Dataset Information

Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms.

ABSTRACT: We recently reported that circulating apolipoprotein AII (apoAII) isoforms apoAII-ATQ/AT (C-terminal truncations of the apoAII homo-dimer) decline significantly in pancreatic cancer and thus might serve as plasma biomarkers for the early detection of this disease. We report here the development of novel enzyme-linked immunosorbent assays (ELISAs) for measurement of apoAII-ATQ/AT and their clinical applicability for early detection of pancreatic cancer. Plasma and serum concentrations of apoAII-ATQ/AT were measured in three independent cohorts, which comprised healthy control subjects and patients with pancreatic cancer and gastroenterologic diseases (n?=?1156). These cohorts included 151 cases of stage I/II pancreatic cancer. ApoAII-ATQ/AT not only distinguished the early stages of pancreatic cancer from healthy controls but also identified patients at high risk for pancreatic malignancy. AUC values of apoAII-ATQ/AT to detect early stage pancreatic cancer were higher than those of CA19-9 in all independent cohorts. ApoAII-ATQ/AT is a potential biomarker for screening patients for the early stage of pancreatic cancer and identifying patients at risk for pancreatic malignancy (161 words).

SUBMITTER: Honda K

PROVIDER: S-EPMC4637825 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms.

Honda Kazufumi K Kobayashi Michimoto M Okusaka Takuji T Rinaudo Jo Ann JA Huang Ying Y Marsh Tracey T Sanada Mitsuaki M Sasajima Yoshiyuki Y Nakamori Shoji S Shimahara Masashi M Ueno Takaaki T Tsuchida Akihiko A Sata Naohiro N Ioka Tatsuya T Yasunami Yohichi Y Kosuge Tomoo T Miura Nami N Kamita Masahiro M Sakamoto Takako T Shoji Hirokazu H Jung Giman G Srivastava Sudhir S Yamada Tesshi T

Scientific reports 20151109

We recently reported that circulating apolipoprotein AII (apoAII) isoforms apoAII-ATQ/AT (C-terminal truncations of the apoAII homo-dimer) decline significantly in pancreatic cancer and thus might serve as plasma biomarkers for the early detection of this disease. We report here the development of novel enzyme-linked immunosorbent assays (ELISAs) for measurement of apoAII-ATQ/AT and their clinical applicability for early detection of pancreatic cancer. Plasma and serum concentrations of apoAII-A ...[more]

PMID: 26549697

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Project description:BackgroundBlood-based biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) are urgently needed. Current biomarkers lack high sensitivity and specificity for population screening. The gold-standard biomarker, CA 19-9, also fails to demonstrate the predictive value necessary for early detection.MethodsTo validate a functional genomics-based plasma migration signature biomarker panel, plasma tissue factor pathway inhibitor (TFPI), tenascin C (TNC-FN III-C), and CA 19-9 levels were measured by enzyme-linked immunosorbent assays in three early-stage PDAC plasma cohorts, including two independent blinded validation cohorts containing a total of 43 stage I, 163 stage II, 86 chronic pancreatitis, 31 acute biliary obstruction, and 108 controls. Logistic regression models developed classification rules combining TFPI and/or TNC-FN III-C with CA 19-9 for patient cases and control subjects, with or without adjustment for age and diabetes status. Model classification performance was evaluated and analyses repeated among subpopulations without diabetes and pancreatitis history. Two-sided P values were calculated using bootstrap method.ResultsThe TFPI/TNC-FN III-C/CA 19-9 panel improved CA 19-9 performance in all early-stage cohorts, including discriminating stage IA/IB/IIA, stage IIB, and all early-stage cancer from healthy controls. Statistical significance was reached for a number of subcohorts, including for all early-stage cancer vs healthy controls (cohort 1 AUC = 0.92, 95% CI = 0.86 to 0.96, P = .04; cohort 3 AUC = 0.83, 95% CI = 0.76 to 0.89, P = .045). Among subcohorts without diabetes and pancreatitis history, the panel approaches potential clinical utility for early detection to discriminate early-stage PDAC from healthy controls including an area under the curve (AUC) of 0.87 (95% CI = 0.77 to 0.95) for stage I/IIA, an AUC of 0.93 (95% CI = 0.87 to 0.98) for stage IIB, and a statistically significant AUC of 0.89 (95% CI = 0.82 to 0.95) for all early-stage cancer ( P = .03).ConclusionsTFPI/TNC-FN III-C migration signature adds statistically significantly to CA 19-9's predictive power to detect early-stage PDAC and may have clinical utility for early detection of surgically resectable PDAC, as well as for enhanced survival from this routinely lethal cancer.

Dataset Information

Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms.

Publications

Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms.

Similar Datasets

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