Project description:Purpose: Our study aimed to disclose the specific gene expression profile representing peritoneal relapses inherent in primary gastric cancers and to identify patients at high risk of peritoneal relapse in a prospective study on the basis of the molecular prediction. Experimental Design: RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly we constructed molecular prediction system and validated the robustness and prognostic validity of the analysis by 500 times multiple random sampling in 56 retrospective set consisting of 38 relapse free and 18 peritoneal relapse patients. Secondly we applied this prediction to 85 prospective set to assess the predictive accuracy and prognostic validity. Results: In retrospective phase, 500 times multiple random sampling analysis yielded 68% predictive accuracy in average and 22 gene expression profile associated with peritoneal relapse was identified. This prediction could identify significantly poor prognostic patients. In prospective phase, the molecular prediction yielded 76.9% overall accuracy. KaplanâMeier analysis with peritoneal relapse free survival showed a significant difference between âgood signature groupâ and âpoor signature groupâ (Log-rank p=0.0017). Multivariate analysis by Cox regression hazards model revealed that the molecular prediction was the only independent peritoneal relapse prognostic factor. Conclusions: Gene expression profile inherent in primary gastric cancer tissues can be useful to predict peritoneal relapse prospectively after curative surgery and individualize postoperative management to improve the prognosis of advanced gastric cancers. Of 141 samples, 56 represented the retrospective phase and 85 represented the prospective phase.
Project description:Purpose: Our study aimed to disclose the specific gene expression profile representing peritoneal relapses inherent in primary gastric cancers and to identify patients at high risk of peritoneal relapse in a prospective study on the basis of the molecular prediction. Experimental Design: RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly we constructed molecular prediction system and validated the robustness and prognostic validity of the analysis by 500 times multiple random sampling in 56 retrospective set consisting of 38 relapse free and 18 peritoneal relapse patients. Secondly we applied this prediction to 85 prospective set to assess the predictive accuracy and prognostic validity. Results: In retrospective phase, 500 times multiple random sampling analysis yielded 68% predictive accuracy in average and 22 gene expression profile associated with peritoneal relapse was identified. This prediction could identify significantly poor prognostic patients. In prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis with peritoneal relapse free survival showed a significant difference between ‘good signature group’ and ‘poor signature group’ (Log-rank p=0.0017). Multivariate analysis by Cox regression hazards model revealed that the molecular prediction was the only independent peritoneal relapse prognostic factor. Conclusions: Gene expression profile inherent in primary gastric cancer tissues can be useful to predict peritoneal relapse prospectively after curative surgery and individualize postoperative management to improve the prognosis of advanced gastric cancers.
Project description:Anatomical staging is a critical, although imperfect, instrument to assess gastric cancer prognosis and define indication for surgery and adjuvant therapy. Despite recent advances, treatment results, as a whole, remain less than satisfactory. Thus, biomarkers are sorely needed to improve risk categorization and define new molecular targets for therapy. We used microarrays to identify genes differentially expressed according to prognosis of the patients. A cohort of 15 patients was prospectively identified with a histological diagnosis of gastric adenocarcinoma, submitted to surgery with curative intent. Two prognostic patient groups were defined, according to overall survival (short x long), with a 24 month cut-off. These groups were matched by known prognostic factors: TNM staging, histological subtype (intestinal/diffuse) and gender.
Project description:Gastric cancer is the second most common cause of cancer-related death worldwide. Up to 80% of patients who undergo curative surgical resection develop locoregional or distant recurrence. A recent large-scaled meta-analysis on 3,838 patients from 17 trials has demonstrated survival benefit from adjuvant chemotherapy when compared to surgery alone. Furthermore, INT-0116 study has demonstrated a survival benefit from postoperative chemoradiation therapy with 5-fluorouracil and leucovorin in gastric cancer patients. Despite these advances, 5-year disease-free survival rates remain poor for patients diagnosed with stage III or IV gastric cancer (stage IIIA, 57.6%, stage IIIB, 39.6%; and stage IV 26.3%) underscoring the need for development of new targeted agents. On the other hand those diagnosed with stage Ib/II gastric cancer have moderate 5 year recurrence rate (76.2%) and suggest the presence of significant molecular heterogeneity with varying prognosis. We hypothesized that gene expression of profiling of formalin fixed paraffin embedded tumor (FFPET) samples using whole genome cDNA-mediated Annealing, Selection, Extension, and Ligation (WG-DASL) assay could be used to develop robust prognostic profiles for gastric cancer treated with chemoradiotherapy that are independent of clinicopathological features. We have identified and validated a gene expression signature that predicts recurrence after curative resection. We also performed pathway analyses to delineate aberrant pathways in aggressive gastric cancer which suggest targeted treatment strategies.
