A novel blood-based biomarker for OAC with the potential for use as an early treatment response predictor.


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Rachel Lawrence1,Lucy Swithenbank2,Hasan Haboubi2,Lisa Williams3,Sarah Gwynne3,Shareen Doak4,Gareth Jenkins2
1Swansea University Medical school,2Swansea University medical school,3ABMU NHS Trust,4Swnasea University medical school

Abstract

Background

Oesophageal adenocarcinoma (OAC) is the 13th most common cancer in the UK with 9 211 new cases diagnosed annually. Due to the late stage in which OAC is commonly diagnosed, treatment options are usually limited to chemo/radiotherapy with limited success, meaning the 5-year survival rate remains poor at 15%.

Here we describe a novel blood-based biomarker for OAC based on the PIG-A mutation assay, which has the further potential of predicting early treatment response. We hypothesise that cancer patients will have a higher level of this circulating mutation compared to controls. Furthermore, will patients undergoing chemo/radio therapy who display an increase in mutation frequency during their treatment respond better to such therapies?

Method

Blood samples were obtained from consenting patients attending endoscopy including patients with reflux disease, Barrett’s metaplasia (BM) and newly diagnosed OAC. Multiple blood samples were obtained from patients with OAC throughout their treatment course. Ten microliters of whole blood was stained with antibodies against the erythrocyte marker CD235a and two GPI-linked proteins (CD55 and CD59) and analysed using flow cytometry.

Results

With over 300 participants currently recruited to the study including healthy volunteers, data shows that treatment naïve OAC patients had a 3-fold increase in PIG-A mutant frequency compared to reflux patients (p<0.001). Reflux (n=75), Barrett’s (n=63) and treatment naïve cancer patients (n=38) had a median PIG-A mutant frequency of 3.2 (95% CI: 1.51-5.43), 4.52 (95% CI: 2.53-6.09) and 9.75 (95% CI: 3.76-17.52) respectively.

OAC patients undergoing treatment (n=13) had intra-individual variation of 1 to 8 fold increase in mutation frequency compared to their pre-treatment levels, with mutant frequencies in the range of 1.0-29.8 mutant RBC’s/million. Correlation with therapeutic response is on-going.

Conclusion

The PIG-A mutation assay has potential as a less-invasive biomarker for OAC as well as a treatment-response tool to identify patients with limited response to current therapies.