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Measurement of serum PODXL concentration for detection of pancreatic cancer.

ABSTRACT: Background:The aim of this study was to investigate the use of podocalyxin (PODXL) and secretoglobin family 1D, member 2 (SCGB1D2) expressions in whole blood as diagnostic biomarkers to distinguish between patients with pancreatic cancer and control participants, in comparison with serum cancer antigen 19-9 (CA19-9), which is the current clinical standard. Patients and methods:Flow cytometric analysis was performed to determine the expressions of PODXL and SCGB1D2 on the surface of cultured pancreatic cancer cells. Immunoblotting was performed to determine whether PODXL and SCGB1D2 were detectable in the media of cultured pancreatic cancer cells. A discovery-stage clinical study was performed in a cohort of 23 patients with pancreatic cancer and 51 control individuals without pancreatic disease who had been treated in the Department of Gastroenterology and Hepatology at Kochi Medical School Hospital from April 2014 to January 2016. Serum PODXL and SCGB1D2 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results:PODXL and SCGB1D2 accumulated in the protrusions of cultured pancreatic cancer cells, and they were detectable both on the cell surface and in the cultured media from these cells. The discovery-stage clinical study showed that the area under the receiver-operating characteristic curve (AUC) was 0.96 (95% confidence interval [CI] 0.91-1.000) for PODXL, 0.80 (95% CI 0.67-0.94) for SCGB1D2, and 0.78 (95% CI 0.66-0.90) for CA19-9. The AUC for PODXL was thus significantly higher than that for CA19-9 (P = 0.006). The combination of SCGB1D2 with CA19-9 did not significantly increase the AUC (0.83; 95% CI 0.70-0.96) compared with the AUC for either SCGB1D2 or CA19-9 alone (P = 0.563). Conclusion:PODXL may be a novel, non-invasive diagnostic biomarker for the detection of pancreatic cancer.

SUBMITTER: Taniuchi K

PROVIDER: S-EPMC5858829 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Measurement of serum PODXL concentration for detection of pancreatic cancer.

Taniuchi Keisuke K Tsuboi Makiko M Sakaguchi Masahiko M Saibara Toshiji T

OncoTargets and therapy 20180315

<h4>Background</h4>The aim of this study was to investigate the use of podocalyxin (PODXL) and secretoglobin family 1D, member 2 (SCGB1D2) expressions in whole blood as diagnostic biomarkers to distinguish between patients with pancreatic cancer and control participants, in comparison with serum cancer antigen 19-9 (CA19-9), which is the current clinical standard.<h4>Patients and methods</h4>Flow cytometric analysis was performed to determine the expressions of PODXL and SCGB1D2 on the surface o ...[more]

PMID: 29588598

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Project description:BackgroundThe prognosis of pancreatic cancer (PC) is one of the poorest among all cancers, due largely to the lack of methods for screening and early detection. New biomarkers for identifying high-risk or early-stage subjects could significantly impact PC mortality. The goal of this study was to find metabolic biomarkers associated with PC by using a comprehensive metabolomics technology to compare serum profiles of PC patients to healthy control subjects.MethodsA non-targeted metabolomics approach based on high-resolution, flow-injection Fourier transform ion cyclotron resonance mass spectrometry (FI-FTICR-MS) was used to generate comprehensive metabolomic profiles containing 2478 accurate mass measurements from the serum of Japanese PC patients (n=40) and disease-free subjects (n=50). Targeted flow-injection tandem mass spectrometry (FI-MS/MS) assays for specific metabolic systems were developed and used to validate the FI-FTICR-MS results. A FI-MS/MS assay for the most discriminating metabolite discovered by FI-FTICR-MS (PC-594) was further validated in two USA Caucasian populations; one comprised 14 PCs, six intraductal papillary mucinous neoplasms (IPMN) and 40 controls, and a second comprised 1000 reference subjects aged 30 to 80, which was used to create a distribution of PC-594 levels among the general population.ResultsFI-FTICR-MS metabolomic analysis showed significant reductions in the serum levels of metabolites belonging to five systems in PC patients compared to controls (all p<0.000025). The metabolic systems included 36-carbon ultra long-chain fatty acids, multiple choline-related systems including phosphatidylcholines, lysophosphatidylcholines and sphingomyelins, as well as vinyl ether-containing plasmalogen ethanolamines. ROC-AUCs based on FI-MS/MS of selected markers from each system ranged between 0.93 ±0.03 and 0.97 ±0.02. No significant correlations between any of the systems and disease-stage, gender, or treatment were observed. Biomarker PC-594 (an ultra long-chain fatty acid), was further validated using an independently-collected US Caucasian population (blinded analysis, n=60, p=9.9E-14, AUC=0.97 ±0.02). PC-594 levels across 1000 reference subjects showed an inverse correlation with age, resulting in a drop in the AUC from 0.99 ±0.01 to 0.90 ±0.02 for subjects aged 30 to 80, respectively. A PC-594 test positivity rate of 5.0% in low-risk reference subjects resulted in a PC sensitivity of 87% and a significant improvement in net clinical benefit based on decision curve analysis.ConclusionsThe serum metabolome of PC patients is significantly altered. The utility of serum metabolite biomarkers, particularly PC-594, for identifying subjects with elevated risk of PC should be further investigated.

Dataset Information

Measurement of serum PODXL concentration for detection of pancreatic cancer.

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Measurement of serum PODXL concentration for detection of pancreatic cancer.

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