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Predictive Values of Gemcitabine Associated Genes in Malignant Effusions

Author: ChenYing
Tutor: QianXiaoPing
School: Nanjing Medical University
Course: Medical Oncology
Keywords: malignant effusions gemcitabine RRM1 hENT1 dCK
CLC: R734.2
Type: Master's thesis
Year: 2011
Downloads: 32
Quote: 0
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Abstract


Objective The aim of this study was to investigate the association of mRNA expression levels of RRM1 (ribonucleotide reductase subunit1) hENT1 (human equilibrative nucleotide transporter1) and dCK (deoxicytidine kinase) with chemosensitivity to gemcitabine in malignant pleural and peritoneal effusions.The purpose was to investigate the predictive role of these biomarkers in the efficacy of gemcitabine-base chemotherapy for patients with malignant effusions.Methods Malignant pleural and peritoneal effusions were collected from 24 patients diagnosed with stageⅣmalignant tumor,prospectively. The tumor cells were isolated and the sensitivity of tumor cells to gemcitabine was detected by CCK-8 assays. Real-time quantitative RT-PCR was used to examine the relative mRNA expression levels of RRM1,hENT1 and dCK in the primary cancer cells. Results Tumor cells isolated from malignant effusions without chemotherapy seemed more sensitive to gemcitabine than those who received chemotherapy before (67.88%vs42.94%,P=0.006); No significant association was found between gene expression and clinicopathologic features(P>0.05);RRM1 mRNA expression levels were inversely correlated with sensitivity to gemcitabine in malignant effusions. Patients with lower RRM1 mRNA expression levels had a higher sensitivity to gemcitabine compared with those with higher expression levels (r=-0.497, P=0. 013). No significant correlation was observed between hENT1 and dCK mRNA expression and sensitivity to gemcitabine(P>0.05).Conclusions We identified correlations between gemcitabine sensitivity and RRM1 mRNA expression levels in primary cancer cells isolated from malignant effusions.Assessing gene expression in primary tumor cells isolated from malignant effusions may be useful in predicting drug sensitivity for patients with malignant effusions,enabling the development of“real-time”individualized chemotherapy for those patients.

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