by ecancer reporter Janet Fricker

Four subgroups for gastric cancer (GC) with different molecular alterations and outcomes for survival have been defined in a study by the Asian Cancer Research Group.

In Nature Medicine, the group describe how they have provided a ‘consistent and unified framework’ for further clinical and pre-clinical translational research.

In GC one of the main reasons for observed heterogeneity in response to treatments has been a one-size-fits-all approach taken to treatment, with little attention paid to the underlying molecular mechanisms driving differences in cancer aggressiveness and treatment outcomes.

In the current study, the Asian Cancer Research Group set out to establish clinically molecular subtypes for GC that would encompass heterogeneity and provide useful clinical information.

The investigators undertook whole genome sequencing of 300 primary tumours, of which 49 had appeared in a previous study.

The team looked for pre-defined sets of gene expression signatures including epithelial-to-mesenchymal transition (EMT), microsatellite instability (MSI), and TP53 activity.

Once they had identified four subgroups - MSI (n=68), MSS /TP53 (n=79), MSS/TP53 - (n=107), and MSS/EMT subtype (n=46), they analysed survival and patterns of recurrence for each.

The results showed that the MSI subtype had the best prognosis, followed by the MSS/TP53 and MSS/TP53-, with the MSS/EMT subtype showing the worst prognosis.

Additionally, the results showed that the MSS/EMT group had a 63% chance of recurrence compared 44% for the MSS/TP53- group, 37% for the MSS/TP53 group, and 22% for the MSI group.

“Our study has potentially important clinical implications in GC. First, molecular screening and therapeutic development according to the GC molecular classification should be considered, especially when newer targeted agents are being developed,” write the authors.

In practice, however, cost is one of the foreseeable hurdles for the use of molecular signatures.

“We believe that multiplexed assays such as Mammaprint or PAM50 can be developed and applied in GC,” write the authors.

Reference

R Cristescu, J Lee, M Nebozhyn, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nature Medicine.