| Experiment ID | EXP00137 |
| Reference | Title: Integrative survival-based molecular profiling of human pancreatic cancer. Author: Donahue TR, Tran LM, Hill R, Li Y, Kovochich A, Calvopina JH, Patel SG, Wu N, Hindoyan A, Farrell JJ, Li X, Dawson DW, Wu H. Journal: Clin Cancer Res. 2012 Mar 1;18(5):1352-63. doi: 10.1158/1078-0432.CCR-11-1539.Epub 2012 Jan 18. Abstract: PURPOSE: To carry out an integrative profile of human pancreatic ductaladenocarcinoma (PDAC) to identify prognosis-significant genes and their relatedpathways.EXPERIMENTAL DESIGN: A concordant survival-based whole genome in silico arrayanalysis of DNA copy number, and mRNA and miRNA expression in 25 early-stage PDACwas carried out. A novel composite score simultaneously integrated geneexpression with regulatory mechanisms to identify the signature genes with themost levels of prognosis-significant evidence. The predominant signaling pathwayswere determined via a pathway-based approach. Independent patient cohorts (n =148 and 42) were then used as in vitro validation of the array findings.RESULTS: The composite score identified 171 genes in which expressions were able to define two prognosis subgroups (P = 3.8e-5). Eighty-eight percent (151 of 171)of the genes were regulated by prognosis-significant miRNAs. The phosphoinositide3-kinase/AKT pathway and SRC signaling were densely populated byprognosis-significant genes and driven by genomic amplification of SRC and miRNA regulation of p85α and CBL. On tissue microarray validation (n = 148), p85αprotein expression was associated with improved survival for all patients (P =0.02), and activated P-SRC (Y418) was associated shorter survival for patientswith low-grade histology tumors (P = 0.04). Interacting P-SRC and p85α revealedthat they define two distinct PDAC patient subgroups (P = 0.0066). Furthering theimportance of these pathways, CBL protein expression was associated with improvedsurvival (P = 0.03) on a separate cohort (n = 42).CONCLUSIONS: These pathways and related genes may represent putative clinicalbiomarkers and possible targets of individualized therapy in the distinct patientsubgroups they define. PMID: 22261810 |
| Expressiion Profile | Description: Integrative Survival-Based Molecular Profiling of Human Pancreatic Cancer [miRNA] Organism: Homo sapiens GEO ID: GSE32678 Platform: GPL7723 Number of samples: 32 |
| Design and Sample | Cancer Type: pancreatic cancer Cancer SubType: N/D Cell Line: N/D Experimental Design: cancer vs normal Case Sample: pancreatic cancer Control Sample: non-malignant pancreas sample Num of Case: 25 Num of Control: 7 Quantification Software: Limma Num of miRNAs: 836 |
| Identification | Num of Up: 26 Num of Down: 19 |