HOXB7 promotes invasion and predicts survival in pancreatic adenocarcinoma.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1732, USA.
Anne
A
Nguyen Kovochich
Michael
M
Arensman
Anna R
AR
Lay
Nagesh P
NP
Rao
Timothy
T
Donahue
Xinmin
X
Li
Samuel W
SW
French
David W
DW
Dawson
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D011379:Prognosis; D016019:Survival Analysis; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
D014408:Biomarkers, Tumor; C490538:HOXB7 protein, human; D018398:Homeodomain Proteins