British journal of cancer, 2015-09, Vol.113 (6), p.878-885
2015
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- Autor(en) / Beteiligte
- Titel
- TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients
- Ist Teil von
- British journal of cancer, 2015-09, Vol.113 (6), p.878-885
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor β activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma. TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT-PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma. In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively). The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0007-0920eISSN: 1532-1827DOI: 10.1038/bjc.2015.283Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4578082
- Format
- –
- Schlagworte
- Adenocarcinoma - metabolism, Adenocarcinoma - pathology, Adenocarcinoma - therapy, Aged, Antineoplastic Combined Chemotherapy Protocols - therapeutic use, Apoptosis, Apoptosis - drug effects, Apoptosis - radiation effects, Baculoviral IAP Repeat-Containing 3 Protein, Biomarkers, Cancer therapies, Carcinoma, Squamous Cell - metabolism, Carcinoma, Squamous Cell - pathology, Carcinoma, Squamous Cell - therapy, Cell Line, Tumor, Chemoradiotherapy - methods, Cisplatin - administration & dosage, Down-Regulation, Drug Resistance, Neoplasm, Esophageal Neoplasms - metabolism, Esophageal Neoplasms - pathology, Esophageal Neoplasms - therapy, Esophagogastric Junction, Female, Fluorouracil - administration & dosage, Growth factors, Humans, In Vitro Techniques, Inhibitor of Apoptosis Proteins - genetics, Inhibitor of Apoptosis Proteins - metabolism, Kinases, Male, MAP Kinase Kinase Kinases - antagonists & inhibitors, MAP Kinase Kinase Kinases - physiology, Medical research, Middle Aged, Neoplasm Proteins - genetics, Neoplasm Proteins - metabolism, Oncology, Pancreatic cancer, Proteins, Radiation therapy, Radiation Tolerance, RNA, Messenger - metabolism, ROC Curve, Sodium, Surgery, Taxoids - administration & dosage, Translational Therapeutics, Tumors, Ubiquitin-Protein Ligases - genetics, Ubiquitin-Protein Ligases - metabolism, Zearalenone - analogs & derivatives, Zearalenone - pharmacology