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上皮间质转化失调驱动侵袭性肉瘤样膀胱癌的进展。

Dysregulation of EMT Drives the Progression to Clinically Aggressive Sarcomatoid Bladder Cancer.

机构信息

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.

出版信息

Cell Rep. 2019 May 7;27(6):1781-1793.e4. doi: 10.1016/j.celrep.2019.04.048.

DOI:10.1016/j.celrep.2019.04.048
PMID:31067463
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6546434/
Abstract

Sarcomatoid urothelial bladder cancer (SARC) displays a high propensity for distant metastasis and is associated with short survival. We report a comprehensive genomic analysis of 28 cases of SARC and 84 cases of conventional urothelial carcinoma (UC), with the TCGA cohort of 408 muscle-invasive bladder cancers serving as the reference. SARCs show a distinct mutational landscape, with enrichment of TP53, RB1, and PIK3CA mutations. They are related to the basal molecular subtype of conventional UCs and could be divided into epithelial-basal and more clinically aggressive mesenchymal subsets on the basis of TP63 and its target gene expression levels. Other analyses reveal that SARCs are driven by downregulation of homotypic adherence genes and dysregulation of the EMT network, and nearly half exhibit a heavily infiltrated immune phenotype. Our observations have important implications for prognostication and the development of more effective therapies for this highly lethal variant of bladder cancer.

摘要

肉瘤样尿路上皮膀胱癌 (SARC) 具有较高的远处转移倾向，且与较短的生存期相关。我们报告了对 28 例 SARC 和 84 例传统尿路上皮癌 (UC) 的全面基因组分析，TCGA 队列的 408 例肌层浸润性膀胱癌作为参考。SARC 显示出独特的突变景观，TP53、RB1 和 PIK3CA 突变富集。它们与传统 UC 的基底分子亚型相关，并可以根据 TP63 及其靶基因表达水平分为上皮-基底和更具临床侵袭性的间充质亚群。其他分析表明，SARC 是由同质粘附基因下调和 EMT 网络失调驱动的，近一半表现出严重浸润的免疫表型。我们的观察结果对这种高度致命的膀胱癌变体的预后和更有效的治疗方法的发展具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be2/6546434/a7ee503b6c29/nihms-1528840-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be2/6546434/70cd1aa8fa3e/nihms-1528840-f0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be2/6546434/426b51c88a09/nihms-1528840-f0004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be2/6546434/b061eabee129/nihms-1528840-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be2/6546434/a7ee503b6c29/nihms-1528840-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be2/6546434/70cd1aa8fa3e/nihms-1528840-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be2/6546434/b2d04745cb3b/nihms-1528840-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be2/6546434/426b51c88a09/nihms-1528840-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be2/6546434/eaec110fbbba/nihms-1528840-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be2/6546434/b061eabee129/nihms-1528840-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be2/6546434/a7ee503b6c29/nihms-1528840-f0007.jpg

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