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Published on: November 5, 2020
Serum Metabolite Profiling for the Detection of Pancreatic Cancer: Results of a Large Independent Validation Study
Hirofumi Akita1, Shawn A Ritchie, Ichiro Takemasa
1From the *Department of Surgery, Osaka University Graduate School of Medicine, Suita City; †Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Osaka, Japan; and ‡Phenomenome Discoveries, Inc, Saskatoon, Saskatchewan, Canada.
Objectives:
To improve the detection of pancreatic cancer (PC), a robust diagnostic biomarker is essential. We have previously discovered 4 serum metabolites (PC-594, lysophosphatidylcholine, phosphatidylcholine, and sphingomyelin) in distinguishing patients with PC from healthy controls. Here, we report the results of our validation phase by using larger numbers of independent and blinded samples.
Methods:
We collected 3 mL of serum from 116 patients with PC and 138 healthy controls. Samples were blinded and expression of the 4 candidate metabolites in each sample was determined by triple quadrupole tandem mass spectrometry. We then used cutoffs established in the discovery phase to predict the disease state of each of the validation samples.
Results:
All 4 metabolites showed significantly lower expression in patients with PC compared with healthy controls. PC-594 showed 73.3% sensitivity and 92.0% specificity, whereas the other 3 metabolites showed 58.6% and 92.0%, 76.7% and 69.6%, and 58.6% and 81.9% sensitivity and specificity, respectively. Area under the receiver operating characteristic curve for PC-594 alone was 0.92, whereas a combination method using all 4 metabolites showed 86.2% sensitivity and 84.8% specificity.
Conclusions:
Our validation results confirmed that a reduction in PC-594, along with 3 other serum-based choline metabolites, is highly associated with PC.
