CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation.

Published on Apr 15, 2019in International Journal of Cancer5.145
· DOI :10.1002/IJC.31900
Kazufumi Honda40
Estimated H-index: 40
(Japan Agency for Medical Research and Development),
Verena Katzke35
Estimated H-index: 35
(DKFZ: German Cancer Research Center)
+ 39 AuthorsRudolf Kaaks151
Estimated H-index: 151
(DKFZ: German Cancer Research Center)
Sources
Abstract
Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform (“ApoA2-ATQ/AT”), alone and in combination with carbohydrate antigen 19–9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6–18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6–18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6–18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging. (Less)
📖 Papers frequently viewed together
49 Citations
14 Citations
108 Citations
References28
Newest
#1Francesca Lupo (University of Verona)H-Index: 5
#2Geny PiroH-Index: 17
Last. Carmine CarboneH-Index: 20
view all 18 authors...
: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality among adults in developed countries. The discovery of the most common genetic alterations as well as the development of organoid models of pancreatic cancer have provided insight into the fundamental pathways driving tumor progression from a normal cell to non-invasive precursor lesion and finally to widely metastatic disease, offering new opportunities for identifying the key driver of cancer evolut...
4 CitationsSource
#1Masayuki Akita (Kobe University)H-Index: 10
#2Tetsuo Ajiki (Kobe University)H-Index: 26
Last. Takumi Fukumoto (Kobe University)H-Index: 25
view all 9 authors...
Purposes Resected bile duct cancers often relapse during postoperative follow-up. The aim of this study was to detect predictors of early recurrence in patients with extrahepatic bile duct cancer.
3 CitationsSource
#1Zhen Huo (SJTU: Shanghai Jiao Tong University)H-Index: 8
#2Zhihao Shi (SJTU: Shanghai Jiao Tong University)H-Index: 1
Last. Baiyong Shen (SJTU: Shanghai Jiao Tong University)H-Index: 27
view all 12 authors...
: BACKGROUND Robotic pancreaticoduodenectomy (RPD) is a novel type of minimally invasive surgery to treat tumors located at the head of the pancreas. This study aimed to construct a novel prediction model for predicting selection preference for RPD in a Chinese single medical center population. MATERIAL AND METHODS The clinical data from 451 pancreatic ductal adenocarcinoma patients were collected and analyzed from January 2013 to December 2016. Twenty-three items affecting clinical strategies w...
Source
#1Deirdre Kruger (University of the Witwatersrand)H-Index: 8
#2Yandiswa Y Yako (University of the Witwatersrand)H-Index: 12
Last. Martin Smith (University of the Witwatersrand)H-Index: 12
view all 5 authors...
Background Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenged by the absence of accurate early diagnostic and prognostic biomarkers. CA19-9 is the established, diagnostic tumour marker in PDAC, despite its limitations. Effective primary screening using circulating biomarker panels have only been considered in a handful of studies and we investigated whether combinations of inflammatory cytokines and angiogenic factors in multivariate logistic models could facilitate earlier...
5 CitationsSource
#1Zhuo-Xian Rong (CSU: Central South University)H-Index: 3
#2Zhi Li (CSU: Central South University)H-Index: 14
Last. Lun-Quan Sun (CSU: Central South University)H-Index: 32
view all 14 authors...
Intrahepatic cholangiocarcinoma (ICC) ranks as the second most malignant type of primary liver cancer with a high degree of incidence and a very poor prognosis. Fat mass and obesity-associated protein (FTO) functions as an eraser of the RNA m6A modification, but its roles in ICC tumorigenesis and development remain unknown. We showed here that the protein level of FTO was downregulated in clinical ICC samples and cell lines and that FTO expression was inversely correlated with the expression of ...
38 CitationsSource
#1Seetharaman Balasenthil (University of Texas MD Anderson Cancer Center)H-Index: 25
#2Ying Huang (Fred Hutchinson Cancer Research Center)H-Index: 31
Last. Ann M. Killary (University of Texas MD Anderson Cancer Center)H-Index: 13
view all 14 authors...
Abstract Blood-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. To 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 mea...
40 CitationsSource
#1Michela Capello (University of Texas MD Anderson Cancer Center)H-Index: 19
#2Leonidas E. Bantis (University of Texas MD Anderson Cancer Center)H-Index: 11
Last. Samir M. HanashH-Index: 101
view all 20 authors...
Abstract 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 bioma...
77 CitationsSource
Given the low incidence of pancreatic cancer in the general population, screening of pancreatic cancer in the general population using invasive modalities is not feasible. Combination of invasive screening with noninvasive biomarkers for pancreatic cancer and its precancerous lesions has the potential to reduce mortality due to pancreatic cancer. In this review, we focus on biomarkers found in the blood that can indicate early-stage pancreatic cancer, and we discuss current strategies for screen...
14 CitationsSource
#1Barbara J. KennerH-Index: 5
#2Suresh T. Chari (Mayo Clinic)H-Index: 103
Last. Ann E. GoldbergH-Index: 2
view all 8 authors...
