A Blood-Based Multi Marker Assay Supports the Differential Diagnosis of Early-Stage Pancreatic Cancer

Abstract

The most frequent malignancy of the pancreas is the pancreatic ductal adenocarcinoma (PDAC). Despite many efforts PDAC has still a dismal prognosis. Biomarkers for early disease stage diagnosis as a prerequisite for a potentially curative treatment are still missing. Novel blood-based markers may help to overcome this limitation. Methods: Prior to surgery plasma levels of thrombospondin-2 (THBS2), which was recently published as a novel biomarker, and CA19-9 from 52 patients with histologically proven PDAC were determined, circulating cell-free (cfDNA) was quantified. 15 patients with side-branch IPMNs without worrisome features and 32 patients with chronic pancreatitis served for comparison. Logit (logistic regression) models were used to test the performance of single biomarkers and biomarker combinations. Results: CA19-9 and THBS2 alone showed comparable c-statistics of 0.80 and 0.73, respectively, improving to 0.87 when combining these two markers. The c-statistic was further increased to 0.94 when combining CA19-9 and THBS2 with cfDNA quantification. This marker combination performed best for all PDAC stages but also for PDACs grouped by stage. The greatest improvement over CA19-9 was seen in the group of stage I PDAC, from 0.69 to 0.90 for the three marker combination. Conclusion: These data establish the combination of CA19-9, THBS2 and cfDNA as a composite liquid biomarker for non-invasive diagnosis of early-stage PDAC.

Combined Expression of Plasma Thrombospondin-2 and CA19-9 for Diagnosis of Pancreatic Cancer and Distal Cholangiocarcinoma: A Proteome Approach

“…THBS2 expression has been described previously as biomarker for patients with PDAC and has been shown to correlate with high dysplasia grade in patients with premalignant disease . Combined expression of THBS2 and CA19‐9 demonstrated comparable diagnostic accuracy to distinguish patients with PDAC from HDs and patients with BD, in line with our results . These studies reported slightly different optimal cutoff values of THBS2 (42 and 28.9 ng/mL), almost comparable to the present study (40 ng/mL).…”

Liquid Biopsy Approach for Pancreatic Ductal Adenocarcinoma

“…In most of these studies, the candidate biomarker is compared with CA 19-9. Two studies investigated the diagnostic value of thrombospondin-2 (THBS2), which is a disulfide-linked homotrimetric glycoprotein that mediates cell-to-cell and cell-to-matrix interactions [128,129]. The levels of THBS2 were compared in patients with PDAC, as compared to patients with benign pancreatic diseases.…”

Coupled liquid biopsy and bioinformatics for pancreatic cancer early detection and precision prognostication

“…The expression levels of circulating tissue metalloproteinase inhibitor-1 (TIMP1) and Leucine-rich alpha-2-glycoprotein 1 (LRG1), thrombospondin-2 (THBS2) showed comparable diagnostic performance to CA19-9. While the diagnosis of early PDA could be significantly improved by combining the expression of these blood molecules with CA19-9 [ 13 , 14 ]. It is worth to mention here, similar to circulating proteins, blood metabolites demonstrated diagnostic potentials to detect PDA at early stage, either alone or in combination with CA19-9 or other proteins, as exemplified by recent studies which revealed that plasma metabolites, such as acetylspermidine, diacetylspermine, indole-derivatives, and lysophosphatidylcholines could distinguish PDA from healthy subjects and benign pancreatic disorders [ 15 , 16 ].…”