KRT18 as a Novel Biomarker of Urothelial Papilloma while Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis

被引:2
作者
Jung, Minsun [1 ]
Kim, Bohyun [2 ]
Lee, Jae Seok [3 ]
Kim, Jun Yong [1 ]
Han, Dohyun [4 ,5 ]
Kim, Kwangsoo [4 ]
Yang, Sunah [4 ]
Kim, Eun Na [6 ]
Kim, Hyeyooon [7 ]
Nikas, Ilias P. [8 ]
Yang, Sohyeon [6 ,9 ]
Moon, Kyung Chul [6 ,9 ,10 ]
Lee, Hyebin [11 ]
Ryu, Han Suk [6 ,9 ,12 ]
机构
[1] Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea
[2] Konkuk Univ, Sch Med, Med Ctr, Dept Pathol, Seoul, South Korea
[3] Sungkyunkwan Univ, Sch Med, Samsung Changwon Hosp, Dept Pathol, Chang Won, South Korea
[4] Seoul Natl Univ Hosp, Transdisciplinary Dept Med & Adv Technol, Seoul, South Korea
[5] Seoul Natl Univ Hosp, Biomed Res Inst, Prote Core Facil, Seoul 03080, South Korea
[6] Seoul Natl Univ Hosp, Dept Pathol, Seoul 03080, South Korea
[7] Pacific Northwest Natl Lab, Biol Sci Div, Richland, WA USA
[8] Univ Cyprus, Med Sch, Nicosia, Cyprus
[9] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul, South Korea
[10] Seoul Natl Univ, Coll Med, Kidney Res Inst, Med Res Ctr, Seoul, South Korea
[11] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Dept Radiat Oncol, Seoul, South Korea
[12] Seoul Natl Univ, Canc Res Inst, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
Urothelial papilloma; Papillary urothelial carcinoma; Tandem mass spectrometry; Machine learning analysis; Biomarkers; BLADDER-CANCER; COMPUTATIONAL PLATFORM; CYTOKERATIN; 18; EXPRESSION; MUTATIONS;
D O I
10.1159/000540926
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:28 / 39
页数:12
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