIF":3.8,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10840268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680807","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":"Recent developments in mass-spectrometry-based targeted proteomics of clinical cancer biomarkers.","authors":"Deborah Wenk, Charlotte Zuo, Thomas Kislinger, Lusia Sepiashvili","doi":"10.1186/s12014-024-09452-1","DOIUrl":"10.1186/s12014-024-09452-1","url":null,"abstract":"<p><p>Routine measurement of cancer biomarkers is performed for early detection, risk classification, and treatment monitoring, among other applications, and has substantially contributed to better clinical outcomes for patients. However, there remains an unmet need for clinically validated assays of cancer protein biomarkers. Protein tumor markers are of particular interest since proteins carry out the majority of biological processes and thus dynamically reflect changes in cancer pathophysiology. Mass spectrometry-based targeted proteomics is a powerful tool for absolute peptide and protein quantification in biological matrices with numerous advantages that make it attractive for clinical applications in oncology. The use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) based methodologies has allowed laboratories to overcome challenges associated with immunoassays that are more widely used for tumor marker measurements. Yet, clinical implementation of targeted proteomics methodologies has so far been limited to a few cancer markers. This is due to numerous challenges associated with paucity of robust validation studies of new biomarkers and the labor-intensive and operationally complex nature of LC-MS/MS workflows. The purpose of this review is to provide an overview of targeted proteomics applications in cancer, workflows used in targeted proteomics, and requirements for clinical validation and implementation of targeted proteomics assays. We will also discuss advantages and challenges of targeted MS-based proteomics assays for clinical cancer biomarker analysis and highlight some recent developments that will positively contribute to the implementation of this technique into clinical laboratories.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"6"},"PeriodicalIF":2.8,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10826105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575428","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":"Frozen tissue coring and layered histological analysis improves cell type-specific proteogenomic characterization of pancreatic adenocarcinoma","authors":"Sara R. Savage, Yuefan Wang, Lijun Chen, Scott Jewell, Chelsea Newton, Yongchao Dou, Qing Kay Li, Oliver F. Bathe, Ana I. Robles, Gilbert S. Omenn, Mathangi Thiagarajan, Hui Zhang, Galen Hostetter, Bing Zhang","doi":"10.1186/s12014-024-09450-3","DOIUrl":"https://doi.org/10.1186/s12014-024-09450-3","url":null,"abstract":"Omics characterization of pancreatic adenocarcinoma tissue is complicated by the highly heterogeneous and mixed populations of cells. We evaluate the feasibility and potential benefit of using a coring method to enrich specific regions from bulk tissue and then perform proteogenomic analyses. We used the Biopsy Trifecta Extraction (BioTExt) technique to isolate cores of epithelial-enriched and stroma-enriched tissue from pancreatic tumor and adjacent tissue blocks. Histology was assessed at multiple depths throughout each core. DNA sequencing, RNA sequencing, and proteomics were performed on the cored and bulk tissue samples. Supervised and unsupervised analyses were performed based on integrated molecular and histology data. Tissue cores had mixed cell composition at varying depths throughout. Average cell type percentages assessed by histology throughout the core were better associated with KRAS variant allele frequencies than standard histology assessment of the cut surface. Clustering based on serial histology data separated the cores into three groups with enrichment of neoplastic epithelium, stroma, and acinar cells, respectively. Using this classification, tumor overexpressed proteins identified in bulk tissue analysis were assigned into epithelial- or stroma-specific categories, which revealed novel epithelial-specific tumor overexpressed proteins. Our study demonstrates the feasibility of multi-omics data generation from tissue cores, the necessity of interval H&E stains in serial histology sections, and the utility of coring to improve analysis over bulk tissue data.","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"101 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584257","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":"An LC-MS-based designated comparison method with similar performance to the Lp(a) reference measurement procedure to guide molar Lp(a) standardization.","authors":"Nina M Diederiks, L Renee Ruhaak, Fred P H T M Romijn, Mervin M Pieterse, Nico P M Smit, Christa M Cobbaert","doi":"10.1186/s12014-023-09446-5","DOIUrl":"10.1186/s12014-023-09446-5","url":null,"abstract":"<p><strong>Background: </strong>The 2022 consensus statement of the European Atherosclerosis Society (EAS) on lipoprotein(a) (Lp(a)) recognizes the role of Lp(a) as a relevant genetically determined risk factor and recommends its measurement at least