PT  - JOURNAL ARTICLE
AU  - Katharina Leithner
AU  - Christoph Wohlkoenig
AU  - Elvira Stacher
AU  - Jörg Lindenmann
AU  - Freyja-Maria Smolle-Jüttner
AU  - Helmut H. Popper
AU  - Andelko Hrzenjak
AU  - Andrea Olschewski
AU  - Horst Olschewski
TI  - Expression profiling in hypoxic non-small cell lung cancer explants reveals a four-gene hypoxia signature
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p1964
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p1964.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p1964.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Background: Hypoxia is frequent in solid cancers like lung cancer and contributes to chemotherapy resistance. To identify patients with hypoxic tumors would be of advantage. Direct oxygen measurements are of limited use, thus, feasible hypoxia markers are needed.Material and Methods: A novel ex-vivo model was established using fragmented non-small cell lung cancer (NSCLC) specimens cultured three days under hypoxia (1% oxygen) or normoxia. cDNA microarrays were perfomed on hypoxic and normoxic fragments derived from ten patients (five adenocarcinomas, five squamous cell carcinomas). Correction for multiple testing was performed using FDR5.Results: Histomorphology and viability/apoptosis tests confirmed the viability of the fragments. HIF-1α immunostaining and expression of carbonic anhydrase IX mRNA were increased in hypoxia. Microarray analysis revealed 129 regulated genes with at least two-fold expression change in hypoxia compared to normoxia. Hypoxia-induced gene expression was histology-dependent, only four genes were significantly regulated in both subtypes.Conclusions: Our novel ex-vivo model is suitable to study hypoxic adaptation in lung cancer. Its advantage is the use of real tumor tissue maintained under different oxygen concentrations. cDNA expression profiling revealed a four-gene hypoxia signature that might be useful in therapies aiming to restore tumor perfusion and oxygenation.