Gastric adenocarcinoma is a major cause of global cancer mortality.
Identifying molecular programmes contributing to gastric cancer patient survival may improve our understanding of gastric cancer pathogenesis, highlight new prognostic factors and reveal novel therapeutic targets.
Dr Yonghui Wu and colleagues from Singapore produced a comprehensive inventory of gene expression programs expressed in primary gastric cancers, and identified those expression programmes significantly associated with patient survival.
Using a network-modelling approach, the researchers performed a large-scale meta-analysis of gastric cancer transcriptome data integrating 940 gastric transcriptomes from multiple independent patient cohorts.
|TGF β signalling associated ‘super-module’ of stroma-related genes predicted patient survival |
The research team analyzed a training set of 428 gastric cancers, and 163 non-malignant gastric samples, and a validation set of 288 gastric cancers, and 61 non-malignant gastric samples
The team identified 178 gene expression programs expressed in primary gastric cancers, which were associated with distinct biological processes, chromosomal location patterns, cis-regulatory motifs and clinicopathological parameters.
The doctors noted that the expression of a transforming growth factor (TGF) β signalling associated ‘super-module’ of stroma-related genes consistently predicted patient survival in multiple gastric cancer validation cohorts.
The proportion of intra-tumoral stroma, quantified by morphometry in tissue sections from gastrectomy specimens, was also significantly associated with stromal super-module expression and gastric cancer patient survival.
Dr Wu's team commented, "Stromal gene expression predicts gastric cancer patient survival in multiple independent cohorts, and may be closely related to the intra-tumoral stroma proportion, a specific morphological gastric cancer phenotype."
"These findings suggest that therapeutic approaches targeting the gastric cancer stroma may merit evaluation."