once in an individual's lifetime. It also strongly urges that Lp(a) test results are expressed as apolipoprotein (a) (apo(a)) amount of substance in molar units and no longer in confounded Lp(a) mass units (mg/dL or mg/L). Therefore, IVD manufacturers should transition to molar units. A prerequisite for this transition is the availability of an Lp(a) Reference Measurement Procedure (RMP) that allows unequivocal molecular detection and quantification of apo(a) in Lp(a). To that end an ISO 17511:2020 compliant LC-MS based and IFCC-endorsed RMP has been established that targets proteotypic peptides of apolipoprotein(a) (apo(a)) in Lp(a). The RMP is laborious and requires highly skilled operators. To guide IVD-manufacturers of immunoassay-based Lp(a) test kits in the transition from mass to molar units, a Designated Comparison Method (DCM) has been developed and evaluated.</p><p><strong>Methods: </strong>To assess whether the DCM provides equivalent results compared to the RMP, the procedural designs were compared and the analytical performance of DCM and RMP were first evaluated in a head-to-head comparison. Subsequently, apo(a) was quantified in 153 human clinical serum samples. Both DCM and RMP were calibrated using external native calibrators that produce results traceable to SRM2B. Measurement uncertainty (MU) was checked against predefined allowable MU.</p><p><strong>Results: </strong>The major difference in the design of the DCM for apo(a) is the use of only one enzymatic digestion step. The analytical performance of the DCM and RMP for apo(a) is highly similar. In a direct method comparison, equivalent results were obtained with a median regression slope 0.997 of and a median bias of - 0.2 nmol/L (- 0.2%); the intermediate imprecision of the test results was within total allowable error (TEa) (CVa of 10.2% at 90 nmol/L).</p><p><strong>Conclusions: </strong>The semi-automated, higher throughput, LC-MS-based method for Lp(a) meets the predefined analytical performance specifications and allowable MU and is hence applicable as a higher order Designated Comparison Method, which is ideally suited to guide IVD manufacturers in the transition from Lp(a) mass to molar units.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"5"},"PeriodicalIF":2.8,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10809433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139544871","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 three-dimensional intratumor proteomic heterogeneity in uterine serous carcinoma by multiregion microsampling.","authors":"Allison L Hunt, Nicholas W Bateman, Waleed Barakat, Sasha C Makohon-Moore, Tamara Abulez, Jordan A Driscoll, Joshua P Schaaf, Brian L Hood, Kelly A Conrads, Ming Zhou, Valerie Calvert, Mariaelena Pierobon, Jeremy Loffredo, Katlin N Wilson, Tracy J Litzi, Pang-Ning Teng, Julie Oliver, Dave Mitchell, Glenn Gist, Christine Rojas, Brian Blanton, Kathleen M Darcy, Uma N M Rao, Emanuel F Petricoin, Neil T Phippen, G Larry Maxwell, Thomas P Conrads","doi":"10.1186/s12014-024-09451-2","DOIUrl":"10.1186/s12014-024-09451-2","url":null,"abstract":"<p><strong>Background: </strong>Although uterine serous carcinoma (USC) represents a small proportion of all uterine cancer cases, patients with this aggressive subtype typically have high rates of chemotherapy resistance and disease recurrence that collectively result in a disproportionately high death rate. The goal of this study was to provide a deeper view of the tumor microenvironment of this poorly characterized uterine cancer variant through multi-region microsampling and quantitative proteomics.</p><p><strong>Methods: </strong>Tumor epithelium, tumor-involved stroma, and whole \"bulk\" tissue were harvested by laser microdissection (LMD) from spatially resolved levels from nine USC patient tumor specimens and underwent proteomic analysis by mass spectrometry and reverse phase protein arrays, as well as transcriptomic analysis by RNA-sequencing for one patient's tumor.</p><p><strong>Results: </strong>LMD enriched cell subpopulations demonstrated varying degrees of relatedness, indicating substantial intratumor heterogeneity emphasizing the necessity for enrichment of cellular subpopulations prior to molecular analysis. Known prognostic biomarkers were quantified with stable levels in both LMD enriched tumor and stroma, which were shown to be highly variable in bulk tissue. These USC data were further used in a comparative analysis with a data generated from another serous gynecologic malignancy, high grade serous ovarian carcinoma, and have been added to our publicly available data analysis tool, the Heterogeneity Analysis Portal ( https://lmdomics.org/ ).</p><p><strong>Conclusions: </strong>Here we identified extensive three-dimensional heterogeneity within the USC tumor microenvironment, with disease-relevant biomarkers present in both the tumor and the stroma. These data underscore the critical need for upfront enrichment of cellular subpopulations from tissue specimens for spatial proteogenomic analysis.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"4"},"PeriodicalIF":2.8,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10804562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520144","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}