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Plasma biomarker for detecting early stage and risk disease of pancreatic cancer by Apolipoprotein-A2 isoforms
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Abstracts / Pancreatology 16 (2016) S1eS192
group, only 7.5% of the patients who received TP with IAT had persistent pain (Chinnakotla S, et al. Ann Surg 2015). We Japanese pancreatologists strongly recognize that TP with IAT is an excessive surgery for CP, but it is a fact that there are very few CP patients who need TP with IAT, like a patient who underwent this treatment in Osaka University in 2013. Should JPS discuss how to deal with TP with IAT as one of the treatments for CP?
F-024. Plasma biomarker for detecting early stage and risk disease of pancreatic cancer by Apolipoprotein-A2 isoforms Kazufumi Honda 1, 2, 3, Michimoto Kobayashi 4, Takuji Okusaka 5, Chigusa Morizane 5, Jo Ann Rinaudo 6, Ying Huang 7, Tracey Marsh 7, Shoji Nakamori 8, Masashi Shimahara 9, Takaaki Ueno 9, Akihiko Tsuchida 10, Naohiro Sata 11, Tatsuya Ioka 12, Tomoo Kosuge 13, Yohichi Yasunami 14, Masaru Yoshida 2, 3, Takeshi Azuma 3, Sudhir Srivastava 6, Tesshi Yamada 1 1 Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Japan 2 Department of Gastroenterology, Graduate School of Medicine Kobe University, Japan 3 Japan Agency for Medical Research and Development (AMED), CRESTAMED, Japan 4 New Frontiers Research Laboratories, Toray Industries, Inc., Japan 5 Divsion of Pancreatic Oncology, National Cancer Center Hospital, Japan 6 Division of Cancer Prevention, National Cancer Institute, United States 7 Public Health Science Division, Fred Hutchinson Cancer Center, United States 8 Department of Surgery, Osaka National Hospital, Japan 9 Department of Oral and Maxillofacial Surgery, Osaka Medical University, Japan 10 Department of Gastroenterological and Pediatric Surgery, Tokyo Medical University, Japan 11 Department of Surgery, Jichi Medical University, Japan 12 Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan 13 Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Japan 14 Department of Regenerative Medicine and Transplantation, Fukuoka University Faculty of Medicine, Japan
We have previously reported that levels of circulating apolipoprotein (apo) A2 isoforms apoA2-ATQ/AT (C-terminal truncations of the apoA2 homo-dimer) decline significantly in pancreatic cancer and thus might serve as plasma biomarkers for early detection of this pathology. We report here the development of novel enzyme-linked immunosorbent assays (ELISAs) for measuring apoA2-ATQ/AT levels and clinical applicability for early detection of pancreatic cancer. Plasma and serum concentrations of apoA2-ATQ/AT were measured in three independent cohorts, which comprised healthy control subjects and patients with pancreatic cancer or gastroenterologic disease (n¼1156; two Japanese cohorts and one American cohort). These cohorts included 151 cases of stage I/II pancreatic cancer. Significant reductions in apoA2-ATQ/AT levels were recognized in patients with pancreatic cancer in comparison with healthy controls in both independent Japanese cohorts (p¼1.34*1018 and 5.09*1039). Areas under the receiver operating characteristic curve (AUC) were >0.92 for distinguishing patients with stage I/II pancreatic cancer from healthy controls in the Japanese cohorts. The AUCs of apoA2-ATQ/AT to distinguish patients with pancreatic cancer from healthy controls were higher than those of carbohydrate antigen (CA) 19-9 in both Japanese cohorts. Better discrimination of pancreatic cancer was also observed with apoA2-ATQ/AT than with CA19-9 in the blind test using the pancreatic cancer reference set of the US National Cancer Institute's Early Detection Research Network; combining apoA2-ATQ/AT with CA19-9 led to significantly improved AUC compared to CA19-9 alone. ApoA2-ATQ/AT is a potential biomarker for screening patients for early stages of pancreatic cancer and identifying patients at risk for pancreatic malignancy.
