Prediction of chemosensitivity for patients with advanced gastric cancer by DNA misroarray analysis, using specimens obtained from fine needle aspiration biopsy.

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Global gene expression profiling by microarrays has been used as a valuable tool for the identification of prognostic and predictive marker genes. Even though this technology is now wide spread and relatively standardized, there are only few data available which compare responders with non-responders in chemotherapy. We conducted phase I and II clinical studies of weekly paclitaxel and 5'-DFUR in patients with unresectable or recurrent gastric cancer. Response rate of this regimen was 50%. It is important to predict the chemosensitivity, because half of the patients showed no effect to these agents. Therefore we analyzed gene expression data of pretreatment biopsies of gastric cancer patients and compared responders with non-responders. To establish a method to predict the response of gastric cancer patients to chemotherapy, we used a genome-wide DNA microarray to analyze 24 biopsy samples of advanced gastric cancer from 20 patients who had been treated with an identical protocol of pa … More clitaxel and 5'-DFUR. Eight of 24 samples were obtained from fine needle aspiration biopsy by endoscopic ultrasonography.RNA was isolated and expression profiling performed using Affymetrix U133 plus2 Array. Two thirds of the biopsies yielded sufficient amounts of RNA for expression profiling and high quality data were obtained for 16 samples of 14 patients. In the samples obtained from fine needle aspiration biopsy, 6 (75%) of 8 samples yielded sufficient amounts of RNA. We analyzed 14 samples of 14 patients who were consisted of 7 responders and 7 non-responders. To filter genes out of the 54675,we first investigate all genes for which p-call were present, and selected 958 genes. We next investigate 958 genes for which mean average differences were>2-fold between responders and non-responders. We used the Fisher ratio to evaluate separatability between responders and non-responders. Thirty-nine genes whose expression differed significantly between 7 responders and 7 non-responders were identified. Thirty-seven genes were up-regulated and two genes were down-regulated in responders. Less