Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas
| Autor: | A R Denison, S. Nanthakumaran, A Dahle-Smith, Gordon Urquhart, John S. Leeds, G H Bain, Perminder Phull, Fiona J. Gilbert, Andrew Welch, M Finegan, Heike I. Grabsch, Russell D. Petty, Graeme I. Murray, K.M. Matula, Elaina Susan Renata Collie-Duguid, Puay Hoon Tan, Lutz Frank Schweiger, Ian N. Fleming, F McKiddie, K G M Park, Trevor Ahearn |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Esophageal Neoplasms Cell Growth Processes Drug resistance Adenocarcinoma leptin Stomach Neoplasms Gastro Biomarkers Tumor gene expression profiling medicine Humans Neoplasm RNA Messenger predictive biomarker prognostic biomarker Molecular Diagnostics Aged Neoplasm Staging Aged 80 and over business.industry Leptin digestive oral and skin physiology gastro-oesophageal adenocarcinoma Middle Aged Prognosis medicine.disease digestive system diseases Gene expression profiling Oncology Drug Resistance Neoplasm immunohistochemistry Cancer research Female Neoplasm staging Erratum Corrigendum business hormones hormone substitutes and hormone antagonists Chemotherapy resistance |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.2014.45 |
| Popis: | Background: Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy. Methods: Tumour biopsies from patients (n=14) with TNM stage IB–IV gastro-oesophageal adenocarcinomas receiving platinum-based combination chemotherapy were used as a discovery cohort and profiled with Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154) treated with surgery with or without neoadjuvant platinum combination chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for qualification of gene expression profiling results by immunohistochemistry. A cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33, were used for in vitro validation investigations. Results: We identified 520 genes with differential expression (Mann–Whitney U, P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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