F-025. Functional polymorphisms in the CDKN2A generegion affect pancreatic cancer risk Federico Canzian 1, Manuela Pastore 1, 2, Manuel Gentiluomo 1, 2, Raffaele Pezzilli 3, Ugo Boggi 4, Gianfranco Delle Fave 5, Renata TalarWojnarowska 6, Juozas Kupcinskas 7, Oliver Strobel 8, Pavel Vodicka 9, Hermann Brenner 10, Kay-Tee Khaw 11, Tim Key 12, Stefano Landi 2, Francesca Tavano 13, John Neoptolemos 14, Andrea Mambrini 15, Aldo Scarpa 16, Pavel Soucek 17, Maria Gazouli 18, Anna Caterina Milanetto 19, Cosmeri Rizzato 1, 20, Yogesh K. Vashist 21, Frederike Dijk 22, Daniele Campa 1, 2 1 Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Germany 2 Department of Biology, University of Pisa, Italy 3 Pancreas Unit, Department of Digestive Diseases, Sant'OrsolaMalpighi Hospital, Italy 4 Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Italy 5 Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University of Rome, Italy 6 Department of Digestive Tract, Diseases, Medical University of Lodz, Poland 7 Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Lithuania 8 Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Germany 9 Department Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences, Czech Republic 10 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Germany 11 University of Cambridge School of Clinical Medicine, United Kingdom 12 Cancer Epidemiology Unit, University of Oxford, United Kingdom 13 Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, Italy 14 National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, United Kingdom 15 Oncology Department, ASL1 Massa Carrara, Italy 16 ARC-Net Applied Research on Cancer Center, University and Hospital Trust of Verona, Italy 17 Toxicogenomics Unit, Center for Toxicology and Health Safety, National Institute of Public Health, Czech Republic 18 Department of Basic Medical Science, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Greece 19 Pancreatic and Digestive Endocrine Surgery Group, University of Padua, Italy 20 Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy 21 Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Germany 22 Department of Pathology, Academic Medical Center, University of Amsterdam, Netherlands
There are compelling epidemiologic and molecular evidences pointing to a key role for the CDKN2A gene in pancreatic cancer etiology. In particular, CDKN2A is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familial pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated single nucleotide polymorphisms (SNPs) in the 9p21.3 region, that includes the CDNK2A gene, are associated with the risk of cancer in various organs. This region includes also SNPs associated with the risk of type 2 diabetes mellitus, which has been proposed as a risk factor for pancreatic cancer, suggesting a possible role of the 9p21.3 region as a genetic link between the two diseases. However, association between the common genetic variability in this region and pancreatic cancer risk has never been studied in detail. We sought to fill this gap in a case-control study genotyping 13 SNPs in 2,857 pancreatic ductal
Abstracts / Pancreatology 16 (2016) S1eS192
group, only 7.5% of the patients who received TP with IAT had persistent pain (Chinnakotla S, et al. Ann Surg 2015). We Japanese pancreatologists strongly recognize that TP with IAT is an excessive surgery for CP, but it is a fact that there are very few CP patients who need TP with IAT, like a patient who underwent this treatment in Osaka University in 2013. Should JPS discuss how to deal with TP with IAT as one of the treatments for CP?
