POI-led oesophageal cancer study published in Neoplasia
22 May 2025
New research from (opens in a new window)Precision Oncology Ireland-funded researchers has highlighted important differences in the effect of saturated and unsaturated fats on different stages of disease progression in oesophageal adenocarcinoma.
Published online last week in Neoplasia, the study entitled “(opens in a new window)Saturated fat exacerbates mitochondrial dysfunction through remodelling of ATP production and inflammation in Barrett’s oesophagus compared to monounsaturated fat, particularly in contrast to oesophageal adenocarcinoma,” was led by POI-funded researchers Dr. Kathleen Mitchelson, Prof. Helen Roche and Prof. Jacintha O’Sullivan.
The study’s authors cultured two different cell lines representing oesophageal carcinoma and Barrett’s oesophagus (a non-cancerous precursor) with saturated and unsaturated fats. Saturated fats were found to induce an inflammatory response, especially in Barrett’s cells, suggesting that high intake of these fats could increase the likelihood of a patient with Barrett’s oesophagus progressing to a cancer diagnosis.
With obesity now overtaking smoking as the leading cause of cancer, gaining a deeper understanding of the precise relationship between diet and cancer development is crucial.
“Excess dietary energy leads to obesity, which is linked to some cancers”, said senior author (opens in a new window)Prof. Helen Roche. “But not all fats are the same. Here we show saturates alter fatty acid metabolism, oncogenic signalling, mitochondrial protein-protein networks coincident with greater inflammation in the early pre-cancer state. In contrast unsaturated fatty acids are less problematic.”
This study represents a great example of the collaborative network grown through POI, with 2 POI-funded PIs working together, while also drawing on the POI Shared Resources Platform to access proteomics expertise within Systems Biology Ireland and UCD Conway Institute.
First author Dr. Kathleen Mitchelson said, “We wanted to extend previous research within the Nutrigenomics group led by Prof. Helen Roche into obesity-linked cancers to understand how saturated versus unsaturated fatty acids may differ in their contribution to oesophageal disease progression.
“From the beginning of my PhD, Prof. Jacintha O’Sullivan was a co-mentor who provided invaluable expertise in translation oncology that allowed this project to grow. We were able to gain preliminary immunometabolic phenotyping on the different stages within oesophageal disease but warranted further exploration to fully elucidate specific mechanisms. We were able to utilise the expertise of Dr. David Gomez Matallanas and the shared resources available through POI to investigate changes in the proteome and signaling pathways which really increased the novelty and impact of this study.
“As an early career researcher, the ability to have access to the expertise and mentorship from three principal investigators was invaluable to my personal development. I was able to gain expertise in multiple areas which I have brought into my role as a postdoctoral research fellow,” Mitchelson concluded.
The collaboration has proved mutually beneficial, opening new avenues of research beyond the Roche and O’Sullivan groups. Dr. David Gomez Mattallanas, Investigator in Systems Biology Ireland and author on the study said, “the invitation from Prof. Roche to participate in this project led us to apply the methods that we have developed in SBI to identify the protein content of cells using mass spectrometry, allowing us to better understand the effect of diet on cancer. This was a new area of research for our group, and the collaboration quickly expanded to research other aspects of not only oesophageal but also colorectal cancer. Importantly, as part of her PhD, Kathleen Mitchelson worked closely with Kieran Wynne (CMAP Infrastructure Manager) to apply and develop new methods that are the foundations for new collaborations between the O'Sullivan and Roche groups and several researchers in SBI.”
Prof. Walter Kolch, Director of SBI and the POI research programme, emphasised the significance of the national collaboration aspect of this study.
"We're delighted to see this important collaborative publication coming from labs in two different universities in the Precision Oncology Ireland consortium," Kolch said. "Studies such as these resulting in key advances in personalised healthcare really show the success of the POI programme and the way in which it brings together our network of researchers with diverse expertise to answer some of the biggest challenges in modern medicine."