Preliminary data of Non- Small Cell Lung Cancer gene expression pilot study Tõnu Vooder, Kristjan Välk, Andres Metspalu Genoa 2005

Introduction 1 milj. deaths in a year 5 year survival 5-15% In Estonia ~ 700 cases every year ~70 radical treatments in TU Hospital every year With the same hist. type and stage different patients have different treatment response and disease progression New possibility in lung cancer diagnostics- microarray gene expression analysis

Histological classification of lung cancer Lung Cancer Small Cell Lung Cancer Lung CancerNon-Small Cell Lung Cancer Squamous cell lung cancer Adeno-carcinoma Giant cell carcinoma

Epidemiology Rare disease at the beginning of 20 century In 1950 the relationship between the cigarette smoke and lung cancer cigarette smoke increases relative risk for 20 times 95% of lung cancer patients are smokers 10% smokers will have lung cancer Radon and asbestos

TissueTotal RNA AAA Cy3/Cy5 cRNAHybridisation Microarray detection Analysis Normalisation, Ratio statistics

Lung Cancer gene expression studies so far … Possible to distinguish small and non-small cell lung cancer, different subtypes and different molecular phenotypes in them Associations between differentiation and clinical outcome Proliferative cluster (lung and breast cancer, Chung 2002), in silico found in different cancers First and second response genes

Patient Cancer type Patient Nr. Age and gender SmokingTNMStage BA548M 10 pypT2N0M0 Ib BA2873M 50 pypT2N1M0 IIa BA4764M 18 pypT1N0M0 Ia BA5755M 35 pypT2N0M0 Ib BA5874M 40 pypT1N0M0 Ia BA838M 25 pypT2N3M0 IIIb A2152M 35 pypT1N0M0 Ia A3755M 30 pypT2N0M0 Ib A4061N 20 pypTNM1pul IV A5661M 40 pypT2N0M0 Ib

Differentially expressed genes 314 genes, which were at least 2 times ↨ regulated at least in three tumours 52 ↑ genes (30 without annotation) and 262 ↓ genes (146 without annotation) 43↓ and 5↑ genes, which had by annotation direct or indirect association with inflammation, tumorigenic processes

STEAP, DAPK1, EDG1 STEAP- Six Transmembrane Epithelial Antigen of the Prostate. Tumour specific cell surface marker. Therapy and diagnostics DAPK1- Death-Associated Protein Kinase 1, + mediator in y int. induced cell death signal pathway EDG1- Estrogen Down-regulated Gene 1, ↓, ↓ in breast cancer. If artificially ↑= proliferation restricted

A40A40 A40 A40R A37 A37R BA28 BA28R BA47 BA47R A21 A21R A56 BA57 A56R BA57R BA58 BA58R BA5 BA5R BA8 BA8R

Summary and perspectives 314 ↨ genes, 48 associated with tumours (by annotation) 3 clusters Distinguish metastases tumour Analysis of 100 different histological lung cancer samples - diagnostic TEST SNP analysis

Acknowledgments! Estonian Science FoundationEstonian Science Foundation Estonian BiocentreEstonian Biocentre