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

• Published in: British journal of cancer Vol. 98; no. 4; pp. 832 - 839
• Main Authors: Matsubara, J, Nishina, T, Yamada, Y, Moriwaki, T, Shimoda, T, Kajiwara, T, Nakajima, T E, Kato, K, Hamaguchi, T, Shimada, Y, Okayama, Y, Oka, T, Shirao, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.02.2008; Nature Publishing Group
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor; Biomedical and Life Sciences; Biomedicine; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Cancer Research; Chemotherapy, Adjuvant; Cisplatin - administration & dosage; Dihydrouracil Dehydrogenase (NADP) - genetics; Dihydrouracil Dehydrogenase (NADP) - metabolism; Disease Progression; DNA Primers - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drug Combinations; Drug Resistance; Endonucleases - genetics; Endonucleases - metabolism; Epidemiology; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - metabolism; Middle Aged; Molecular Diagnostics; Molecular Medicine; Oncology; Oxonic Acid - administration & dosage; Prognosis; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Survival Rate; Tegafur - administration & dosage; excision repair cross-complementing gene 1; dihydropyrimidine dehydrogenase; gastric cancer; prognostic factor; epidermal growth factor receptor
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604211

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.