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Scientists make important oesophageal cancer cells discovery

Friday August 13th 2021

Abnormal cells that develop into oesophageal cancer start life as cells of the stomach, British researchers reported last night.

A study by scientists at the University of Cambridge found that an oesophageal adenocarcinoma is always preceded by Barrett’s oesophagus, even if these cells are no longer visible at the time of cancer diagnosis.

This, they write in the latest edition of Science, confirms that screening for Barrett’s is an important approach to oesophageal cancer control.

Although it has been known for some time that the development of this cancer is linked with Barrett’s oesophagus, which shows up in endoscopy as a pink ‘patch’ in the surface of the oesophagus, the question of where these abnormal cells come from has remained a mystery.

Now, a multidisciplinary group of scientists led by Professor Rebecca Fitzgerald at the Medical Research Council Cancer Unit, University of Cambridge, provides the most comprehensive explanation to date.

Joint first author Dr Lizhe Zhuang, said: “It’s intriguing that, although Barrett’s oesophagus predominately occurs in the lower part of oesophagus close to stomach, it has so-called ‘goblet cells’ resembling a much more distant organ, the small intestine.

“Over the past 20 years there have been at least six different hypotheses about the origin of Barrett’s oesophagus. Using the latest techniques, we believe we have arrived at an answer to this mystery.”

The research team analysed tissue samples from patients with Barrett’s oesophagus and from organ donors who have had the condition.

Dr Zhuang and colleague Dr Karol Nowicki-Osuch established a detailed atlas of human cells and tissues from all possible origins of Barrett’s oesophagus, including oesophageal submucosal glands.

The researchers then used molecular technologies, including single cell RNA sequencing, to compare the maps of cells from healthy tissues, Barrett’s oesophagus and oesophageal adenocarcinoma.

They also looked at methylation profiles and at genetic linage to trace back where a particular cell type originated.

The results showed a strong similarity between stomach cells and Barrett’s oesophagus, which suggested the cells at the very top of the stomach can be reprogrammed to adopt a new tissue identity, becoming more like intestine cells, and replace the oesophageal cells.

The team went on to show that two genes, MYC and HNF4A, are the keys that switch the tissue identity from stomach to intestinal cells.

Dr Nowicki-Osuch said: “The techniques we used have shown us the internal processes that happen in the stomach cells when they become Barrett’s. The big question now is: what triggers these genes? It’s likely to be a complex combination of factors that include bile acid reflux (often felt as heartburn) and other risk factors, such as obesity, age, male sex and Caucasian ethnicity.”

Importantly, the researchers found that all oesophageal adenocarcinoma cells begin as stomach cells before transforming into Barrett’s cells and then into cancer cells.

Prof Fitzgerald added: “Even if the pre-cancerous Barrett’s is not visible at the time of cancer diagnosis, our data suggests the cancer cells will have been through this stage. This has been debated for some time, but our conclusion is important as it means that screening for Barrett’s is an important approach to controlling oesophageal cancer.”

Nowicki-Osuch K, Zhuang L et al. Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition. Science 12 August 2021

[abstract]

Tags: Cancer | Gastroenterology | UK News

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