title: HOX D13 expression across 79 tumor tissue types.
abstract: HOX genes control normal development, primary cellular processes and are characterized by a unique genomic network organization. Locus D HOX genes play an important role in limb generation and mesenchymal condensation. Dysregulated HOXD13 expression has been detected in breast cancer, melanoma, cervical cancer and astrocytomas. We have investigated the epidemiology of HOXD13 expression in human tissues and its potential deregulation in the carcinogenesis of specific tumors. HOXD13 homeoprotein expression has been detected using microarray technology comprising more than 4,000 normal and neoplastic tissue samples including 79 different tumor categories. Validation of HOXD13 expression has been performed, at mRNA level, for selected tumor types. Significant differences are detectable between specific normal tissues and corresponding tumor types with the majority of cancers showing an increase in HOXD13 expression (16.1% normal vs. 57.7% cancers). In contrast, pancreas and stomach tumor subtypes display the opposite trend. Interestingly, detection of the HOXD13 homeoprotein in pancreas-tissue microarrays shows that its negative expression has a significant and adverse effect on the prognosis of patients with pancreatic cancer independent of the T or N stage at the time of diagnosis. Our study provides, for the first time, an overview of a HOX protein expression in a large series of normal and neoplastic tissue types, identifies pancreatic cancer as one of the most affected by the HOXD13 hoemoprotein and underlines the way homeoproteins can be associated to human cancerogenesis.
authors.affiliation: Department of Clinical & Experimental Medicine, Federico II University Medical School, Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cantile
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Adrienne
authors.initials: A
authors.lastname: Tschan
authors.forename: Daniel
authors.initials: D
authors.lastname: Baumhoer
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.forename: Giulia
authors.initials: G
authors.lastname: Schiavo
authors.forename: Iris
authors.initials: I
authors.lastname: Forte
authors.forename: Michel
authors.initials: M
authors.lastname: Bihl
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Liguori
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Eva
authors.initials: E
authors.lastname: Karamitopoulou-Diamantis
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Clemente
authors.initials: C
authors.lastname: Cillo
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; D035683:MicroRNAs; D014157:Transcription Factors