Abstract
The Phosphatidylinositol glycan class A (PIG-A) gene mutation assay phenotypically measures erythrocyte mutations, assessed here for their correlation to neoplastic progression in the gastro-oesophageal reflux disease (GORD)-Barrett’s metaplasia (BM)-oesophageal adenocarcinoma (OAC) model. Endoscopy patients underwent venipuncture and erythrocytes fluorescently stained for glycosyl phosphatidylinositol (GPI)–anchored proteins; CD55 and CD59. Using flow cytometry, GPI–anchor negative erythrocytes (mutants) were scored and compared amongst groups. The study enlisted 200 patients and 137 healthy volunteers. OAC patients had a three–fold increase in erythrocyte mutant frequency (EMF) compared to GORD patients (p < 0.001) and healthy volunteers (p < 0.001). In OAC patients, higher EMF was associated with worsening tumour staging (p = 0.014), nodal involvement (p = 0.019) and metastatic disease (p = 0.008). Chemotherapy patients demonstrated EMF’s over 19–times higher than GORD patients. Patients were further classified into groups containing those with non-neoplastic disease and those with high-grade dysplasia/cancer with 72.1% of cases correctly classified by high EMF. Within the non-neoplastic group, aspirin users had lower EMF (p = 0.001) and there was a positive correlation between body mass index (p = 0.03) and age (p < 0.001) and EMF. Smokers had EMF’s over double that of non-smokers (p = 0.011). Results suggest this test could help detect OAC and may be a useful predictor of disease progression.
Highlights
The Phosphatidylinositol glycan class A (PIG-A) gene mutation assay phenotypically measures erythrocyte mutations, assessed here for their correlation to neoplastic progression in the gastrooesophageal reflux disease (GORD)-Barrett’s metaplasia (BM)-oesophageal adenocarcinoma (OAC) model
Patients were further classified into groups containing those with non-neoplastic disease and those with high-grade dysplasia/cancer with 72.1% of cases correctly classified by high erythrocyte mutant frequency (EMF)
In the light of continued interest in blood-based approaches for the detection of cancer, we have evaluated for the first time, the potential of EMF to be deployed as a biomarker for genomic instability and potential surrogate marker of cancer using the GORD-BM-OAC model
Summary
The Phosphatidylinositol glycan class A (PIG-A) gene mutation assay phenotypically measures erythrocyte mutations, assessed here for their correlation to neoplastic progression in the gastrooesophageal reflux disease (GORD)-Barrett’s metaplasia (BM)-oesophageal adenocarcinoma (OAC) model. OAC patients had a three–fold increase in erythrocyte mutant frequency (EMF) compared to GORD patients (p < 0.001) and healthy volunteers (p < 0.001). Barrett’s oesophagus is a premalignant condition caused by the transformation of the normal squamous mucosa of the lower oesophagus to columnar-type mucosa This is caused by chronic exposure to refluxate constituents in patients with gastro-oesophageal reflux disease (GORD)[1]. Dysplasia has been the longstanding benchmark used in stratifying disease and assessing the risk of progression to cancer in Barrett’s patients[8] but requires expert gastrointestinal-pathology input and there is clear www.nature.com/scientificreports/. The recently developed Cytosponge has the potential to monitor OAC development through primary care on a large epidemiological scale[10], blood-based techniques have received attention in other cancer types
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