Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer.

Abstract	Using laser-captured microdissection and a real-time RT-PCR assay, we quantitatively evaluated mRNA levels of the following biomarkers in paraffin-embedded gastric cancer (GC) specimens obtained by surgical resection or biopsy: excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), epidermal growth factor receptor (EGFR), and five other biomarkers related to anticancer drug sensitivity. The study group comprised 140 patients who received first-line chemotherapy for advanced GC. All cancer specimens were obtained before chemotherapy. In patients who received first-line S-1 monotherapy (69 patients), low MTHFR expression correlated with a higher response rate (low: 44.9% vs high: 6.3%; P=0.006). In patients given first-line cisplatin-based regimens (combined with S-1 or irinotecan) (43 patients), low ERCC1 correlated with a higher response rate (low: 55.6% vs high: 18.8%; P=0.008). Multivariate survival analysis of all patients demonstrated that high ERCC1 (hazard ratio (HR): 2.38 (95% CI: 1.55-3.67)), high DPD (HR: 2.04 (1.37-3.02)), low EGFR (HR: 0.34 (0.20-0.56)), and an elevated serum alkaline phosphatase level (HR: 1.00 (1.001-1.002)) were significant predictors of poor survival. Our results suggest that these biomarkers are useful predictors of clinical outcomes in patients with advanced GC.
Authors	J Matsubara, T Nishina, Y Yamada, T Moriwaki, T Shimoda, T Kajiwara, T E Nakajima, K Kato, T Hamaguchi, Y Shimada, Y Okayama, T Oka, K Shirao
Journal	British journal of cancer (Br J Cancer) Vol. 98 Issue 4 Pg. 832-9 (Feb 26 2008) ISSN: 0007-0920 [Print] England
PMID	18231104 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Biomarkers, Tumor DNA Primers DNA-Binding Proteins Drug Combinations RNA, Messenger S 1 (combination) Tegafur Oxonic Acid Irinotecan Dihydrouracil Dehydrogenase (NADP) Methylenetetrahydrofolate Reductase (NADPH2) ErbB Receptors ERCC1 protein, human Endonucleases Cisplatin Camptothecin
Topics	Adenocarcinoma (drug therapy, metabolism, pathology) Adolescent Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols (therapeutic use) Biomarkers, Tumor Camptothecin (administration & dosage, analogs & derivatives) Chemotherapy, Adjuvant Cisplatin (administration & dosage) DNA Primers (chemistry) DNA-Binding Proteins (genetics, metabolism) Dihydrouracil Dehydrogenase (NADP) (genetics, metabolism) Disease Progression Drug Combinations Endonucleases (genetics, metabolism) ErbB Receptors (genetics, metabolism) Female Gene Expression Regulation, Neoplastic Humans Irinotecan Male Methylenetetrahydrofolate Reductase (NADPH2) (genetics, metabolism) Middle Aged Oxonic Acid (administration & dosage) Prognosis RNA, Messenger (genetics, metabolism) Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms (drug therapy, metabolism, pathology) Survival Rate Tegafur (administration & dosage)

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