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. 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Insuk Sohn 

PROVIDER: E-GEOD-26253 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress