Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1732, USA.
Cancer. 2013 Feb 1;119(3):529-39. doi: 10.1002/cncr.27725. Epub 2012 Aug 22.
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.
同源盒基因 HOXB7 在多种癌症中过度表达，通过对增殖、存活、侵袭和血管生成的不同影响促进肿瘤发生。尽管已发表的基因芯片数据表明 HOXB7 在胰腺导管腺癌（PDAC）中过度表达，但它在胰腺癌中的功能尚未得到研究。
在 PDAC 细胞系和患者样本中以及在正常胰腺中检查 HOXB7 信使和蛋白水平。通过免疫组织化学法确定患者肿瘤中的 HOXB7 蛋白表达，并将其与临床病理因素和生存相关联。通过在 PDAC 细胞系中敲低和过表达来评估 HOXB7 对细胞增殖、生长和侵袭的影响。通过微阵列分析确定 HOXB7 敲低后表达水平改变的候选基因。
与正常胰腺相比，PDAC 细胞系和患者肿瘤样本中的 HOXB7 信使和蛋白水平均显著升高。对 145 例切除的 PDAC 组织微阵列的评估发现，高 HOXB7 蛋白表达与淋巴结转移相关（P =.034），并且在多变量分析中是总体生存的独立预后因素（危险比= 1.56，95%置信区间= 1.02-2.39）。在 PDAC 细胞系中敲低或过表达 HOXB7 分别导致侵袭性表型降低或增加，而不影响增殖或细胞活力。
HOXB7 在 PDAC 中经常过度表达，特别促进侵袭表型，与淋巴结转移和更差的生存结局相关。HOXB7 及其下游靶标可能代表用于抑制 PDAC 的侵袭和转移能力的新型临床生物标志物或治疗靶标。
