POSTER NO: 35

Uncovering Functionally Relevant Signaling Pathways of Esophageal Squamous Cell Carcinoma Using cDNA Microarraay-Based Expression Profiling

¹Aiping Luo, ¹Jianping Kong, ²Gengxi Hu, ¹Xiuqin Wang, ¹Min Wu, ¹Zhihua Liu
¹National Laboratory of Molecular Oncology,Cancer Institute, CAMS, PUMC, Beijing, Chaoyang District, Panjiayuan nanli, P.O. Box 2258, ²Chinese Academy of Sciences Institute of Biochemistry and Cell Biology, Shanghai, China

To elucidate the molecular mechanism of Esophageal Squamous Cell Carcinoma (ESCC) and uncover functionally relevant signaling pathways, esophageal epithelial tissue specimen, prospectively from five ESCC patients, were screened using a cDNA expression array containing gene-specific fragments from normal esophagus and esophageal cancer cDNA libraries. Only those genes with signal differences of more than 3-fold were considered as modulated. Semiquantitative RT-PCR, Northern Blot and immunostaining analysis of a subset of these differentially expressed genes gave results consistent with cDNA microarray. 168 genes (including 88 novel genes) were down-regulated and 21 genes (including 5 novel genes) were up-regulated. With the aid of tools such as cluster analysis and self-organizing maps, the known genes were classified into six groups according to molecular function and cellular components. We proposed that 18 genes associated with epithelial cell terminal differentiation couldn't form the cornified cell envelope (CE) as a physical barrier against the environment, which might contribute to the increased susceptibility toward carcinogens. A gene expression network, including several cytosolic signaling pathways, may also be the molecular mechanism of carcinogenesis that operate in the cell and of the molecular basis and classification of esophageal cancer. Moreover, RHCG, Keratin 17 and ferritin L-chain may be used as new markers for susceptibility to ESCC, and new prognostic markers of methods of predicting response to treatment.

Authors 1 and 2 contributed equally to this study.