Role of HOXB7 in regulation of progression and metastasis of human lung adenocarcinoma

Dysregulation of homeobox B7 (HOXB7), a member of the homeobox genes family, was suggested to play a role in regulation of tumorigenesis and metastases of some cancers. However, the functions of HOXB7 in association with lung adenocarcinoma (LAC) have not been investigated. The correlation between the level of HOXB7 expression and cancer progression in patients is not known. In this study, through analysis of 75 LAC samples and their corresponding normal lung epithelium tissues immunohistochemistry (IHC), we demonstrate that HOXB7 was overexpressed in LAC specimens compared to their paired normal lung epithelium tissues. Increased expression of HOXB7 was associated with poor clinical outcomes, correlating significantly with a short survival time in patients who had LAC. Moreover, HOXB7 expression level was correlated with the tumor status (P = 0.028), nodal status (P = 0.012) and tumor stage (P = 0.029) in lung adenocarcinoma. Silencing HOXB7 inhibited cell growth and metastases in vitro and in vivo. In conclusion, our results suggest that HOXB7 promotes LAC progression by enhancing proliferation and metastasis. The increased expression of HOXB7 in LAC is a potential prognostic indicator for patients, and HOXB7 could be a novel target for treatment of LAC patients. © 2013 Wiley Periodicals, Inc.

[1]  L. Kowalski,et al.  HOXB7 expression is a prognostic factor for oral squamous cell carcinoma , 2012, Histopathology.

[2]  J. Zucman‐Rossi,et al.  The HOX gene network in hepatocellular carcinoma , 2011, International journal of cancer.

[3]  A. Neri,et al.  Overexpression of HOXB7 and homeobox genes characterizes multiple myeloma patients lacking the major primary immunoglobulin heavy chain locus translocations , 2011, American journal of hematology.

[4]  A. Nicholson,et al.  Non-small-cell lung cancer , 2011, The Lancet.

[5]  D. Duboule,et al.  A genetic approach to the transcriptional regulation of Hox gene clusters. , 2011, Annual review of genetics.

[6]  G. Botti,et al.  The HOX genes network in uro-genital cancers: mechanisms and potential therapeutic implications. , 2011, Current medicinal chemistry.

[7]  D. Wellik.  Hox genes and kidney development , 2011, Pediatric Nephrology.

[8]  C. Moran.  Importance of molecular features of non-small cell lung cancer for choice of treatment. , 2011, The American journal of pathology.

[9]  X. Bian,et al.  HOXB7 as a Prognostic Factor and Mediator of Colorectal Cancer Progression , 2011, Clinical Cancer Research.

[10]  D. Ribatti,et al.  HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients , 2011, Leukemia.

[11]  S. Tsim,et al.  Staging of non-small cell lung cancer (NSCLC): a review. , 2010, Respiratory medicine.

[12]  G. Narla,et al.  Lung adenocarcinoma: lessons in translation from bench to bedside. , 2010, The Mount Sinai journal of medicine, New York.

[13]  K. Azuma,et al.  [Molecular targeted therapy in lung cancer]. , 2010, Nihon rinsho. Japanese journal of clinical medicine.

[14]  M. Rastegar,et al.  Epigenetic control of Hox genes during neurogenesis, development, and disease. , 2010, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[15]  Saraswati Sukumar,et al.  The Hox genes and their roles in oncogenesis , 2010, Nature Reviews Cancer.

[16]  Satoshi Kondo,et al.  Aberrant expressions of HOX genes in colorectal and hepatocellular carcinomas. , 2010, Oncology reports.

[17]  M. Lopes,et al.  Overexpression of HOXB7 homeobox gene in oral cancer induces cellular proliferation and is associated with poor prognosis. , 2009, International journal of oncology.

[18]  E. Sánchez-Herrero,et al.  Function and specificity of Hox genes. , 2009, The International journal of developmental biology.

[19]  S. Gettinger.  Targeted therapy in advanced non-small-cell lung cancer. , 2008, Seminars in respiratory and critical care medicine.

[20]  C. Zahnow,et al.  Hoxb7 inhibits transgenic HER-2/neu-induced mouse mammary tumor onset but promotes progression and lung metastasis. , 2008, Cancer research.

[21]  O. Pourquié,et al.  Hox genes in time and space during vertebrate body formation , 2007, Development, growth & differentiation.

[22]  Y. Miyagi,et al.  Dikkopf-1 as a novel serologic and prognostic biomarker for lung and esophageal carcinomas. , 2007, Cancer research.

[23]  P. Laird,et al.  The Role of DNA Methylation in the Development and Progression of Lung Adenocarcinoma , 2007, Disease markers.

[24]  Xinyan Wu,et al.  HOXB7, a homeodomain protein, is overexpressed in breast cancer and confers epithelial-mesenchymal transition. , 2006, Cancer research.

[25]  H. Naora,et al.  Homeobox gene expression in cancer: insights from developmental regulation and deregulation. , 2005, European journal of cancer.

[26]  Yoko Takahashi,et al.  Aberrant expression of HOX genes in human invasive breast carcinoma. , 2005, Oncology reports.

[27]  J. C. Hombría,et al.  Beyond homeosis--HOX function in morphogenesis and organogenesis. , 2003, Differentiation; research in biological diversity.

[28]  T. Svingen,et al.  Altered HOX Gene Expression in Human Skin and Breast Cancer Cells , 2003, Cancer biology & therapy.

[29]  M. L. R. D. Christenson,et al.  International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma , 2012 .

[30]  C. Shen.  DEREGULATED HOMEOBOX GENE EXPRESSION IN CANCER: CAUSE OR CONSEQUENCE? , 2002 .