首页> 美国卫生研究院文献>International Journal of Molecular Sciences >mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants
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mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants

机译:KRT5和KRT20的mRNA表达定义了与组织学变异相关的肌肉浸润性膀胱癌的不同预后亚组

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摘要

Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan®-based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort ( + ) was performed. High expression of KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for KRT5 high: 58%; 5-year DSS for KRT20 high: 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20+/KRT5, 5-year DSS 0%, p < 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high: 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20+/KRT tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested).
机译:最近,肌肉浸润性膀胱癌(MIBC)已通过基因表达谱分类,对治疗反应和患者预后产生重大影响。我们测试了是否可以通过角蛋白5(KRT5)和角蛋白20(KRT20)的mRNA检测来确定MIBC的这些复杂分子亚型。应用基于TaqMan ®的检测方法,对122例经治疗的MIBC患者(中位年龄为68.0岁)进行了逆转录酶定量聚合酶链反应(RT-qPCR),以定量KRT5和KRT20的基因表达。此外,还对MD安德森癌症中心(MDACC)队列(+)进行了计算机分析。 KRT5的高表达和KRT20的低表达与无复发生存率(RFS)和疾病特异性生存率疾病特异性生存率显着提高有关(DSS:KRT5的5年DSS高:58%; KRT20的5年DSS高:29%)。 KRT5和KRT20与淋巴管浸润和淋巴结转移率有关。 KRT5和KRT20的组合可以识别出预后非常差的患者(KRT20 + / KRT5 -,五年DSS 0%,p <0.0001)。在对独立MDACC队列的计算机分析中得出了一致的结果(KRT20低与高的5年DSS:84%对40%, p = 0.042)。高表达 KRT20 的肿瘤以及 KRT20 + / KRT -肿瘤明显富含侵袭性尿路上皮癌变体(微乳头状,浆细胞样,巢状)。

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