Prognostic significance of pre B cell leukemia transcription factor 2 (PBX2) expression in non-small cell lung carcinoma

Prognostic significance of pre B cell leukemia transcription factor 2 (PBX2) expression in non-small cell lung carcinoma
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DOI:
10.1111/j.1349-7006.2009.01156.x
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发表时间:
2009-07-01
期刊:
影响因子:
5.7
通讯作者:
Aozasa, Katsuyuki
Aozasa, Katsuyuki
中科院分区:
医学2区
文献类型:
--
作者:
Qiu, Ying;Morii, Eiichi;Aozasa, Katsuyuki

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前期对乳腺癌细胞系的研究表明,前B细胞白血病转录因子1(PBX 1)是一种与肿瘤侵袭和转移有关的含缬氨肽蛋白(VCP)的转录因子。在非小细胞肺癌(NSCLC)细胞系中,检测了PBX 1和与PBX 1高度同源的转录因子PBX 2对VCP表达的作用。在A549和PC 14 NSCLC细胞系中用siRNA检测PBX 1和PBX 2对VCP表达的影响。应用免疫组化方法检测206例NSCLC组织中PBX 2和VCP的表达水平并进行比较。随后,评估PBX表达在NSCLC患者临床行为中的意义。在NSCLC细胞系中,当PBX 2而非PBX 1表达被敲低时,VCP mRNA的表达水平显著降低。免疫组化结果显示,临床标本中PBX 2与VCP的染色强度相关。分析PBX 2表达与NSCLC患者临床行为的相关性。单因素分析显示,高水平的PBX 2和VCP表达是总体生存率和无病生存率的不良指标。多因素分析显示,VCP高表达是独立的预后因素,而PBX 2不是。PBX 2是NSCLC中VCP的转录因子。由于PBX 2高表达与NSCLC的预后相关,因此PBX 2可能成为治疗NSCLC的靶分子。(Cancer Sci 2009; 100:1198-1209)
Previous studies on the mammary carcinoma cell line have shown that the pre B cell leukemia transcription factor 1 (PBX1) was a transcription factor for valosin-containing protein (VCP), which is involved in invasion and metastasis of cancers. The roles of PBX1 and PBX2, a highly homologous transcription factor to PBX1, for expression of VCP were examined in the cell lines from non-small cell lung cancer (NSCLC). The effects of PBX1 and PBX2 on VCP expression were examined with siRNA in A549 and PC14 NSCLC cell lines. Expression levels of PBX2 and VCP were immunohistochemically examined and compared with each other in 206 NSCLC cases. Subsequently, significance of PBX expression in clinical behavior of NSCLC patients was evaluated. Expression levels of VCP mRNA significantly decreased when PBX2 but not PBX1 expression was knocked down in NSCLC cell lines. Immunohistochemically, staining intensity of PBX2 was correlated with that of VCP in clinical samples. Then correlation of PBX2 expression and clinical behavior of NSCLC patients was evaluated. Univariate analysis revealed high expression levels of PBX2 and VCP to be poor prognosticators for overall and disease-free survival. Multivariate analysis revealed that high expression of VCP but not PBX2 to be an independent prognostic factor. PBX2 is a transcription factor for VCP in NSCLC. Because high levels of PBX2 expression correlated with prognosis of NSCLC, PBX2 could be a target molecule for treatment of NSCLC. (Cancer Sci 2009; 100: 1198-1209)