RT Journal Article
SR Electronic
T1 Meta-analysis of 1,200 transcriptomic profiles identifies a prognostic model for pancreatic ductal adenocarcinoma
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 355602
DO 10.1101/355602
A1 Vandana Sandhu
A1 Knut Jorgen Labori
A1 Ayelet Borgida
A1 Ilinca Lungu
A1 John Bartlett
A1 Sara Hafezi-Bakhtiari
A1 Rob Denroche
A1 Gun Ho Jang
A1 Danielle Pasternack
A1 Faridah Mbaabali
A1 Matthew Watson
A1 Julie Wilson
A1 Elin H. Kure
A1 Steven Gallinger
A1 Benjamin Haibe-Kains
YR 2018
UL http://biorxiv.org/content/early/2018/06/27/355602.abstract
AB Background With a dismal 8% median 5-year overall survival (OS), pancreatic ductal adenocarcinoma (PDAC) is highly lethal. Only 10-20% of patients are eligible for surgery, and over 50% of these will die within a year of surgery. Identify molecular predictors of early death would enable the selection of PDAC patients at high risk.Methods We developed the Pancreatic Cancer Overall Survival Predictor (PCOSP), a prognostic model built from a unique set of 89 PDAC tumors where gene expression was profiled using both microarray and sequencing platforms. We used a meta-analysis framework based on the binary gene pair method to create gene expression barcodes robust to biases arising from heterogeneous profiling platforms and batch effects. Leveraging the largest compendium of PDAC transcriptomic datasets to date, we show that PCOSP is a robust single-sample predictor of early death (≤1 yr) after surgery in a subset of 823 samples with available transcriptomics and survival data.Results The PCOSP model was strongly and significantly prognostic with a meta-estimate of the area under the receiver operating curve (AUROC) of 0.70 (P=1.9e-18) and hazard ratio (HR) of 1.95(1.6-2.3) (P=2.6e-16) for binary and survival predictions, respectively. The prognostic value of PCOSP was independent of clinicopathological parameters and molecular subtypes. Over-representation analysis of the PCOSP 2619 gene-pairs (1070 unique genes) unveiled pathways associated with Hedgehog signalling, epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) signalling.Conclusion PCOSP could improve treatment decision by identifying patients who will not benefit from standard surgery/chemotherapy and may benefit from alternate approaches.AUROCArea under the receiver operating curveGOGene annotationOSOverall survivalPCOSPPancreatic cancer overall survival predictorPDACPancreatic ductal adenocarcinomaTSPTop scoring pairs.