Abstract
Simple SummaryDetecting cancer early significantly increases the chances of successful (surgical) treatment. Pancreatic cancer is one of the deadliest cancer forms, since it is usually discovered at a late and already spread stage. Finding biomarkers showing pancreatic cancer at an early stage is a possible approach to early detection and improved treatment. The aim of our study was to assess the potential of tissue polypeptide specific antigen (TPS) as a biomarker for early pancreatic cancer detection. We studied TPS levels in blood plasma samples from a population-based biobank in Västerbotten, Sweden that were collected before individuals were diagnosed with pancreatic cancer. Although TPS levels are raised at diagnosis, this occurs late, and thus TPS does not seem to hold promise as an early detection marker for pancreatic cancer.Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging, and late diagnosis partly explains the low 5-year survival. Novel and sensitive biomarkers are needed to enable early PDAC detection and improve patient outcomes. Tissue polypeptide specific antigen (TPS) has been studied as a biomarker in PDAC diagnostics, and it has previously been shown to reflect clinical status better than the ‘golden standard’ biomarker carbohydrate antigen 19-9 (CA 19-9) that is most widely used in the clinical setting. In this cross-sectional case-control study using pre-diagnostic plasma samples, we aim to evaluate the potential of TPS as a biomarker for early PDAC detection. Furthermore, in a subset of individuals with multiple samples available at different time points before diagnosis, a longitudinal analysis was used. We assessed plasma TPS levels using enzyme-linked immunosorbent assay (ELISA) in 267 pre-diagnostic PDAC plasma samples taken up to 18.8 years before clinical PDAC diagnosis and in 320 matched healthy controls. TPS levels were also assessed in 25 samples at PDAC diagnosis. Circulating TPS levels were low both in pre-diagnostic samples of future PDAC patients and in healthy controls, whereas TPS levels at PDAC diagnosis were significantly increased (odds ratio 1.03; 95% confidence interval: 1.01–1.05) in a logistic regression model adjusted for age. In conclusion, TPS levels increase late in PDAC progression and hold no potential as a biomarker for early detection.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type with a global overall 5-year survival of 9% [1]
Tissue polypeptide specific antigen (TPS) levels were increased at PDAC diagnosis, but this increase was not observed in pre-diagnostic PDAC samples
We investigated the potential of circulating TPS levels as an early detection biomarker using a pre-diagnostic PDAC cohort with samples collected 1.6 months–18.8 years prior to diagnosis
Summary
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type with a global overall 5-year survival of 9% [1]. Sensitive biomarkers for detecting PDAC at an earlier stage are needed to improve the prognosis. Such biomarkers would lead to more patients being diagnosed at stages amenable for curative surgery. Another study estimated that early- to late-stage PDAC progression takes only 1.3 years on average by comparing the mean age in relation to stage at diagnosis [4]. We previously found circulating TPS levels to be higher in PDAC patients compared to healthy controls [25]. TPS was elevated pre-operatively and suggested to hold greater potential than CA 19-9 for early diagnosis (stage I & II) of PDAC [24]. TPS levels were increased at PDAC diagnosis, but this increase was not observed in pre-diagnostic PDAC samples
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