Project description:Gastric cancer is the second most common cause of cancer-related death worldwide. Up to 80% of patients who undergo curative surgical resection develop locoregional or distant recurrence. A recent large-scaled meta-analysis on 3,838 patients from 17 trials has demonstrated survival benefit from adjuvant chemotherapy when compared to surgery alone. Furthermore, INT-0116 study has demonstrated a survival benefit from postoperative chemoradiation therapy with 5-fluorouracil and leucovorin in gastric cancer patients. Despite these advances, 5-year disease-free survival rates remain poor for patients diagnosed with stage III or IV gastric cancer (stage IIIA, 57.6%, stage IIIB, 39.6%; and stage IV 26.3%) underscoring the need for development of new targeted agents. On the other hand those diagnosed with stage Ib/II gastric cancer have moderate 5 year recurrence rate (76.2%) and suggest the presence of significant molecular heterogeneity with varying prognosis. We hypothesized that gene expression of profiling of formalin fixed paraffin embedded tumor (FFPET) samples using whole genome cDNA-mediated Annealing, Selection, Extension, and Ligation (WG-DASL) assay could be used to develop robust prognostic profiles for gastric cancer treated with chemoradiotherapy that are independent of clinicopathological features. We have identified and validated a gene expression signature that predicts recurrence after curative resection. We also performed pathway analyses to delineate aberrant pathways in aggressive gastric cancer which suggest targeted treatment strategies. RNA was extracted from 2-4 sections of 4-μm thick, FFPET sections. Non-tumor elements were removed by manual microdissection before transfer to the extraction tube guided by hematoxylin and eosin stained slides. The samples with RNA concentrations of <40 ng/μL, A260/A280 ratios <1.5 or A260/230 ratios <1.0 were considered as inadequate samples and were excluded from the analysis.
Project description:Peritoneal carcinomatosis is a frequent finding in patients with primary gastric cancer, and it is associated with a poor prognosis. A major mechanism in peritoneal carcinomatosis is the dissemination of cancer cells into the abdominal cavity, mainly in diffuse gastric adenocarcinoma. The features that enable diffuse primary gastric tumours to develop peritoneal dissemination have been little investigated and are only incompletely understood. We therefore compared the gene expression profile in patients with diffuse primary gastric cancer with and without peritoneal carcinomatosis. Specimens from consecutive gastric cancer patients with and without peritoneal carcinomatosis were investigated using oligonucleotide microarrays. Keywords: Disease state analysis
Project description:We obtained snap-frozen tissue samples from 20 colorectal cancer (CRC) patients with stage III disease who had undergone curative resection. The expression profiles were determined using Affymetrix Human Genome U133Plus 2.0 arrays. We used microarrays to identify potential gene deregulation correlated with the outcomes of colon cancer patients. mRNA from 20 primary colorectal tumour samples were extracted and hybridized to HG-U133Plus 2.0 expression arrays. The NexusExp3 procedure was used to make calls of expression. Of the 20 patients, 7 had disease relapse within 3 years after surgery.
Project description:This SuperSeries is composed of the following subset Series: GSE27854: Overexpression of NUCKS1 in colorectal cancer correlates with recurrence after curative surgery (gene expression analysis) GSE27910: Overexpression of NUCKS1 in colorectal cancer correlates with recurrence after curative surgery (copy number analysis) Refer to individual Series