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Proteomic profiling reveals potential plasmatic biomarkers for pancreatic adenocarcinoma in Brazilian patients

ABSTRACT: Pancreatic cancer is one of the most lethal cancer types worldwide, with the majority of the diagnostics being pancreatic adenocarcinomas (PDAC). Early and accurate diagnosis are among the best alternatives to improve treatment effectiveness and survival of PDCA patients; however, plasmatic biomarkers molecules are scarce. Here, we describe a proteomic screening on depleted plasma from 29 PDAC patients and 30 healthy controls, aiming to identify potential biomarkers for PDAC diagnosis. We observed 121 differentially expressed proteins (DEPs), which were associated with the tumor biology and clinical behavior. We emphasize the potential of three over-expressed proteins (ORM1, ORM2, and SERPINA1), and four down-expressed proteins (ALDOA, PPIA, VCL, and SPARC) as biomarkers in PDAC, which were also correlated with disease staging. It was also demonstrated that some proteins could be used as complementary biomarkers associated with gold-standard CA19-9. Our high throughput proteomics approach suggests a set of proteins with potential use in PDAC diagnosis, giving light to future validation and application in clinical practice, enabling target proteomics and other serological assays.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Pancreas Adenocarcinoma

SUBMITTER: Michel Batista

LAB HEAD: Mateus Nóbrega Aoki

PROVIDER: PXD064439 | Pride | 2025-10-24

REPOSITORIES: Pride

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			Action	DRS
	20230704_128723_Mateus_PLASMAPOOL1_1.raw	Raw
	20230704_128723_Mateus_PLASMAPOOL1_2.raw	Raw
	20230704_128823_Mateus_PLASMAPOOL2_1.raw	Raw
	20230704_128823_Mateus_PLASMAPOOL2_2.raw	Raw
	20230704_128923_Mateus_PLASMAPOOL3_1.raw	Raw

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Project description:Pancreatic ductal adenocarcinoma (PDAC) suffers from lack of an effective diagnostic method, limiting improvement in patient survival. Although the FDA-approved biomarker CA19-9 has been used for detection and surveillance of PDAC, its clinical utility is generally regarded to be limited due to its suboptimal diagnostic performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics, and identified a plethora of protein biomarker candidates for PDAC. Yet few if any has successfully transitioned into clinical practice. This translational standstill is owed partly to the limited considerations of practical needs and perspectives of clinical implementation in the course of a biomarker pipeline, such as demonstrating analytical validity of proposed biomarkers, which is critical to turning research-grade assays to clinical-grade tests. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS method. In the discovery phase, we systematically collected putative biomarkers from both in-house proteomics data and the large volume of literature documenting PDAC biomarkers. In the verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation criteria. Given the intended use of our panel (i.e., primary screening), we adopted a high-throughput protocol including short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). To further facilitate clinical implementation, we performed verification of our panel on serum samples, which are usually the preferred biospecimen available in clinical settings. We developed a stacking ensemble model based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone (AUC 0.919 and 0.830, respectively). A large-scale clinical validation study is underway to demonstrate the clinical validity of our panel.

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Proteomic profiling reveals potential plasmatic biomarkers for pancreatic adenocarcinoma in Brazilian patients

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