title: Identification of gene expression profiling associated with erlotinib-related skin toxicity in pancreatic adenocarcinoma patients.
abstract: Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that showed activity against pancreatic ductal adenocarcinoma (PDAC). The drug's most frequently reported side effect as a result of EGFR inhibition is skin rash (SR), a symptom which has been associated with a better therapeutic response to the drug. Gene expression profiling can be used as a tool to predict which patients will develop this important cutaneous manifestation. The aim of the present study was to identify which genes may influence the appearance of SR in PDAC patients. The study included 34 PDAC patients treated with erlotinib: 21 patients developed any grade of SR, while 13 patients did not (controls). Before administering any chemotherapy regimen and the development of SR, we collected RNA from peripheral blood samples of all patients and studied the differential gene expression pattern using the Illumina microarray platform HumanHT-12 v4 Expression BeadChip. Seven genes (FAM46C, IFITM3, GMPR, DENND6B, SELENBP1, NOL10, and SIAH2), involved in different pathways including regulatory, migratory, and signalling processes, were downregulated in PDAC patients with SR. Our results suggest the existence of a gene expression profiling significantly correlated with erlotinib-induced SR in PDAC that could be used as prognostic indicator in this patients.
authors.affiliation: Department of Health Sciences, University of Jaen, Jaen, Spain. Electronic address: ocaba@ujaen.es.
authors.forename: Octavio
authors.initials: O
authors.lastname: Caba
authors.affiliation: Department of Medical Oncology, Virgen de la Salud Hospital, Toledo, Spain. Electronic address: antonioirigoyen@yahoo.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Irigoyen
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain. Electronic address: crisjilu@ugr.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Jimenez-Luna
authors.affiliation: Department of Medical Oncology, Virgen de la Victoria Hospital, Malaga, Spain. Electronic address: manuel.benavides.sspa@juntadeandalucia.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Benavides
authors.affiliation: Department of Computer Architecture and Computer Technology, Research Center for Information and Communications Technologies, University of Granada, Granada, Spain. Electronic address: fortuno@ugr.es.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Ortuño
authors.affiliation: Department of Medical Oncology, General Universitario de Elche Hospital, Alicante, Spain. Electronic address: j.gallegoplazas@gmail.com.
authors.forename: Javier
authors.initials: J
authors.lastname: Gallego
authors.affiliation: Department of Computer Architecture and Computer Technology, Research Center for Information and Communications Technologies, University of Granada, Granada, Spain. Electronic address: irojas@ugr.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Rojas
authors.affiliation: Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid, Spain. Electronic address: carmen.guillen@salud.madrid.org.
authors.forename: Carmen
authors.initials: C
authors.lastname: Guillen-Ponce
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: ctorres@uic.edu.
authors.forename: Carolina
authors.initials: C
authors.lastname: Torres
authors.affiliation: Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofía Hospital, University of Córdoba, Córdoba, Spain. Electronic address: enrique.aranda@imibic.org.
authors.forename: Enrique
authors.initials: E
authors.lastname: Aranda
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain. Electronic address: jcprados@ugr.es.
authors.forename: Jose
authors.initials: J
authors.lastname: Prados
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D012867:Skin / Q000187:drug effects*
chemical_list: D000069347:Erlotinib Hydrochloride
keywords: Erlotinib; Microarray; Pancreatic ductal adenocarcinoma; Skin rash