In brief

A new comprehensive single-cell atlas of gastric cancers reveals rare cell types and a wide diversity thereof between tumours.

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Expanding the tumour cell catalogue

16 Sep 2022

New gastric cancer insights come to light with the help of powerful single-cell technologies.

You’ve heard the saying: no two snowflakes are identical. Likewise, cancer cells can display almost unfathomable diversity between patients. Even cells within a single tumour vary considerably, shaped by biochemical factors in the tumour microenvironment. This is especially true for gastric cancer, which makes it a particularly difficult condition to treat.

“Unfortunately, while gastric cancer is common in Asia and remains a significant cause of cancer death in Singapore, relatively little is known about the driving pathways underpinning this cancer type,” said Patrick Tan, Executive Director at A*STAR’s Genome Institute of Singapore (GIS).

Tan and his colleagues are part of the Singapore Gastric Cancer Consortium, an initiative focused on developing better and more targeted clinical strategies to help patients. Along with scientists from A*STAR’s Institute of Molecular and Cell Biology (IMCB) and Singapore Immunology Network (SIgN), Duke-NUS Medical School, National University Health System, Cancer Science Institute of Singapore and Japan’s Kumamoto University, the researchers came together to build a detailed atlas of the gastric tumour ecosystem, one cell at a time.

The researchers first started with a library of 48 tumour samples from 31 gastric cancer patients at different stages of the disease. They analysed more than 200,000 single cells individually, tracking mRNA levels to identify which genes were turned on or off in each cell.

A closer look at the data revealed that the cancer cells profiled fell into 34 different distinct categories based on their gene expression patterns. This included some never-before-seen rare cell populations, which were likely missed in prior studies that relied on smaller sample sizes.

These findings reinforce the urgent need for more personalized treatment programs for gastric cancer patients, said Tan. “Individual patient tumours each exhibited a unique pattern of these cell types, showing that relying on a one-size-fits-all approach to gastric cancer treatment is unlikely to prove fruitful.”

The team’s high-resolution peek into a previously hidden world of gastric tumours also revealed other valuable insights: immune cell and fibroblast populations also contributed to the growth and survival of gastric tumours.

“These pathways, rather than the cancer cells themselves, may represent new avenues for developing therapies,” Tan commented, adding that the team’s efforts serve as a much-needed resource in the field of gastric cancer research.

With one piece of the puzzle now in place, Tan said the team plans to add another dimension to the study by investigating how the tumour microenvironment changes over time. They are also leveraging the power of these single-cell technologies to uncover new diagnostic and therapeutic targets for other cancer types.

The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore (GIS), Institute of Molecular and Cell Biology (IMCB) and Singapore Immunology Network (SIgN).

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Kumar, V., Ramnarayanan, K., Sundar, R., Padmanabhan, N., Srivastava, S., et al. Single-cell atlas of lineage states, tumor microenvironment and subtype-specific expression programs in gastric cancer. Cancer Discovery 12, 670–691 (2022). | article

About the Researcher

Patrick Tan is the Executive Director of the Genome Institute of Singapore and a Professor at the Duke‐NUS Medical School. He is also Executive Director of Precision Health Research Singapore (PRECISE). Tan has won numerous accolades for his research, including the Young Scientist Award (A‐STAR), Singapore Youth Award, SingHealth Investigator Excellence Award, Chen New Investigator Award (Human Genome Organization), President’s Science Award, and the Japanese Cancer Association International Award. In 2018, he received the American Association for Cancer Research (AACR) Team Science Award as Team Leader, representing the first time a team from Asia has received the award. He is an elected member of the American Society for Clinical Investigation (ASCI), the Bioethics Advisory Committee (BAC), and a Board Member of the International Gastric Cancer Association.

This article was made for A*STAR Research by Wildtype Media Group