HOXB7 promotes invasion and predicts survival in pancreatic adenocarcinoma.
HOXB7 promotes invasion and predicts survival in pancreatic adenocarcinoma.
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DOI：
10.1002/cncr.27725
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发表时间：
2013-02-01
期刊：
影响因子：
6.2
通讯作者：
Dawson, David W.
中科院分区：
文献类型：
--
作者：
Anne Nguyen Kovochich;Arensman, Michael;Lay, Anna R.;Rao, Nagesh P.;Donahue, Timothy;Li, Xinmin;French, Samuel W.;Dawson, David W.
同源盒基因HOXB7在一系列癌症中过度表达，并通过对增殖、存活、侵袭和血管生成的不同影响促进肿瘤的发生。尽管已发表的微阵列数据显示HOXB7在胰腺导管腺癌(PDAC)中过表达，但其在胰腺癌中的作用尚未被研究。在PDAC细胞系和患者样本以及正常胰腺中检测HOXB7消息和蛋白水平。采用免疫组织化学方法检测HOXB7蛋白在肿瘤组织中的表达，并与临床病理因素及生存期进行相关性分析。通过在PDAC细胞系中的敲除和过表达来评估HOXB7对细胞增殖、生长和侵袭的影响。通过微阵列分析确定HOXB7基因敲除后表达水平改变的候选基因。与正常胰腺相比，在PDAC细胞系和患者肿瘤标本中HOXB7的消息和蛋白水平显著升高。对145例切除的PDAC组织芯片的评估发现，HOXB7蛋白的高表达与淋巴结转移相关(P=0.034)，多因素分析显示HOXB7蛋白高表达是总体生存较差的独立预测因素(危险比=1.56，95%可信区间=1.02-2.39)。在PDAC细胞系中，HOXB7基因表达下调或过表达分别导致侵袭力降低或增加，而不影响细胞增殖或细胞存活率。HOXB7在PDAC中经常过表达，特异性促进侵袭性表型，并与淋巴转移和预后不良有关。HOXB7及其下游靶点可能代表了抑制PDAC侵袭和转移能力的新的临床生物标志物或治疗靶点。
The homeobox gene HOXB7 is overexpressed across a range of cancers and promotes tumorigenesis through varying effects on proliferation, survival, invasion, and angiogenesis. Although published microarray data suggest HOXB7 is overexpressed in pancreatic ductal adenocarcinoma (PDAC), its function in pancreatic cancer has not been studied. HOXB7 message and protein levels were examined in PDAC cell lines and patient samples, as well as in normal pancreas. HOXB7 protein expression in patient tumors was determined by immunohistochemistry and correlated with clinicopathologic factors and survival. The impact of HOXB7 on cell proliferation, growth, and invasion was assessed by knockdown and overexpression in PDAC cell lines. Candidate genes whose expression levels were altered following HOXB7 knockdown were determined by microarray analysis. HOXB7 message and protein levels were significantly elevated in PDAC cell lines and patient tumor samples relative to normal pancreas. Evaluation of a tissue microarray of 145 resected PDACs found high HOXB7 protein expression was correlated with lymph node metastasis (P = .034) and an independent predictor of worse overall survival in multivariate analysis (hazard ratio = 1.56, 95% confidence interval = 1.02–2.39). HOXB7 knockdown or overexpression in PDAC cell lines resulted in decreased or increased invasion, respectively, without influencing proliferation or cell viability. HOXB7 is frequently overexpressed in PDAC, specifically promotes invasive phenotype, and is associated with lymph node metastasis and worse survival outcome. HOXB7 and its downstream targets may represent novel clinical biomarkers or targets of therapy for inhibiting the invasive and metastatic capacity of PDAC.
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HOXB7 作为结直肠癌进展的预后因素和调节因子
影响因子：
11.5
作者：
Liao, Wen-Ting;Jiang, Dan;Ding, Yan-Qing
通讯作者：
Ding, Yan-Qing
DOI：
10.1073/pnas.071594398
发表时间：
2001-03-27
影响因子：
11.1
作者：
Naora, H;Yang, Y;Roden, RBS
通讯作者：
Roden, RBS
影响因子：
6
作者：
Liu, N;Furukawa, T;Tsao, MS
通讯作者：
Tsao, MS
影响因子：
4.8
作者：
Grützmann, R;Pilarsky, C;Saeger, HD
通讯作者：
Saeger, HD
DOI：
10.1084/jem.20111102
发表时间：
2011-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li M;Mukasa A;Inda MM;Zhang J;Chin L;Cavenee W;Furnari F
通讯作者：
Furnari F