Dataset Information

Clinical development of a blood biomarker using apolipoprotein-A2 isoforms for early detection of pancreatic cancer.

ABSTRACT:

Background

We have previously reported apolipoprotein A2-isoforms (apoA2-is) as candidate plasma biomarkers for early-stage pancreatic cancer. The aim of this study was the clinical development of apoA2-is.

Methods

We established a new enzyme-linked immunosorbent sandwich assay for apoA2-is under the Japanese medical device Quality Management System requirements and performed in vitro diagnostic tests with prespecified end points using 2732 plasma samples. The clinical equivalence and significance of apoA2-is were compared with CA19-9.

Results

The point estimate of the area under the curve to distinguish between pancreatic cancer (n = 106) and healthy controls (n = 106) was higher for apoA2-ATQ/AT [0.879, 95% confidence interval (CI): 0.832-0.925] than for CA19-9 (0.849, 95% CI 0.793-0.905) and achieved the primary end point. The cutoff apoA2-ATQ/AT of 59.5 μg/mL was defined based on a specificity of 95% in 2000 healthy samples, and the reliability of specificities was confirmed in two independent healthy cohorts as 95.3% (n = 106, 95% CI 89.4-98.0%) and 95.8% (n = 400, 95% CI 93.3-97.3%). The sensitivities of apoA2-ATQ/AT for detecting both stage I (47.4%) and I/II (50%) pancreatic cancers were higher than those of CA19-9 (36.8% and 46.7%, respectively). The combination of apoA2-ATQ/AT (cutoff, 59.5 μg/mL) and CA19-9 (37 U/mL) increased the sensitivity for pancreatic cancer to 87.7% compared with 69.8% for CA19-9 alone. The clinical performance of apoA2-is was blindly confirmed by the National Cancer Institute Early Detection Research Network.

Conclusions

The clinical performance of ApoA2-ATQ/AT as a blood biomarker is equivalent to or better than that of CA19-9.

SUBMITTER: Kashiro A

PROVIDER: S-EPMC10904523 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical development of a blood biomarker using apolipoprotein-A2 isoforms for early detection of pancreatic cancer.

Kashiro Ayumi A Kobayashi Michimoto M Oh Takanori T Miyamoto Mitsuko M Atsumi Jun J Nagashima Kengo K Takeuchi Keiko K Nara Satoshi S Hijioka Susumu S Morizane Chigusa C Kikuchi Shojiro S Kato Shingo S Kato Ken K Ochiai Hiroki H Obata Daisuke D Shizume Yuya Y Konishi Hiroshi H Nomura Yumiko Y Matsuyama Kotone K Xie Cassie C Wong Christin C Huang Ying Y Jung Giman G Srivastava Sudhir S Kutsumi Hiromu H Honda Kazufumi K

Journal of gastroenterology 20240123 3

<h4>Background</h4>We have previously reported apolipoprotein A2-isoforms (apoA2-is) as candidate plasma biomarkers for early-stage pancreatic cancer. The aim of this study was the clinical development of apoA2-is.<h4>Methods</h4>We established a new enzyme-linked immunosorbent sandwich assay for apoA2-is under the Japanese medical device Quality Management System requirements and performed in vitro diagnostic tests with prespecified end points using 2732 plasma samples. The clinical equivalence ...[more]

PMID: 38261000

Similar Datasets

Project description:CA19-9, which is currently in clinical use as a pancreatic ductal adenocarcinoma (PDAC) biomarker, has limited performance in detecting early-stage disease. We and others have identified protein biomarker candidates that have the potential to complement CA19-9. We have carried out sequential validations starting with 17 protein biomarker candidates to determine which markers and marker combination would improve detection of early-stage disease compared with CA19-9 alone. Candidate biomarkers were subjected to enzyme-linked immunosorbent assay based sequential validation using independent multiple sample cohorts consisting of PDAC cases (n = 187), benign pancreatic disease (n = 93), and healthy controls (n = 169). A biomarker panel for early-stage PDAC was developed based on a logistic regression model. All statistical tests for the results presented below were one-sided. Six out of the 17 biomarker candidates and CA19-9 were validated in a sample set consisting of 75 PDAC patients, 27 healthy subjects, and 19 chronic pancreatitis patients. A second independent set of 73 early-stage PDAC patients, 60 healthy subjects, and 74 benign pancreatic disease patients (combined validation set) yielded a model that consisted of TIMP1, LRG1, and CA19-9. Additional blinded testing of the model was done using an independent set of plasma samples from 39 resectable PDAC patients and 82 matched healthy subjects (test set). The model yielded areas under the curve (AUCs) of 0.949 (95% confidence interval [CI] = 0.917 to 0.981) and 0.887 (95% CI = 0.817 to 0.957) with sensitivities of 0.849 and 0.667 at 95% specificity in discriminating early-stage PDAC vs healthy subjects in the combined validation and test sets, respectively. The performance of the biomarker panel was statistically significantly improved compared with CA19-9 alone (P < .001, combined validation set; P = .008, test set). The addition of TIMP1 and LRG1 immunoassays to CA19-9 statistically significantly improves the detection of early-stage PDAC.

Dataset Information

Clinical development of a blood biomarker using apolipoprotein-A2 isoforms for early detection of pancreatic cancer.

Background

Methods

Results

Conclusions

Publications

Clinical development of a blood biomarker using apolipoprotein-A2 isoforms for early detection of pancreatic cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets