RT Journal Article
SR Electronic
T1 Comprehensive genomic meta-analysis identifies intra-tumoural stroma as a predictor of survival in patients with gastric cancer
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1100
OP 1111
DO 10.1136/gutjnl-2011-301373
VO 62
IS 8
A1 Yonghui Wu
A1 Heike Grabsch
A1 Tatiana Ivanova
A1 Iain Beehuat Tan
A1 Jacinta Murray
A1 Chia Huey Ooi
A1 Alexander Ian Wright
A1 Nicholas P West
A1 Gordon G A Hutchins
A1 Jeanie Wu
A1 Minghui Lee
A1 Julian Lee
A1 Jun Hao Koo
A1 Khay Guan Yeoh
A1 Nicole van Grieken
A1 Bauke Ylstra
A1 Sun Young Rha
A1 Jaffer A Ajani
A1 Jae Ho Cheong
A1 Sung Hoon Noh
A1 Kiat Hon Lim
A1 Alex Boussioutas
A1 Ju-Seog Lee
A1 Patrick Tan
YR 2013
UL http://gut.bmj.com/content/62/8/1100.abstract
AB Objective Gastric adenocarcinoma (gastric cancer, GC) is a major cause of global cancer mortality. Identifying molecular programmes contributing to GC patient survival may improve our understanding of GC pathogenesis, highlight new prognostic factors and reveal novel therapeutic targets. The authors aimed to produce a comprehensive inventory of gene expression programmes expressed in primary GCs, and to identify those expression programmes significantly associated with patient survival. Design Using a network-modelling approach, the authors performed a large-scale meta-analysis of GC transcriptome data integrating 940 gastric transcriptomes from multiple independent patient cohorts. The authors analysed a training set of 428 GCs and 163 non-malignant gastric samples, and a validation set of 288 GCs and 61 non-malignant gastric samples. Results The authors identified 178 gene expression programmes (‘modules’) expressed in primary GCs, which were associated with distinct biological processes, chromosomal location patterns, cis-regulatory motifs and clinicopathological parameters. Expression of a transforming growth factor β (TGF-β) signalling associated ‘super-module’ of stroma-related genes consistently predicted patient survival in multiple GC validation cohorts. The proportion of intra-tumoural stroma, quantified by morphometry in tissue sections from gastrectomy specimens, was also significantly associated with stromal super-module expression and GC patient survival. Conclusion Stromal gene expression predicts GC patient survival in multiple independent cohorts, and may be closely related to the intra-tumoural stroma proportion, a specific morphological GC phenotype. These findings suggest that therapeutic approaches targeting the GC stroma may merit evaluation.