Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy. Integrative analysis shows that signaling pathways driving epithelial-to-mesenchymal transition and insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1R) pathway are highly activated in MP subtype tumors. Importantly, MP subtype cancer cells are more sensitive to inhibition of IGF1/IGF1R pathway than EP subtype. Detailed characterization of these two subtypes could identify novel therapeutic targets and useful biomarkers for prognosis and therapy response.

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Colorectal cancer in African Americans has an increased incidence and mortality relative to Whites. The mean age of CRC development in African Americans is younger than that of Whites. There is also evidence for a more proximal colonic distribution of cancers and adenomas in African Americans. African Americans are less likely to have undergone diagnostic testing and screening for colorectal cancer. Special efforts are needed to improve colorectal cancer screening participation rates in African Americans. Clinical gastroenterologists should play an active role in educating the public and primary care physicians about special issues surrounding colorectal cancer in African Americans. Community healthcare groups and gastrointestinal specialists should develop culturally sensitive health education programs for African Americans regarding colorectal cancer. The high incidence and younger age at presentation of colorectal cancer in African Americans warrant initiation of colorectal cancer screening at the age 45 yr rather than 50 yr.

BackgroundDespite many attempts to establish pre-treatment prognostic markers to understand the clinical biology of esophageal adenocarcinoma (EAC), validated clinical biomarkers or parameters remain elusive. We generated and analyzed tumor transcriptome to develop a practical biomarker prognostic signature in EAC.Methodology/Principal FindingsUntreated esophageal endoscopic biopsy specimens were obtained from 64 patients undergoing surgery and chemoradiation. Using DNA microarray technology, genome-wide gene expression profiling was performed on 75 untreated cancer specimens from 64 EAC patients. By applying various statistical and informatical methods to gene expression data, we discovered distinct subgroups of EAC with differences in overall gene expression patterns and identified potential biomarkers significantly associated with prognosis. The candidate marker genes were further explored in formalin-fixed, paraffin-embedded tissues from an independent cohort (52 patients) using quantitative RT-PCR to measure gene expression. We identified two genes whose expression was associated with overall survival in 52 EAC patients and the combined 2-gene expression signature was independently associated with poor outcome (P<0.024) in the multivariate Cox hazard regression analysis.Conclusions/SignificanceOur findings suggest that the molecular gene expression signatures are associated with prognosis of EAC patients and can be assessed prior to any therapy. This signature could provide important improvement for the management of EAC patients.

EUS with FNA is useful for detection of malignancy in a pancreatic mass. The procedure appears to have a complication rate of 2%. Impact of this technique on clinical management of patients needs further evaluation.