Genome-wide Analysis of Three-way Interplay Among Gene Expression, Cancer Cell Invasion and Anti-cancer Compound Sensitivity

Abstract

Tumor metastasis is the major cause of cancer death. Although cancer cells exhibit a wide range of invasion ability, a genome-wide portrait about the contributing molecular factors to the heterogeneity is lacking. Tumor cells also exhibit a wide range of sensitivity to anticancer compounds. We conducted an invasion assay on the panel of NCI-60 cell lines and integrated our data with NCI’s compound sensitivity database to find genes associated with both invasion and chemosensitivity. We obtained a unique eight-gene signature for effective prediction of three compounds, paclitaxel, docetaxel and dasatinib. We demonstrated that the eight-gene signature succeeded in predicting the outcome of chemotherapy patients for both lung cancer and breast cancer. The discovery of predictive markers for cancer chemotherapy remains critical toward improving the efficacy of cancer treatment. Our findings might be useful for development of personalized cancer therapy.