Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS

ABSTRACT: Oesophageal adenocarcinoma (OAC) is an aggressive cancer with a five-year survival of <15%, and the incidence is predicted to double within the next 20 years. Current neo-adjuvant chemotherapy treatment strategies only benefit a minority (20-30%) of patients and there are currently no methods available to differentiate between responders and non-responders. Here we performed quantitative proteomics using Sequential Window Acquisition of all THeoretical fragment-ion spectra-Mass Spectrometry (SWATH-MS) on albumin/IgG-depleted and non-depleted plasma samples from 23 patients with locally advanced OAC or oesophageal gastric junction cancers prior to treatment. Individuals were grouped based on tumour regression (TRG) score (TRG1-3 vs TRG4 and 5) after chemotherapy and differentially abundant proteins were compared using univariate and multivariate analyses. Protein depletion led to the identification of around twice as many proteins in the samples compared to non-depletion. SWATH-MS revealed significant quantitative differences in the abundance of several proteins (p<0.05) between the two groups. These included all three c1q subunit proteins, C1QA, C1QB and C1QC, which were of higher abundance in the low TRG group (higher degree of regression in response to treatment). Of those that were found to be of higher abundance in the high TRG group, GSTP1 was found to exhibit the lowest p-value (univariate analysis) and highest accuracy and Cohen’s kappa value (multivariate analysis). The concentrations of c1q complex and GSTP1 were further examined and validated using ELISA-based assays. This study provides quantitative information relating to differences in the plasma proteome that underpin response to chemotherapeutic treatment in oesophageal cancers.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Adenocarcinoma

SUBMITTER: Sally Shirran  

LAB HEAD: Swati Arya

PROVIDER: PXD032137 | Pride | 2022-08-22

REPOSITORIES: Pride