A diagnostic marker for superficial urothelial bladder carcinoma: lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression.
A diagnostic marker for superficial urothelial bladder carcinoma: lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression.
复制标题
DOI：
10.1186/s12885-016-2845-5
复制
发表时间：
2016-10-18
期刊：
影响因子：
3.8
通讯作者：
Miura Y
中科院分区：
文献类型：
--
作者：
Kawaguchi M;Hara N;Bilim V;Koike H;Suzuki M;Kim TS;Gao N;Dong Y;Zhang S;Fujinawa Y;Yamamoto O;Ito H;Tomita Y;Naruse Y;Sakamaki A;Ishii Y;Tsuneyama K;Inoue M;Itoh J;Yasuda M;Sakata N;Jung CG;Kanazawa S;Akatsu H;Minato H;Nojima T;Asai K;Miura Y
病理分期和分级对浅表性膀胱尿路上皮癌初次经尿道切除术（TUR）的预后预测能力有限。AT基序结合因子1（ATBF 1）是一种肿瘤抑制性转录因子，通常定位于细胞核，但已在几种癌症的细胞质中检测到。在这里，我们研究了ATBF 1的细胞内定位的诊断价值作为一个标志物，用于识别高危尿路上皮膀胱癌。生成7种抗ATBF 1抗体以覆盖整个ATBF 1序列。构建了4个人流感病毒血凝素衍生氨基酸序列标签的ATBF 1 cDNA表达载体，以KR[X10-12]K为共有序列定位核定位信号（NLS）的功能域。共分析了117份来自人膀胱癌初始TUR的样本。所有患者均未接受过化疗或放疗。ATBF 1的核定位由ATBF 1上的三个NLS协同调节。ATBF 1的胞质片段缺乏NLS。根据ATBF 1阳性核染色将患者分为两组，ATBF 1+（n = 110）和ATBF 1-（n = 7）病例的总生存期（P = 0.021）和膀胱内无复发生存期（P = 0.013）存在显著差异。多变量分析显示，在调整细胞分级和病理分期后，ATBF 1染色是膀胱内无复发生存的独立预后因素（P = 0.008）。ATBF 1的切割导致ATBF 1片段的细胞质定位并下调核ATBF 1。ATBF 1亚细胞定位的改变与尿路上皮癌的恶性特征有关。使用抗ATBF 1抗体的病理学评价能够识别在初始TUR时被忽略的高度恶性病例。ATBF 1的核定位提示尿路上皮癌预后较好。本文的在线版本（doi：10.1186/s12885-016-2845-5）包含补充材料，可供授权用户使用。
Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma. Seven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation. ATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n = 110) and ATBF1− (n = 7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008). Cleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma. The online version of this article (doi:10.1186/s12885-016-2845-5) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
3.8
作者：
Kai K;Zhang Z;Yamashita H;Yamamoto Y;Miura Y;Iwase H
通讯作者：
Iwase H
影响因子：
2.8
作者：
Xu, Junyan;Sauvageot, Jurga;Isaacs, William B.
通讯作者：
Isaacs, William B.
DOI：
10.1016/j.bbrc.2003.12.054
发表时间：
2004-01-30
影响因子：
3.1
作者：
Nojiri, S;Joh, T;Ito, M
通讯作者：
Ito, M
影响因子：
4.8
作者：
MIURA, Y;TAM, T;TAMAOKI, T
通讯作者：
TAMAOKI, T
表皮生长因子诱导最大胶原酶-1（MMP-1）和 T24 膀胱癌细胞恶性特征需要 STAT3 激活
影响因子：
8
作者：
Itoh, M;Murata, T;Yoshida, K
通讯作者：
Yoshida, K