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HOXB7 promotes invasion and predicts survival in pancreatic adenocarcinoma
Article first published online: 22 AUG 2012
Copyright © 2012 American Cancer Society
Volume 119, Issue 3, pages 529–539, 1 February 2013
How to Cite
Nguyen Kovochich, A., Arensman, M., Lay, A. R., Rao, N. P., Donahue, T., Li, X., French, S. W. and Dawson, D. W. (2013), HOXB7 promotes invasion and predicts survival in pancreatic adenocarcinoma. Cancer, 119: 529–539. doi: 10.1002/cncr.27725
- Issue published online: 22 JAN 2013
- Article first published online: 22 AUG 2012
- Manuscript Accepted: 24 MAY 2012
- Manuscript Revised: 8 MAY 2012
- Manuscript Received: 24 JAN 2012
- pancreatic adenocarcinoma;
- homeobox genes
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. Cancer 2013. © 2012 American Cancer Society.