A multiplex proteomics analysis reveals a novel plasma biomarker signature that predicts for outcomes in gastro-oesophageal cancer


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Eilidh McCulloch1,Alan Bilsland1,Liz-Anne Lewsley2,Antonia MacMillan2,Martin MacLeod2,Jennifer Walker1,Jamie Stobo2,James Paul2,W. Nicol Keith1,Patricia Roxburgh1,Fiona Thomson1,T.R. Jeffry Evans1
1Glasgow ECMC, Institute of Cancer Science, University of Glasgow,2CRUK Clinical Trials Unit, Institute of Cancer Science, University of Glasgow

Abstract

Background

Patients with advanced gastro-oesophageal adenocarcinoma (GO) have a median overall survival (OS) of only approximately 10 months. We have previously reported that high pre-chemotherapy levels of IL6, IL8 and IL10 in plasma are associated with shorter progression-free (PFS) and OS. We have expanded these findings through multiplex analysis of 92 immuno-oncology-related protein markers, aiming to identify a circulating biomarker signature that can provide an early prediction of response to therapy and OS. This predicative biomarker signature may be useful for the development of novel therapeutic strategies for GO cancer. 

Method

Patients with advanced gastric or oesophageal adenocarcinoma were enrolled into a multi-centre, open, non-randomised study (‘UKCRN 12435- ‘RTL Advanced’ study). Plasma samples were collected prior to starting chemotherapy (ECX/ECF or EOX/ECF) and 92 immuno-oncology associated proteins were simultaneously measured using a proximity extension assay (Olink, Uppsala). Primary endpoint measures included OS and PFS.

Results

Of the 92 immuno-oncology markers analysed, 78 biomarkers were quantifiable in patient plasma, with the remaining 14 being below the limit of detection of the assay. For 182 patients (150 OS events), we confirmed that baseline levels of IL-6 and IL-8 were elevated in poor responders. Using Kaplan Meier survival analysis and adjusted p values (based on continuous variables using Cox regression), high levels of IL-6 and IL-8 have a significant association with shorter OS (p=0.00002, 0.00004 respectively) and PFS (p=0.018, 0.018 respectively), consistent with previous results.  In addition, high levels of angiopoietin 2, VEGF-A and CXCL10 have significant association with shorter OS (all 3 markers with p=0.026), but had no significant association with PFS.

Conclusion

High plasma levels of IL-6, IL-8, Angiopoietin2, VEGF-A and CXCL10 measured prior to chemotherapy treatment may be markers of worse OS, where high IL-6 and 8 may also be markers of shorter PFS.