Cyclooxygenase-2-Associated Factors and Gastric Carcinogenesis Mechanisms-Clinical Association and Genomic Investigation

Background: Gastric carcinoma (GC) remains among the most frequent malignancies in Taiwan as well as in the world and also one of leading causes of cancer-related death. Accumulating evidence shows that chronic inflammation leads to the occurrence of cancers, including GC, via multiple mechanisms. Cyclooxygenase-2 (COX-2) is a crucial enzyme in inflammatory process and is shown to be up-regulated in a variety of cancers. Therefore, COX-2 may play an important role in carcinogenesis. The hallmarks of cancer include continuing proliferation, evading apoptosis, prohibiting immunity, promoting angiogenesis, enhancing invasion and metastasis. We hypothesize that COX-2 induces carcinogenesis through multiple mechanistic strategies and interactions of multiple genes simultaneously. Laser capture microdissection (LCM) for obtaining pure cancer cells and microarray technology and analysis are now generally accepted as powerful tools in genomic research, providing reliable microdissection of cancer cells and simultaneous analysis of whole genome. Aim: Use microarray technology to investigate patterns of genomic change related to differential COX-2 expression and their clinicopathological association in GC. Materials: GC cell lines are transfected with COX-2-expressing vector to establish cell lines with differential levels of COX-2 expression. Clinical specimens are obtained from surgical resection of GC proved by pathology at the Surgical Department of National Taiwan University Hospital, which COX-2 expression is evaluated by Western blotting and immunohistochemical staining. Methods: The present project will use microarray for analysis of genome clustering patterns of surgical tissue (GC cells procured by LCM) and GC cell lines based on differential COX-2 expression levels, to discover significantly positively or negatively associated gene clusterings which contain candidate genes for studies of carcinogenesis mechanisms and establishment of animal experiment mode