Differential Gene Expression in Erlotinib-treated Fibroblasts.

Differential Gene Expression in Erlotinib-treated Fibroblasts.

Nurs Res. 2018 Dec 12;:

Authors: Wickersham KE, Hodges TK, Edelman MJ, Song Y, Nan M, Dorsey SG

Abstract
BACKGROUND: Therapies targeting the epidermal growth factor receptor (EGFR) result in a painful rash, the most common and debilitating toxicity among patients with non-small cell lung cancer (NSCLC) who take EGFR tyrosine kinase inhibitor (TKI) therapy; however, predicting the development and the severity of the rash is difficult.
OBJECTIVE: To examine how erlotinib-an EGFR TKI that NSCLC patients take to stop or slow tumor growth-altered the transcriptome of dermal fibroblasts.
METHODS: Dermal fibroblasts (ATCC® PCS-201-012™) were seeded in cell culture flasks, grown under standard conditions, and transferred to cell culture dishes. Cells were treated once daily for three days with erlotinib 100nM (n = 5), erlotinib 1μM (n = 5), vehicle 1μM (DMSO) (n = 5), or no treatment (n = 5). Total RNA was extracted using a standard TRIzol® method and hybridized using Affymetrix GeneChip® Human Genome U133 Plus 2.0 arrays. Raw intensities generated from the arrays were normalized using Robust Multi-array Average method and analyzed using ANOVA in Limma R software. Differentially expressed genes were analyzed using Ingenuity Pathway Analysis to identify canonical or noncanonical signaling pathways enriched in this dataset.
RESULTS: We selected genes for investigation based on their potential role in wound healing (AQP3), rash development (CCL2), fibroblast activation (PALLD), cancer and cancer progression (GDF-15, SLC7A11, MMP12, DIRAS3), and cell cycle control (CDC6). We were able to validate four of these genes by both Western blot analysis and qPCR (MMP12, CCL2, CDC6, and SLC7A11).
DISCUSSION: If found predictive of rash in future studies using patient samples, our findings may help to identify those at risk for severe rash so that (a) the dose of EGFR TKI therapy may be adjusted; (b) additional treatments for the rash can be developed; and/or (c) precise, patient-centered interventions can be developed so that patients with cancer can better self-manage their rash and adhere to EGFR TKI treatment.

PMID: 30540703 [PubMed - as supplied by publisher]

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