Identification of gene expression profiling associated with erlotinib-related skin toxicity in pancreatic adenocarcinoma patients

Octavio Caba; Antonio Irigoyen; Cristina Jimenez-Luna; Manuel Benavides; Francisco M Ortuño; Javier Gallego; Ignacio Rojas; Carmen Guillen-Ponce; Carolina Torres; Enrique Aranda; Jose Prados

doi:10.1016/j.taap.2016.10.003

Identification of gene expression profiling associated with erlotinib-related skin toxicity in pancreatic adenocarcinoma patients

Toxicol Appl Pharmacol. 2016 Nov 15:311:113-116. doi: 10.1016/j.taap.2016.10.003. Epub 2016 Oct 6.

Authors

Affiliations

¹ Department of Health Sciences, University of Jaen, Jaen, Spain. Electronic address: [email protected].
² Department of Medical Oncology, Virgen de la Salud Hospital, Toledo, Spain. Electronic address: [email protected].
³ Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain. Electronic address: [email protected].
⁴ Department of Medical Oncology, Virgen de la Victoria Hospital, Malaga, Spain. Electronic address: [email protected].
⁵ Department of Computer Architecture and Computer Technology, Research Center for Information and Communications Technologies, University of Granada, Granada, Spain. Electronic address: [email protected].
⁶ Department of Medical Oncology, General Universitario de Elche Hospital, Alicante, Spain. Electronic address: [email protected].
⁷ Department of Computer Architecture and Computer Technology, Research Center for Information and Communications Technologies, University of Granada, Granada, Spain. Electronic address: [email protected].
⁸ Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid, Spain. Electronic address: [email protected].
⁹ Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: [email protected].
¹⁰ Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofía Hospital, University of Córdoba, Córdoba, Spain. Electronic address: [email protected].
¹¹ Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain. Electronic address: [email protected].

PMID: 27720938
DOI: 10.1016/j.taap.2016.10.003

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.

Keywords: Erlotinib; Microarray; Pancreatic ductal adenocarcinoma; Skin rash.

MeSH terms

Adenocarcinoma / drug therapy*
Aged
Erlotinib Hydrochloride / adverse effects*
Female
Gene Expression Profiling*
Humans
Male
Middle Aged
Pancreatic Neoplasms / drug therapy*
Skin / drug effects*

Substances

Erlotinib Hydrochloride