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Gene expression profiling of formalin fixed paraffin embedded tumor tissue identifies gastric cancer patients who are at high risk after curative surgery plus adjuvant chemoradiotherapy

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE26253 | GEO | 2014/03/01

SECONDARY ACCESSION(S): PRJNA135085

REPOSITORIES: GEO

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Gene expression profiling of formalin fixed paraffin embedded tumor tissue identifies gastric cancer patients who are at high risk after curative surgery plus adjuvant chemoradiotherapy

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.

2014-03-01 | E-GEOD-26253 | biostudies-arrayexpress

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2016-06-20 | PXD002903 | Pride

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Project description:Samples were taken from colorectal cancers in surgically resected specimens in 36 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for molecular markers for predicting recurrence. Keywords: repeat Thirty-six colorectal cancer patients who had undergone surgical resection of colorectal cancer were studied. In all patients, curative resection was performed and no patients had any distant metastasis at the time of operation (stage III patients). Among the 36 patients, 23 patients did not develop recurrence. On the other hand, 13 patients developed rucurrence such as liver metastases, lung metastases and distant lymph node metastases. The median follow up period was 4.5 years.

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Gene expression signature-based novel prognostic risk score in gastric cancer

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MicroRNA signature to predict the response of adjuvant chemotherapy in patients with stage II & III colorectal cancer

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FGF19-FGFR4 promotes the progression of gallbladder carcinoma in a biliary autocrine pathway dependent on GPBAR1-EGR1 axis

Project description:GBC is the most common type of biliary tract cancers and the seventh most common gastrointestinal cancer. Most patients are diagnosed as GBC in an unresectable stage because of the silent symptoms. Even after curative surgery, most patients undergo recurrence due to the early metastasis and limited adjuvant therapies. All these reasons lead to an extremely dismal prognosis of advanced GBC, with a 5-year survival rate approximately 5%-10%. Cholestasis has been shown to be an important factor in the malignant progression of gallbladder cancer. In this study, we stimulate GBC-SD cells with high concentration of CDCA to simulate cholestasis and analyzed the DEGs in the stimulation of CDCA.

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