# Serum proteomics reveals survival-associated biomarkers in pancreatic cancer patients treated with chemoimmunotherapy

**Authors:** Marco Tognetti, Lopamudra Chatterjee, Nigel Beaton, Kamil Sklodowski, Roland Bruderer, Lukas Reiter, Christoph B. Messner

PMC · DOI: 10.1016/j.isci.2025.112230 · iScience · 2025-03-16

## TL;DR

Blood protein analysis identifies survival biomarkers in pancreatic cancer patients treated with chemoimmunotherapy.

## Contribution

Deep serum proteomics identifies survival-associated biomarkers and glycolytic enzyme links in PDAC patients treated with anti-PD-1 therapy.

## Key findings

- Glycolytic enzymes correlate with survival in anti-PD-1-treated PDAC patients.
- A set of serum protein biomarkers predicts one-year survival with high accuracy (AUC = 0.91).
- Serum proteomics reveals molecular subgroups of PDAC patients with prognostic value.

## Abstract

Immunotherapy has transformed the landscape of cancer treatment but remains largely ineffective for patients with pancreatic ductal adenocarcinoma (PDAC). Some patients, however, show improved outcomes when treated with a combination of immunotherapy and chemotherapy. Here, we conducted deep serum proteome analysis to investigate the protein profiles of PDAC patients and changes during this combinatorial treatment. Utilizing an advanced serum workflow, we quantified 1,011 proteins across 211 samples from 62 patients. Glycolytic enzymes were associated with survival in anti-PD-1-treated patients, with their abundances significantly correlating with expression levels in tumor biopsies. Notably, a set of protein biomarkers was found to be highly predictive of survival in anti-PD-1-treated patients (area under the curve [AUC] = 0.91). Overall, our data demonstrate the potential of deep serum proteomics for precision medicine, offering a powerful tool to guide patient selection for treatment through minimally invasive serum protein biomarker measurements.

•Serum proteomics reveals molecular subgroups of PDAC patients with prognostic value•Glycolysis is associated with survival in nivolumab-treated patients•Protein biomarkers predict one-year survival in patients receiving nivolumab treatment

Serum proteomics reveals molecular subgroups of PDAC patients with prognostic value

Glycolysis is associated with survival in nivolumab-treated patients

Protein biomarkers predict one-year survival in patients receiving nivolumab treatment

Treatment; Body substance sample; Cancer; Proteomics

## Linked entities

- **Diseases:** pancreatic ductal adenocarcinoma (MONDO:0005184)

## Full-text entities

- **Genes:** PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}
- **Diseases:** cancer (MESH:D009369), pancreatic cancer (MESH:D010190), PDAC (MESH:D021441)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11999289/full.md

## References

81 references — full list in the complete paper: https://tomesphere.com/paper/PMC11999289/full.md

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Source: https://tomesphere.com/paper/PMC11999289