Expression profiling of angiogenesis-related genes in brain metastases of lung cancer and melanoma.
Brain metastases (BM) are the most common brain tumors of adults and are associated with fatal prognosis. Formation of new blood vessels, named angiogenesis, was proposed to be the main hallmark of the growth of BM. Previous preclinical evidence revealed that angiogenic blockage might be considered for treatment; however, there were varying responses. In this study, we aimed to characterize the expression pattern of angiogenesis-related genes in BM of lung cancer and melanoma, which might be of importance for the different responses against anti-angiogenic treatment. Fifteen snap-frozen tissues obtained from BM of non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and melanoma patients were analyzed for angiogenesis-related genes using a commercially available gene expression kit. Epilepsy tissue was used as control. Expression values were analyzed using hierarchical clustering investigating relative fold changes and mapping to Omicsnet protein interaction network. CXCL10, CEACAM1, PECAM1, KIT, COL4A2, COL1A1, and HSPG2 genes were more than 50-fold up-regulated in all diagnosis groups when compared to control, whereas genes such as ANGPT4, PDGFRB, and SERPINF1 were down-regulated only in SCLC and melanoma groups, respectively. Using hierarchical clustering, 12 out of 15 cases were allocated to the correct histological primary tumor type. We identified genes with consistent up-regulation in BM of lung cancer and melanoma and other genes with differential expression across BM of these tumor types. Our data may be of relevance for targeted therapy or prophylaxis of BM using anti-angiogenic agents.
Department of Medicine 1, Medical University of Vienna, Vienna, Austria.|Central Nervous System Tumour Unit, Comprehensive Cancer Center Vienna, Vienna, Austria.
Aysegül
A
Ilhan-Mutlu
Department of Biomedical Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria.
Christian
C
Siehs
Department of Medicine 1, Medical University of Vienna, Vienna, Austria.|Central Nervous System Tumour Unit, Comprehensive Cancer Center Vienna, Vienna, Austria.
Anna Sophie
AS
Berghoff
Institute for Neurology, Medical University of Vienna, Vienna, Austria.
Gerda
G
Ricken
Department of Neuro-Surgery, Medical University of Vienna, Vienna, Austria.|Central Nervous System Tumour Unit, Comprehensive Cancer Center Vienna, Vienna, Austria.
Georg
G
Widhalm
Department of Medicine III, Medical University of Vienna, Vienna, Austria.|Central Nervous System Tumour Unit, Comprehensive Cancer Center Vienna, Vienna, Austria.
Ludwig
L
Wagner
Department of Medicine 1, Medical University of Vienna, Vienna, Austria. matthias.preusser@meduniwien.ac.at.|Central Nervous System Tumour Unit, Comprehensive Cancer Center Vienna, Vienna, Austria. matthias.preusser@meduniwien.ac.at.|Department of Medicine I and Comprehensive Cancer Center, Central Nervous System Tumours Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. matthias.preusser@meduniwien.ac.at.
Matthias
M
Preusser
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000473:pathology; D015854:Up-Regulation
Angiogenesis; Brain metastases; Melanoma; Non-small cell lung cancer; Omicsnet; Small-cell lung cancer