Gene expression profiling of 1200 pancreatic ductal adenocarcinoma reveals novel subtypes

BMC Cancer
Lan ZhaoHong Yan

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related death in the world with a five-year survival rate of less than 5%. Not all PDAC are the same, because there exist intra-tumoral heterogeneity between PDAC, which poses a great challenge to personalized treatments for PDAC. To dissect the molecular heterogeneity of PDAC, we performed a retrospective meta-analysis on whole transcriptome data from more than 1200 PDAC patients. Subtypes were identified based on non-negative matrix factorization (NMF) biclustering method. We used the gene set enrichment analysis (GSEA) and survival analysis to conduct the molecular and clinical characterization of the identified subtypes, respectively. Six molecular and clinical distinct subtypes of PDAC: L1-L6, are identified and grouped into tumor-specific (L1, L2 and L6) and stroma-specific subtypes (L3, L4 and L5). For tumor-specific subtypes, L1 (~ 22%) has enriched carbohydrate metabolism-related gene sets and has intermediate survival. L2 (~ 22%) has the worst clinical outcomes, and is enriched for cell proliferation-related gene sets. About 23% patients can be classified into L6, which leads to intermediate survival and is enriched for lipid and protein met...Continue Reading

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Datasets Mentioned

BETA
GSE79670
GSE62165
GSE62452
GSE57495
GSE60980
GSE77858
GSE55643
GSE71729

Methods Mentioned

BETA
3
RNA-Seq
biopsies

Software Mentioned

ClaNC
SAM ( Significance Analysis of Microarrays )
TCGA2STAT R package
H2O
NMF R
NMF package
ComBat
limma
Ensembl
pheatmap R

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