Study makes breakthrough with early marker for stomach cancer | MEDICUS 2024 Issue 1

Study makes breakthrough with early marker for stomach cancer
By Dr Chua Li Min, Science writer

(L-R): Prof Jimmy So, Dr Roxanne Chong, Dr Huang Kie Kyon, Prof Patrick Tan and Prof Yeoh Khay Guan, members of the study team, pose for a photo together // Credit: Alice Chia, Duke-NUS

In a major breakthrough, a team of researchers from Asia have uncovered a panel of genes that could improve screening and monitoring of patients at high-risk of developing stomach cancer.

By studying more than 1,100 tissue samples from individuals with intestinal metaplasia, a pre-malignant condition affecting the lining of the stomach, the multi-institutional team has identified 26 “driver genes” that play a pivotal role in a cell’s transition to stomach cancer, which is the third most common type of cancer in the region.

The findings were published in Cancer Cell and featured on the journal cover.

“By combining both clinical information and genetic data from advanced molecular technologies, we can better predict which stomach conditions might turn into stomach cancer compared to only using clinical information.”
Prof Patrick Tan

“The comprehensive dataset we’ve assembled provides unprecedented insights into the progression of cell changes in the stomach to cancer,” said Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, who collaborated on the research with clinicians and scientists from the Singapore Gastric Cancer Consortium and Seoul National University Hospital. The Singapore Gastric Cancer Consortium includes researchers from the National University Hospital and National University of Singapore’s Yong Loo Lin School of Medicine among others.

Characterised by changes in the cells lining the stomach, intestinal metaplasia is a well-known risk factor for stomach cancer. Patients afflicted with this condition face a sixfold increased risk of developing stomach cancer, which is often detected only at an advanced stage.

To trace the changes leading up to stomach cancer at the cellular level, patient samples from the Gastric Cancer Epidemiology Programme, a longitudinal cohort study comprising 2,980 Chinese participants aged 50 years or older were analysed.

“By combining both clinical information and genetic data from advanced molecular technologies, we can better predict which stomach conditions might turn into stomach cancer compared to only using clinical information,” explained Tan, who is also a professor with Duke-NUS’ Cancer & Stem Cell Biology Programme.

That has led to the team’s discovery of diverse cell populations that were associated with changes in the stomach lining, “raising the possibility that some of these cells may subsequently transform into cancerous cells”, said Dr Huang Kie Kyon, a senior research fellow with the Programme, who is a co-first author of the study.

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By analysing all the cells individually, the team were able to pinpoint a specific population of cells they believe are the “true culprits” behind stomach cancer, said Tan.

Likening their approach to zooming in on a pizza topping to measure its nutritional content, he added: “Looking at the data of each single ingredient, we will be able to dissect the specific contributions of each ingredient.”

This was in contrast to other techniques where, going by the same analogy, the entire pizza would have to be mashed just to study its nutritional content, said Tan: “This particular work allows us to see the small populations (of cells) we would otherwise miss when we grind everything up.”

Besides focusing on gene expression profiles within individual cells, the researchers also studied the genetic activity in different regions of the stomach lining across various timepoints to understand how cells go rogue in stomach cancer.

These findings offer a range of avenues for early intervention in the clinic said co-senior author Professor Jimmy So, who heads the Division of General Surgery at the National University Hospital: “We can now explore more targeted surveillance for patients at highest risk, as well as anti-inflammatorial or antibiotic agents to intercept pre-malignant clones before they evolve into cancer, potentially leading to improved patient outcomes through early detection.”

This could be implemented through a simple and inexpensive blood test to identify people who are at a very high risk of getting stomach cancer.

So’s colleague and Singapore Gastric Cancer Consortium lead Professor Yeoh Khay Guan, who is a senior consultant with the Division of Gastroenterology & Hepatology, added, “With this approach, we can divide people into groups based on their risk using either regular check-ups or these affordable blood tests. This helps to save resources by making sure those at the highest risk get the right tests and care they need.”