Expression profiles of non-small cell lung cancers on cDNA microarrays: identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs.

To investigate genes involved in pulmonary carcinogenesis and those related to sensitivity of nonsmall cell lung cancers (NSCLCs) to therapeutic drugs, we performed cDNA microarray analysis of 37 NSCLCs after laser-capture microdissection of cancer cells from primary tumors. A clustering algorithm applied to the expression data easily distinguished two major histological types of non-small cell lung cancer, adenocarcinoma and squamous cell carcinoma. Subsequent analysis of the 18 adenocarcinomas identified 40 genes whose expression levels could separate cases with lymph-node metastasis from those without metastasis. In addition, we compared the expression data with measurements of the sensitivity of surgically dissected NSCLC specimens to six anti-cancer drugs (docetaxel, paclitaxel, irinotecan, cisplatin, gemcitabine, and vinorelbine), as measured by the CD-DST (collagen gel droplet embedded culture-drug sensitivity test) method. We found significant associations between expression levels of dozens of genes and chemosensitivity of NSCLCs. Our results provide valuable information for eventually identifying predictive markers and novel therapeutic target molecules for this type of cancer.