High TEAD4 Expression is Associated With Aggressive Clear Cell Renal Cell Carcinoma, Regardless of YAP1 Expression.

IF 1.3 4区 医学 Q3 ANATOMY & MORPHOLOGY
Min A Park, Yeong Heon Lee, Mi-Jin Gu
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引用次数: 0

Abstract

Yes-associated protein 1 (YAP1) and transcriptional coactivator TEA domain transcription factor 4 (TEAD4) are the main effectors of the Hippo signaling pathway. Deregulation of the Hippo signaling pathway significantly impacts tumorigenesis and tumor progression. We evaluated the mRNA expression level of YAP1 and TEAD4 using the Gene Expression Profiling Interactive Analysis database and investigated the roles of YAP1 and TEAD4 in 349 surgically resected clear cell renal cell carcinoma (CCRCC) samples through immunohistochemical analysis. High YAP1 and TEAD4 expression were observed in 57 (16.3%) and 131 (37.5%) cases, respectively. High YAP1 expression was associated with a low nuclear grade only. High TEAD4 expression was significantly associated with large tumor size, high nuclear grade, lymphovascular invasion, advanced pT classification, advanced clinical stage, sarcomatous differentiation, and metastasis. CCRCC with YAP1-low/TEAD4-high expression was significantly associated with aggressive clinicopathological variables and poor outcomes. For CCRCC, higher tumor stage, sarcomatous differentiation, and metastasis were the independent prognostic factors for overall survival (OS) and disease-free survival (DFS). High TEAD4 expression was significantly associated with short OS and DFS but was not an independent prognostic factor. High TEAD4 and YAP1-low/TEAD4-high expression significantly correlated with adverse clinicopathological factors and worse OS and DFS in patients with CCRCC. YAP1 expression was not significantly associated with clinicopathological factors or patient survival. Therefore, TEAD4 plays a critical role in CCRCC tumor progression independent of YAP1 and may be a potential biomarker and therapeutic target for CCRCC.

TEAD4的高表达与侵袭性透明细胞肾细胞癌相关,而与YAP1的表达无关。
是相关蛋白1(YAP1)和转录辅激活因子TEA结构域转录因子4(TEAD4)是Hippo信号通路的主要影响因子。Hippo信号通路的失调显著影响肿瘤发生和肿瘤进展。我们使用基因表达谱交互分析数据库评估YAP1和TEAD4的mRNA表达水平,并通过免疫组织化学分析研究YAP1和TEAD4在349例手术切除的透明细胞肾细胞癌(CCRCC)样本中的作用。YAP1和TEAD4的高表达分别在57例(16.3%)和131例(37.5%)中观察到。YAP1的高表达仅与低核分级相关。TEAD4的高表达与肿瘤大小大、细胞核分级高、淋巴血管浸润、晚期pT分类、晚期临床分期、肉瘤分化和转移显著相关。YAP1低/TEAD4高表达的CCRCC与侵袭性临床病理变量和不良预后显著相关。对于CCRCC,较高的肿瘤分期、肉瘤分化和转移是总生存期(OS)和无病生存期(DFS)的独立预后因素。TEAD4的高表达与短OS和DFS显著相关,但不是一个独立的预后因素。高TEAD4和YAP1低/TEAD4高表达与CCRC患者的不良临床病理因素以及较差的OS和DFS显著相关。YAP1的表达与临床病理因素或患者生存率无显著相关性。因此,TEAD4在独立于YAP1的CCRCC肿瘤进展中起着关键作用,并且可能是CCRCC的潜在生物标志物和治疗靶点。
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来源期刊
Applied Immunohistochemistry & Molecular Morphology
Applied Immunohistochemistry & Molecular Morphology ANATOMY & MORPHOLOGY-MEDICAL LABORATORY TECHNOLOGY
CiteScore
3.20
自引率
0.00%
发文量
153
期刊介绍: ​Applied Immunohistochemistry & Molecular Morphology covers newly developed identification and detection technologies, and their applications in research and diagnosis for the applied immunohistochemist & molecular Morphologist. Official Journal of the International Society for Immunohistochemisty and Molecular Morphology​.
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