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膀胱癌分子分类的临床应用实用性和上皮-间充质转化的附加价值：波形蛋白表达的预后价值。

Practicability of clinical application of bladder cancer molecular classification and additional value of epithelial-to-mesenchymal transition: prognostic value of vimentin expression.

机构信息

Cancer Biology and Epigenetics Group IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.

Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.

出版信息

J Transl Med. 2020 Aug 5;18(1):303. doi: 10.1186/s12967-020-02475-w.

DOI:10.1186/s12967-020-02475-w
PMID:32758253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7405371/
Abstract

BACKGROUND

Bladder cancer (BlCa) taxonomy has proved its impact in patient outcome and selection for targeted therapies, but such transcriptomic-based classification has not yet translated to routine practice. Moreover, epithelial-to-mesenchymal transition (EMT) has shown relevance in acquisition of more aggressive BlCa phenotype. We aimed to test the usefulness of the molecular classification, as defined by immunohistochemistry (a routinely performed and easy-to-implement technique), in a well-defined BlCa cohort of both non-muscle invasive (NMIBC) and muscle invasive (MIBC) disease. Also, we aimed to assess the additional prognostic value of the mesenchymal marker vimentin to the stratification strategy.

METHODS

A total of 186 samples were available. Immunohistochemistry/RT-qPCR for luminal markers GATA3/FOXA1, basal markers KRT5/KRT6A and vimentin were performed.

RESULTS

mRNA expression levels of the markers positively correlated with immunoexpression scores. We found substantial overlapping in immunoexpression of luminal and basal markers, evidencing tumor heterogeneity. In MIBC, basal tumors developed recurrence more frequently. NMIBC patients with higher vimentin immunoexpression endured poorer disease-free survival, and increased expression was observed from normal bladder-NMIBC-MIBC-metastases.

CONCLUSIONS

The classification has the potential to be implemented in routine, but further adjustments in practical scoring should be defined; focusing on additional markers, including those related to EMT, may further refine BlCa molecular taxonomy.

摘要

背景

膀胱癌 (BlCa) 分类学已证明其对患者预后和靶向治疗选择的影响，但这种基于转录组的分类尚未转化为常规实践。此外，上皮-间充质转化 (EMT) 已显示与获得更具侵袭性的 BlCa 表型有关。我们旨在通过免疫组织化学（一种常规进行且易于实施的技术）测试分子分类在明确的非肌肉浸润性 (NMIBC) 和肌肉浸润性 (MIBC) BlCa 队列中的有用性。此外，我们旨在评估间充质标志物波形蛋白对分层策略的额外预后价值。

方法

共获得 186 个样本。进行了用于腔标志物 GATA3/FOXA1、基底标志物 KRT5/KRT6A 和波形蛋白的免疫组化/RT-qPCR。

结果

标志物的 mRNA 表达水平与免疫表达评分呈正相关。我们发现腔和基底标志物的免疫表达存在大量重叠，表明肿瘤异质性。在 MIBC 中，基底肿瘤更频繁地复发。具有较高波形蛋白免疫表达的 NMIBC 患者无病生存率较差，并且在正常膀胱-NMIBC-MIBC-转移过程中观察到表达增加。

结论

该分类有可能在常规中实施，但在实际评分中应进一步调整；关注包括 EMT 相关标志物在内的其他标志物可能会进一步细化 BlCa 分子分类。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13cd/7405371/1c4d052f256d/12967_2020_2475_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13cd/7405371/2025f70b63ac/12967_2020_2475_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13cd/7405371/e57487310c72/12967_2020_2475_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13cd/7405371/489171e9a626/12967_2020_2475_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13cd/7405371/6afd3482ec74/12967_2020_2475_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13cd/7405371/1c4d052f256d/12967_2020_2475_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13cd/7405371/2025f70b63ac/12967_2020_2475_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13cd/7405371/e57487310c72/12967_2020_2475_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13cd/7405371/489171e9a626/12967_2020_2475_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13cd/7405371/6afd3482ec74/12967_2020_2475_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13cd/7405371/1c4d052f256d/12967_2020_2475_Fig5_HTML.jpg

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