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

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.