Minsun Jung, Bohyun Kim, Jae Seok Lee, Jun Yong Kim, Dohyun Han, Kwangsoo Kim, Sunah Yang, Eun Na Kim, Hyeyooon Kim, Ilias P Nikas, Sohyeon Yang, Kyung Chul Moon, Hyebin Lee, Han Suk Ryu
{"title":"在评估低级别乳头状尿路上皮肿瘤时,KRT18 是尿路乳头状瘤的新型生物标记物:双中心分析","authors":"Minsun Jung, Bohyun Kim, Jae Seok Lee, Jun Yong Kim, Dohyun Han, Kwangsoo Kim, Sunah Yang, Eun Na Kim, Hyeyooon Kim, Ilias P Nikas, Sohyeon Yang, Kyung Chul Moon, Hyebin Lee, Han Suk Ryu","doi":"10.1159/000540926","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Although urothelial papilloma (UP) is an indolent papillary neoplasm that can mimic the morphology of low-grade papillary urothelial carcinoma (PUC), there is no immunomarker to differentiate reliably these two entities. In addition, the molecular characteristics of UP are not fully understood.</p><p><strong>Methods: </strong>We conducted an in-depth proteomic analysis of papillary urothelial lesions (n = 31), including UP and PUC along with normal urothelium. Protein markers distinguishing UP and PUC were selected with machine learning analysis, followed by internal and external validation using immunohistochemistry.</p><p><strong>Results: </strong>In the proteomic analysis, UP and PUC showed overlapping proteomic profiles. We identified EHD4 and KRT18 as candidate diagnostic biomarkers of UP. Through immunohistochemical validation in two independent cohorts (n = 120), KRT18 was suggested as a novel UP diagnostic marker, able to differentiate UP from low-grade PUC. We also found that 3.5% of patients with UP developed urothelial carcinoma in subsequent resections, supporting the malignant potential of UP. KRT18 downregulation was significantly associated with UPs subsequently progressing to urothelial carcinoma, following their initial diagnosis.</p><p><strong>Conclusion: </strong>This is the first study that successfully revealed UPs comprehensive proteomic landscape, while it also identified KRT18 as a potential diagnostic biomarker of UP.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"KRT18 as a Novel Biomarker of Urothelial Papilloma while Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis.\",\"authors\":\"Minsun Jung, Bohyun Kim, Jae Seok Lee, Jun Yong Kim, Dohyun Han, Kwangsoo Kim, Sunah Yang, Eun Na Kim, Hyeyooon Kim, Ilias P Nikas, Sohyeon Yang, Kyung Chul Moon, Hyebin Lee, Han Suk Ryu\",\"doi\":\"10.1159/000540926\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Although urothelial papilloma (UP) is an indolent papillary neoplasm that can mimic the morphology of low-grade papillary urothelial carcinoma (PUC), there is no immunomarker to differentiate reliably these two entities. In addition, the molecular characteristics of UP are not fully understood.</p><p><strong>Methods: </strong>We conducted an in-depth proteomic analysis of papillary urothelial lesions (n = 31), including UP and PUC along with normal urothelium. Protein markers distinguishing UP and PUC were selected with machine learning analysis, followed by internal and external validation using immunohistochemistry.</p><p><strong>Results: </strong>In the proteomic analysis, UP and PUC showed overlapping proteomic profiles. We identified EHD4 and KRT18 as candidate diagnostic biomarkers of UP. Through immunohistochemical validation in two independent cohorts (n = 120), KRT18 was suggested as a novel UP diagnostic marker, able to differentiate UP from low-grade PUC. We also found that 3.5% of patients with UP developed urothelial carcinoma in subsequent resections, supporting the malignant potential of UP. KRT18 downregulation was significantly associated with UPs subsequently progressing to urothelial carcinoma, following their initial diagnosis.</p><p><strong>Conclusion: </strong>This is the first study that successfully revealed UPs comprehensive proteomic landscape, while it also identified KRT18 as a potential diagnostic biomarker of UP.</p>\",\"PeriodicalId\":19805,\"journal\":{\"name\":\"Pathobiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-08-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pathobiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000540926\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pathobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000540926","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
导言:尽管尿路乳头状瘤(UP)是一种不活跃的乳头状肿瘤,其形态可与低级别乳头状尿路上皮癌(PUC)相似,但目前尚无可靠的免疫标志物来区分这两种实体。此外,UP 的分子特征也不完全清楚:我们对乳头状尿路上皮病变(31 人)进行了深入的蛋白质组学分析,包括 UP 和 PUC 以及正常尿路上皮。通过机器学习分析筛选出区分UP和PUC的蛋白质标记物,然后使用免疫组化进行内部和外部验证:结果:在蛋白质组分析中,UP 和 PUC 显示出重叠的蛋白质组特征。我们发现EHD4和KRT18是UP的候选诊断生物标记物。通过在两个独立队列(n=120)中进行免疫组化验证,KRT18被认为是新的UP诊断标志物,能够区分UP和低级别PUC。我们还发现,3.5%的UP患者在随后的切除手术中发展为尿路上皮癌,这支持了UP的恶性潜能。KRT18下调与UPs在最初诊断后发展为尿路上皮癌明显相关:结论:这是第一项成功揭示UP的全面蛋白质组图谱的研究,同时还发现KRT18是UP的潜在诊断生物标志物。
KRT18 as a Novel Biomarker of Urothelial Papilloma while Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis.
Introduction: Although urothelial papilloma (UP) is an indolent papillary neoplasm that can mimic the morphology of low-grade papillary urothelial carcinoma (PUC), there is no immunomarker to differentiate reliably these two entities. In addition, the molecular characteristics of UP are not fully understood.
Methods: We conducted an in-depth proteomic analysis of papillary urothelial lesions (n = 31), including UP and PUC along with normal urothelium. Protein markers distinguishing UP and PUC were selected with machine learning analysis, followed by internal and external validation using immunohistochemistry.
Results: In the proteomic analysis, UP and PUC showed overlapping proteomic profiles. We identified EHD4 and KRT18 as candidate diagnostic biomarkers of UP. Through immunohistochemical validation in two independent cohorts (n = 120), KRT18 was suggested as a novel UP diagnostic marker, able to differentiate UP from low-grade PUC. We also found that 3.5% of patients with UP developed urothelial carcinoma in subsequent resections, supporting the malignant potential of UP. KRT18 downregulation was significantly associated with UPs subsequently progressing to urothelial carcinoma, following their initial diagnosis.
Conclusion: This is the first study that successfully revealed UPs comprehensive proteomic landscape, while it also identified KRT18 as a potential diagnostic biomarker of UP.
期刊介绍:
''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.