Scientists in Singapore have assembled a large, high-resolution atlas of gastric cancer, a leading cause of global cancer death. The atlas provides, at the level of single cells, new insights into how gastric cancers progress and how tumours from separate patients differ from one another. The findings also identified molecular pathways driving gastric cancer growth and spread to other organs, and also how the disease can be better treated.
The research was led by Duke-NUS Medical School and the Agency for Science, Technology and Research (A*STAR)’s Genome Institute of Singapore (GIS), and involving collaborators from the National University Health System (NUHS), A*STAR’s Singapore Immunology Network (SIgN) and Institute of Molecular and Cell Biology (IMCB), the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS), and Kumamoto University, Japan.
“Patients with gastric cancer—also referred to as stomach cancer—are notoriously difficult to treat because we lack a clear understanding of the types of cells that make up their tumours,” said the study’s principal investigator, Professor Patrick Tan, from Duke-NUS’ Cancer & Stem Cell Biology Programme and GIS and also a Senior Principal Investigator at CSI Singapore. “With precision oncology, cutting-edge technologies like single-cell sequencing can analyse patient cancers at unprecedented depth and resolution, to tailor therapies for patients and reveal new pathways to improve diagnoses and treatments.”
This work was performed as part of the Singapore Gastric Cancer Consortium (SGCC), a national body of clinicians and scientists working in translational research on gastric cancer supported by the National Medical Research Council. The research team sampled 46 tumours from 31 patients at various stages of the disease. From these samples, they analysed 200,000 separate cells, using innovative techniques to assess individual patterns of gene expression.
The scientists found more than 30 different cell types, some of which had not been detected in gastric tumours before. Tumours from different patients showed a different composition of these cells, which helps to explain why similar treatments can have very different outcomes.
Some types of gastric tumour were found to contain immune cells, particularly B cells that control the generation of antibodies. This suggests that cancer immunotherapy, a type of treatment that uses a person’s own immune system to fight cancer, could be applied to the disease. The study also showed a previously unknown role for common cells called fibroblasts in driving gastric cancer. Targeting these cells could offer new avenues for treatment.
Dr Shyam Prabhakar, Associate Director, Spatial and Single Cell Systems, GIS, said: “This work puts the power of single-cell sequencing to very effective use by creating the first in-depth map of cell types in stomach cancer. Now that we have the ‘parts list’, we can identify the vulnerabilities of these tumours and start to target them.”
Building on this work, the research team is currently investigating how the cell populations identified in the study change over time, either during early cancer development or as a consequence of drug treatment. This information may yield pathways that can be exploited for early cancer detection and drug development.
Furthermore, because many of the features identified in this study may be applicable to other cancer types, the team will collaborate with researchers working on other cancers to pool data and identify cell populations that contribute to multiple cancers.