Good news! Cancer is history (soon)!
"The findings, ... could help improve screening for and early detection of oesophageal cancer, the sixth most deadly cancer, helping improve outcomes for the disease.
Cancer of the oesophagus, including its most common form oesophageal adenocarcinoma (OAC) ...
To answer the question of whether Barrett’s oesophagus is a pre-requisite for OAC, researchers ... analysed epidemiological and clinical data from 3,100 OAC patients undergoing surgery to remove their tumour or diseased tissue. Patients were recruited from 25 centres across the UK.
The team also analysed whole genome sequencing data from 710 patients, which allows them to look at all of an individual’s DNA, and whole exome sequencing from multiple samples taken from 87 patients, allowing them to understand how their tumours evolved and how different parts of the same cancer may differ genetically.
The researchers hypothesised that if OAC can arise through different routes – not always involving Barrett’s oesophagus – then genomic data and associated risk factors would differ between these two groups. Conversely, extensive overlap would strongly suggest that Barrett’s oesophagus plays a central role in OAC progression.
Just over a third of participants (35%) had a diagnosis of Barrett’s oesophagus. However, the DNA, mutations, genomic patterns, and cellular ‘identity’ inside the cancers were essentially indistinguishable, regardless of whether doctors could identify Barrett’s oesophagus during endoscopy or in pathology samples.
The only major difference between cancers with or without visible Barrett’s oesophagus was the tumour stage – those patients without signs of Barrett’s oesophagus tended to have more advanced cancers.
However, the team found biomarkers for Barrett’s oesophagus, such as the proteins TFF3 and REG4 present in the oesophagus cells at all disease stages including before the cancer has developed. This suggests that the growing tumour can destroy the original Barrett’s tissue, but importantly that proteins such as TFF3 and REG4 could be used to find individuals at future risk of oesophageal cancer. ..."
From the abstract:
"Cancer generally takes years to evolve, and early diagnosis can prevent life-threatening cancer. Establishing a link between precancerous states and cancer is essential for effective screening and prevention.
Esophageal adenocarcinoma (EAC) is an increasingly prevalent, poor-outcome cancer, and its presumed precursor, Barrett’s esophagus (BE), characterized by intestinal metaplasia, is evident in only about half of cases.
Here to test whether BE is a prerequisite to EAC, we integrated epidemiological and clinical characteristics in a prospective cohort of 3,100 patients with EAC for any evidence of BE (BE-positive and BE-negative) and compared genomic features using a subset of 710 patients with whole-genome sequencing and 87 patients (380 samples) with multiregional whole-exome sequencing. Demographic and genomic features typically associated with BE were observed across BE-positive and BE-negative EAC cases.
Notably, molecular features consistent with early BE evolution were detected in both phenotypes.
Advanced tumor stage was the only variable that corresponded with increased likelihood of BE-negative EAC, including in some patients with a previous BE diagnosis.
Phylogenetic analyses revealed shared evolutionary trajectories, and spatial transcriptomic and proteomic analyses demonstrated intestinal metaplasia-associated lineage markers in both groups.
These findings suggest a single pathway to EAC, with implications for early diagnosis and prevention strategies."
Fig. 1: The study design to establish whether there is a BE-independent pathway to EAC.
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