comparative membranome expression analysis in primary tumors and derived cell lines比较membranome表达式分析原发性肿瘤和派生的细胞系.pdf

Comparative Membranome Expression Analysis in Primary Tumors and Derived Cell Lines 1 2 1 3 3 3 Paolo Uva , Armin Lahm , Andrea Sbardellati , Anita Grigoriadis , Andrew Tutt , Emanuele de Rinaldis * 1 CRS4 Bioinformatics Laboratory, Parco Scientifico e Tecnologico POLARIS, Pula, Cagliari, Italy, 2 IRBM, Pomezia, Rome, Italy, 3 Breakthrough Breast Cancer Research Unit, King’s College London School of Medicine, Guy’s Hospital, London, United Kingdom Abstract Despite the wide use of cell lines in cancer research, the extent to which their surface properties correspond to those of primary tumors is poorly characterized. The present study addresses this problem from a transcriptional standpoint, analyzing the expression of membrane protein genes - the Membranome – in primary tumors and immortalized in-vitro cultured tumor cells. 409 human samples, deriving from ten independent studies, were analyzed. These comprise normal tissues, primary tumors and tumor derived cell lines deriving from eight different tissues: brain, breast, colon, kidney, leukemia, lung, melanoma, and ovary. We demonstrated that the Membranome has greater power than the remainder of the transcriptome when used as input for the automatic classification of tumor samples. This feature is maintained in tumor derived cell lines. In most cases primary tumors show maximal similarity in Membranome expression with cell lines of same tissue origin. Differences in Membranome expression between tumors and cell lines were analyzed also at the pathway level and biological themes were identified that were differentially regulated in the two settings. Moreover, by including normal samples in the analysis, we quantified