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
{"title":"组织学分辨的蛋白质组学揭示了低级别和高级别前列腺癌不同的肿瘤和间质特征。","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":null,"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":3.3000,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009531/pdf/","citationCount":"0","resultStr":"{\"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\":null,\"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\":3.3000,\"publicationDate\":\"2025-04-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009531/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical proteomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12014-025-09534-8\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical proteomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12014-025-09534-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Histology-resolved proteomics reveals distinct tumor and stromal profiles in low- and high-grade prostate cancer.
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍:
Clinical Proteomics encompasses all aspects of translational proteomics. Special emphasis will be placed on the application of proteomic technology to all aspects of clinical research and molecular medicine. The journal is committed to rapid scientific review and timely publication of submitted manuscripts.