Behind the Paper
The Silent Killer
Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), is among the most aggressive malignancies. The five-year survival rate remains around 13%, and the majority of patients are diagnosed at a late stage because the disease is asymptomatic or presents with vague symptoms [1]. Yet when detected early, the chances of long-term survival increase dramatically. Prospective surveillance of high-risk individuals shows that early detection can extend median overall survival from approximately 1.5 years to nearly 10 years [2]. The key challenge is how to diagnose the disease at an early stage. Population-wide screening is not recommended by medical societies; instead, targeted screening programs for individuals at high risk of developing PDAC are recommended [3]. However, there is currently no worldwide blood-based biomarker capable of reliably detecting pancreatic cancer at early stages.
Why We Turned to Lipids
The current diagnosis of early-stage pancreatic cancer relies primarily on imaging modalities such as endoscopic ultrasonography and magnetic resonance imaging. Although they are effective and accurate, these approaches are costly, low-throughput, time-consuming, and uncomfortable or invasive for patients. The only globally used routine blood biomarker, CA 19-9, has limited sensitivity in early stages and performs poorly in individuals with low antigen secretion. In our previous research, we demonstrated that lipidomic analysis, the comprehensive quantitative analysis of lipids, can detect systematic alterations in lipid concentrations in human blood [4,5]. This methodology has been protected by patents in Europe [6], the United States [7], Japan [8], and the Republic of Singapore [9]. Building on these findings, our objective was to determine whether these lipidomic alterations could serve as a noninvasive screening tool for the early detection of PDAC.
From the Laboratory to Clinical Practice
Before moving toward clinical validation, we needed to address several critical questions that arose from our previous work.
- Is the lipidomic profile influenced by gender? Should the results be interpreted in gender-specific models?
- Is plasma or serum the more appropriate matrix? Could blood processing affect the analytical outcome?
- Does the method remain robust in individuals at high risk of developing PDAC? Is the lipid profile of high-risk individuals closer to healthy controls or to PDAC patients?
- Does the method achieve performance comparable to established imaging modalities?
To systematically address these questions, the study was designed in two phases (Figure 1). In Phase 1, we refined the methodology and addressed the questions that arose from the earlier studies. In Phase 2, we applied the method to samples from HRI and compared the results with current blood biomarkers and imaging methods.
Figure 1: Overview of the study design including methodology, research questions, and sample numbers (n) for individual cohorts.
Pilot study
A total of 488 individuals were prospectively enrolled in the study, including 177 patients with PDAC, 218 healthy controls, and 93 high-risk individuals for developing pancreatic cancer. Samples were prospectively collected in collaboration with Palacký University Olomouc and University Hospital, Charles University, and two national pilot studies in the Czech Republic, SCREPAN and HEPACAS, both focused on the early detection of PDAC through regular imaging surveillance. The performance of the lipidomic test exceeded our expectations (Figure 2).
- The lipidomic test distinguishes PDAC patients from healthy controls with an accuracy exceeding 95%, including robust detection of early-stage cases and even individuals with low CA 19-9 secretion.
- The sensitivity is approximately 30% higher than that of CA 19-9.
- In high-risk individuals, the method achieves a specificity of over 96%, comparable to established imaging-based approaches.
Figure 2: Results of the lipidomic profiling of PDAC patients (T) and healthy controls (N) using plasma models. A) Comparison of lipid profiles using supervised OPLS-DA score plots. B) Sensitivity of individual methods according to tumor stages for the lipidomic profiling method (Lipids), CA 19-9, and CEA. Coloring according to tumor stage: T1 – yellow, T2 – orange, T3 – red, T4 – rose, and Tx – brown, where information about the stage is not available.
Perspectives
The results demonstrate that the lipidomic approach fulfills the key requirements of a screening tool, it is noninvasive, cost-effective, high-throughput, and sufficiently accurate even in early-stage disease. However, this remains a pilot study with a limited number of samples, and clinical validation is essential. A multicenter clinical trial is currently underway (ClinicalTrials.gov: NCT6549725), realized by Lipidica (https://www.lipidica.com/), which is a spin-off company of the University of Pardubice and FONS JK Group. Sixteen clinical centers across the Czech Republic are participating in the study, which aims to validate the method in a large cohort of high-risk individuals and patients with resectable PDAC tumors, directly comparing it to imaging modalities.
At the same time, research continues at the University of Pardubice within the framework of the ERC Advanced Grant project “Oncolipidomics: Why is lipidomic dysregulation pattern in blood similar for various cancers?”. This work focuses on clarifying the biological mechanisms underlying cancer-associated alterations in blood lipid profiles. We kindly welcome talented PhD students and early-career postdoctoral researchers interested in lipidomic, metabolomic, and glycomic analysis using mass spectrometry to join our team.
Link to the paper:
https://doi.org/10.1038/s43856-026-01445-5
References
[1] Yang, J.S., et al. Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review. Cancer Commun. 41, 1257-1274 (2021).
[2] Canto, M.I., et al. Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance. Gastroenterology 155, 740-751 (2018).
[3] Mazer, B.L., et al. Screening for pancreatic cancer has the potential to save lives, but is it practical? Expert Rev. Gastroent. 17, 555-574 (2023).
[4] Wolrab, D., et al. Lipidomic profiling of human serum enables detection of pancreatic cancer. Nat. Commun. 13, 124 (2022).
[5] Peterka, O., et al. HILIC/MS quantitation of low-abundant phospholipids and sphingolipids in human plasma and serum: Dysregulation in pancreatic cancer. Anal. Chim. Acta 1288, 342144 (2024).
[6] Holčapek, et al. A method of diagnosing pancreatic cancer based on lipidomic analysis of a body fluid. European Patent EP 3514545 B1. Granted 7 October 2020.
[7] Holčapek, et al. How to diagnose cancer based on lipidomics analysis of body fluids. Japan Patent JP 7086417. Granted 10 June 2022.
[8] Holčapek, M., et al. A method of diagnosing cancer based on lipidomic analysis of a body fluid. Singapore Patent SG 11202006667V. Granted 24 January 2024.
[9] Holčapek, et al. Method of diagnosing cancer based on lipidomic analysis of a body fluid. US Patent US 12,247,981 B2. Granted 11 March 2025.