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。

IF 3.3 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS
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}
引用次数: 0

摘要

背景:前列腺癌是男性中最常见的癌症之一。根据Gleason评分系统评估前列腺肿瘤分期和疾病侵袭性,进一步用于指导临床干预。Gleason评分系统通过定量测定血清前列腺特异性抗原(PSA)水平和分级组的组织学评估(由肿瘤标本的Gleason分级决定)来估计肿瘤的侵袭性。方法:为了提高我们对区分低级别和高级别前列腺癌肿瘤的蛋白质组学特征的理解,我们通过定量高分辨率液相色谱-串联质谱分析,对Gleason 6 (n = 15例患者的23例标本)和Gleason 9 (n = 15例患者的15例标本)前列腺癌患者手术切除组织标本的激光微解剖上皮和间质亚群进行了深入的蛋白质组学表征。结果:在肿瘤上皮和肿瘤累及间质中,分别定量检测到789和295种分级特异性显著改变的蛋白。Gleason 6和Gleason 9标本间的良性上皮和间质群体没有内在差异。值得注意的是,598个蛋白在Gleason 9(而不是Gleason 6)肿瘤累及的基质和良性基质之间发生了显著的改变,包括一些参与胆固醇生物合成和核苷酸代谢的蛋白。结论:Gleason 6和Gleason 9之间的蛋白质组学改变是疾病微环境所特有的,在肿瘤上皮和肿瘤累及的基质中都观察到。此外,相对于良性间质,Gleason 9病例中肿瘤累及间质的分子改变在疾病侵袭性、发展和/或进展中具有独特的意义。我们的数据为进一步研究前列腺癌肿瘤中靶向胆固醇和/或三磷酸脱氧核苷的基质库提供了支持性证据,并进一步强调了对TME上皮和基质室进行独立检查的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Clinical proteomics
Clinical proteomics BIOCHEMICAL RESEARCH METHODS-
CiteScore
5.80
自引率
2.60%
发文量
37
审稿时长
17 weeks
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信