The implementation of effective early detection programs has significantly improved treatment, prognosis, and life expectancy in breast, prostate, and colorectal cancers. Early-detection methods need to be developed for pancreatic ductal adenocarcinoma (PDAC), where progress during the past decades has remained slow. Addressing this need, the forum “Early Detection: Lessons Learned from Other Cancers” was held in November 2015 and presented by the Kenner Family Research Fund in partnership with ...
24 CitationsSource
#1Margaret S. PepeH-Index: 87
#2Holly JanesH-Index: 15
Last. Jørgen Hilden (UCPH: University of Copenhagen)H-Index: 39
view all 6 authors...
BACKGROUND: Many cancer biomarker research studies seek to develop markers that can accurately detect or predict future onset of disease. To design and evaluate these studies, one must specify the levels of accuracy sought. However, justified target levels are rarely available. METHODS: We describe a way to calculate target levels of sensitivity and specificity for a biomarker intended to be applied in a defined clinical context. The calculation requires knowledge of the prevalence or incidence ...
40 CitationsSource
Cited By19
Newest
#1John T. Wilkins (NU: Northwestern University)H-Index: 27
#2Henrique S. Seckler (NU: Northwestern University)H-Index: 7
Last. Allan D. Sniderman (MUHC: McGill University Health Centre)
view all 12 authors...
Background ApoAI (apolipoproteins AI) and apoAII (apolipoprotein AII) are structural and functional proteins of high‐density lipoproteins (HDL) which undergo post‐translational modifications at spe...
Source
Source
#1Xuping Wu (Nanjing University of Chinese Medicine)
Last. Yongxiang Yi (Nanjing University of Chinese Medicine)
view all 6 authors...
Hepatic cancer is often amenable to surgery, including percutaneous ablation, trans-arterial chemoembolization. However, in metastatic cases, surgery is often not an effective option. Chemotherapy as a conventional clinical method for treatment of malignant diseases may be useful in such cases, but it is likewise not always able to slow or halt progression, therefore novel approaches for treatment of hepatic cancer are needed. Current research suggests that molecular tumor markers (TM) can play ...
Source
Background & Aims There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established. Methods CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched c...
7 CitationsSource
#1Laura Kane (Trinity College, Dublin)
Last. Stephen G. Maher (Trinity College, Dublin)H-Index: 17
view all 5 authors...
Pancreatic cancer (PC) is among the most aggressive types of cancer, having caused over 495,000 deaths worldwide in 2020, with increasing annual incidence. Pancreatic cystic lesions (PCLs) are protrusions found within or on the surface of the pancreas, and in many cases have the potential to become malignant. Current methods of characterising PCLs are imperfect and there is a profound need for improved diagnostic algorithms. This review highlights the importance of biological markers in the cont...
Source
#1Natalia Monteiro Calanzani (University of Cambridge)H-Index: 16
#2Paige Druce (University of Melbourne)H-Index: 1
Last. Fiona M Walter (University of Cambridge)H-Index: 50
view all 13 authors...
Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, and most patients presenting with these symptoms will not have cancer. Substantial investment has been made to develop biomarkers for cancer detection, but few have reached routine clinical practice. We aimed to identify novel biomarkers for upper GI cancers which have been sufficiently validated to be ready for evaluation in low-prevalence populations. We systematical...
4 CitationsSource
#1Shrey Modi (UM: University of Miami)H-Index: 12
#2Devika Kir (UM: University of Miami)H-Index: 6
Last. Ashok K. Saluja (UM: University of Miami)H-Index: 71
view all 3 authors...
Source
#1Silvana Debernardi (QMUL: Queen Mary University of London)H-Index: 17
#2Harrison O’Brien (QMUL: Queen Mary University of London)H-Index: 1
Last. Tatjana Crnogorac-Jurcevic (QMUL: Queen Mary University of London)H-Index: 34
view all 16 authors...
Publisher Copyright: © 2020 Debernardi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
4 CitationsSource
#1Yu Sato (Kobe University)H-Index: 3
#2Takashi Kobayashi (Kobe University)H-Index: 14
Last. Kengo NagashimaH-Index: 21
view all 18 authors...
Apolipoprotein A2-ATQ/AT (apoA2-ATQ/AT) has been identified as a minimally invasive biomarker for detecting pancreatic cancer (PC) and high-risk (HR) individuals for PC. To establish an efficient enrichment strategy for HR, we carried out a plasma apoA2-ATQ/AT level-based prospective screening study among the general population. The subjects for the screening study were recruited at six medical check-up facilities in Japan between October 2015 and January 2017. We evaluated the positive predicti...
2 CitationsSource
#1Tomomi Kihara (Osaka University)H-Index: 1
#2Kazumasa Yamagishi (University of Tsukuba)H-Index: 58
Last. Shoichiro TsuganeH-Index: 106
view all 13 authors...
Aim The fact that low concentrations of high-density lipoprotein cholesterol are associated with the risk of cardiovascular disease is well known, but high-density lipoprotein metabolism has not been fully understood. Apolipoprotein A2 (ApoA2) is the second-most dominant apolipoprotein of high-density lipoprotein. We tested the hypothesis that ApoA2 isoforms are inversely associated with myocardial infarction. Methods We measured the plasma levels of three ApoA2 isoforms (ApoA2-ATQ/ATQ, ApoA2-AT...
Source