Gene expression analysis for predicting gemcitabine sensitivity in pancreatic cancer patients

Current in vitro drug sensitivity tests have limitations and disadvantages. This study investigated the use of gene expression data to predict the sensitivity of pancreatic cancers to gemcitabine.

Cancer cells isolated from 14 pancreatic cancer patients were tested in vitro for gemcitabine sensitivity using the collagen droplet drug sensitivity test (CD-DST). On the basis of this test, 9 of the 14 cancers were identified as either gemcitabine-sensitive or gemcitabine-resistant. Total RNA was extracted from each of those nine cancers and used as a template to synthesize Cy3-labeled cDNA. Pancreatic RNA extracted from six normal individuals was used as a control. Labeled probes were hybridized to an Atlas Glass Human 1.0 Microarray chip, after which the chips were washed and scanned, and the data were analyzed using Microsoft Excel-embedded software. The expression profiles of selected genes were confirmed using real-time PCR analysis.

Statistical analysis of the microarray data showed that four genes were differentially expressed in gemcitabine-sensitive cancers: microsomal glutathione S-transferase 1 (GSTT1), topoisomerase II alpha (TOP2A), caspase 3, and ATP-binding cassette and subfamily C member 2 (ABCC2). More than 20 other genes were additionally identified as possible candidate genes associated with drug resistance.

Expression of drug resistance-related genes appeared to predict whether a cancer was gemcitabine-sensitive or -resistant. Further study will enable a drug resistance scoring system to be established on the basis of gene expression. Such a system will allow more efficient application of chemotherapy.