High gene expression of TS1, GSTP1, and ERCC1 are risk factors for survival in patients treated with trimodality therapy for esophageal cancer.

作者: Mary-Beth Moore Joshi , Yoshinori Shirota , Kathleen D. Danenberg , Debbi H. Conlon , Dennis S. Salonga

DOI: 10.1158/1078-0432.CCR-04-1387

关键词: GSTP1Univariate analysisEsophageal cancerGastroenterologyInternal medicinePathologyEsophageal diseaseERCC1BiopsyProportional hazards modelMedicineProspective cohort study

摘要: Purpose: To assess the relationship between molecular markers associated with chemotherapy resistance and survival in esophageal cancer patients treated trimodality therapy. Experimental Design: The original pretreatment formalin-fixed, paraffin-embedded endoscopic tumor biopsy material was obtained from 99 concurrent cisplatin plus 5-fluorouracil 45 Gy radiation followed by resection at Duke University Medical Center (Durham, NC) 1986 to 1997. cDNA derived analyzed determine mRNA expression relative an internal reference gene ( β-actin ) using fluorescence-based, real-time reverse transcription-PCR. Possible of platinum association [glutathione S -transferase π (GSTP1) excision cross-complementing 1 (ERCC1)] [thymidylate synthase (TS1)] were measured. Results : Cox proportional hazards model revealed a significant inverse, linear effect for TS1 respect P = 0.007). An inverse treatment response also detected ≤ 0.001). Univariate analysis identified decreased GSTP1 ≥ 3.0 0.05). In multivariate analyses, >6.0, ERCC1 >3, >3 statistically predictors Additionally, presence >3.0 or >6.0 ∼2-fold increase risk recurrence 0.086 0.003, respectively). Conclusion measurement chemoresistance biopsies may be useful tool assessing outcome trimodality-treated cancer. These data should validated further larger prospective studies.

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