Data Independent Acquisition of plasma biomarkers of response to Neoadjuvant Chemotherapy in Pancreatic Ductal Adenocarcinoma

ABSTRACT: The detection of disease-related plasma biomarkers has challenged the proteomic community for years. On the one hand there are many attractive features including the ease of collection and small volume needed for analysis, but on the other hand, the presence of high abundance proteins complicates technical sample preparation procedures and reduces proteome dynamic range. Data independent acquisition label free quantitation (DIA-LFQ) by mass spectrometry is an approach that partly overcomes the dynamic range issue; however, generating the peptide spectral reference libraries that allow extensive analysis of the plasma proteome can be a slow and expensive task which is unattainable for many laboratories. We investigated the re-purposing of publically available plasma proteome datasets and the impact on peptide/protein detection for DIA-LFQ. We carried out these studies in the context of pancreatic ductal adenocarcinoma, seeking biomarkers of response to neoadjuvant chemotherapy. We demonstrated the benefit in searching DIA data against multiple spectral libraries to show that complement activation was linked to response in these patients, confirming previous observations derived from proteomic analyses of PDAC tumours. Our workflow demonstrates that DIA-LFQ can be readily applied in the oncology setting for the putative assignment of clinically relevant plasma biomarkers.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Matthew O'Rourke  

LAB HEAD: Mark Molloy

PROVIDER: PXD020694 | Pride | 2022-03-02

REPOSITORIES: Pride