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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adolescent
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Adult
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Aged
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Aged, 80 and over
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Biomarkers, Tumor
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Camptothecin / administration & dosage
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Camptothecin / analogs & derivatives
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Chemotherapy, Adjuvant
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Cisplatin / administration & dosage
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DNA Primers / chemistry
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Dihydrouracil Dehydrogenase (NADP) / genetics*
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Dihydrouracil Dehydrogenase (NADP) / metabolism
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Disease Progression
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Drug Combinations
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Endonucleases / genetics*
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Endonucleases / metabolism
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ErbB Receptors / genetics*
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ErbB Receptors / metabolism
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Irinotecan
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Male
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Methylenetetrahydrofolate Reductase (NADPH2) / genetics
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Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
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Middle Aged
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Oxonic Acid / administration & dosage
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Prognosis
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Stomach Neoplasms / drug therapy*
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Stomach Neoplasms / metabolism*
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Stomach Neoplasms / pathology
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Survival Rate
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Tegafur / administration & dosage
Substances
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Biomarkers, Tumor
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DNA Primers
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DNA-Binding Proteins
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Drug Combinations
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RNA, Messenger
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S 1 (combination)
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Tegafur
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Oxonic Acid
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Irinotecan
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Dihydrouracil Dehydrogenase (NADP)
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Methylenetetrahydrofolate Reductase (NADPH2)
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ErbB Receptors
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ERCC1 protein, human
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Endonucleases
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Cisplatin
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Camptothecin