F-024. Plasma biomarker for detecting early stage and risk disease of pancreatic cancer by Apolipoprotein-A2 isoforms Kazufumi Honda 1, 2, 3, Michimoto Kobayashi 4, Takuji Okusaka 5, Chigusa Morizane 5, Jo Ann Rinaudo 6, Ying Huang 7, Tracey Marsh 7, Shoji Nakamori 8, Masashi Shimahara 9, Takaaki Ueno 9, Akihiko Tsuchida 10, Naohiro Sata 11, Tatsuya Ioka 12, Tomoo Kosuge 13, Yohichi Yasunami 14, Masaru Yoshida 2, 3, Takeshi Azuma 3, Sudhir Srivastava 6, Tesshi Yamada 1 1 Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Japan 2 Department of Gastroenterology, Graduate School of Medicine Kobe University, Japan 3 Japan Agency for Medical Research and Development (AMED), CRESTAMED, Japan 4 New Frontiers Research Laboratories, Toray Industries, Inc., Japan 5 Divsion of Pancreatic Oncology, National Cancer Center Hospital, Japan 6 Division of Cancer Prevention, National Cancer Institute, United States 7 Public Health Science Division, Fred Hutchinson Cancer Center, United States 8 Department of Surgery, Osaka National Hospital, Japan 9 Department of Oral and Maxillofacial Surgery, Osaka Medical University, Japan 10 Department of Gastroenterological and Pediatric Surgery, Tokyo Medical University, Japan 11 Department of Surgery, Jichi Medical University, Japan 12 Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan 13 Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Japan 14 Department of Regenerative Medicine and Transplantation, Fukuoka University Faculty of Medicine, Japan
We have previously reported that levels of circulating apolipoprotein (apo) A2 isoforms apoA2-ATQ/AT (C-terminal truncations of the apoA2 homo-dimer) decline significantly in pancreatic cancer and thus might serve as plasma biomarkers for early detection of this pathology. We report here the development of novel enzyme-linked immunosorbent assays (ELISAs) for measuring apoA2-ATQ/AT levels and clinical applicability for early detection of pancreatic cancer. Plasma and serum concentrations of apoA2-ATQ/AT were measured in three independent cohorts, which comprised healthy control subjects and patients with pancreatic cancer or gastroenterologic disease (n¼1156; two Japanese cohorts and one American cohort). These cohorts included 151 cases of stage I/II pancreatic cancer. Significant reductions in apoA2-ATQ/AT levels were recognized in patients with pancreatic cancer in comparison with healthy controls in both independent Japanese cohorts (p¼1.34*1018 and 5.09*1039). Areas under the receiver operating characteristic curve (AUC) were >0.92 for distinguishing patients with stage I/II pancreatic cancer from healthy controls in the Japanese cohorts. The AUCs of apoA2-ATQ/AT to distinguish patients with pancreatic cancer from healthy controls were higher than those of carbohydrate antigen (CA) 19-9 in both Japanese cohorts. Better discrimination of pancreatic cancer was also observed with apoA2-ATQ/AT than with CA19-9 in the blind test using the pancreatic cancer reference set of the US National Cancer Institute's Early Detection Research Network; combining apoA2-ATQ/AT with CA19-9 led to significantly improved AUC compared to CA19-9 alone. ApoA2-ATQ/AT is a potential biomarker for screening patients for early stages of pancreatic cancer and identifying patients at risk for pancreatic malignancy.
F-025. Functional polymorphisms in the CDKN2A generegion affect pancreatic cancer risk Federico Canzian 1, Manuela Pastore 1, 2, Manuel Gentiluomo 1, 2, Raffaele Pezzilli 3, Ugo Boggi 4, Gianfranco Delle Fave 5, Renata TalarWojnarowska 6, Juozas Kupcinskas 7, Oliver Strobel 8, Pavel Vodicka 9, Hermann Brenner 10, Kay-Tee Khaw 11, Tim Key 12, Stefano Landi 2, Francesca Tavano 13, John Neoptolemos 14, Andrea Mambrini 15, Aldo Scarpa 16, Pavel Soucek 17, Maria Gazouli 18, Anna Caterina Milanetto 19, Cosmeri Rizzato 1, 20, Yogesh K. Vashist 21, Frederike Dijk 22, Daniele Campa 1, 2 1 Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Germany 2 Department of Biology, University of Pisa, Italy 3 Pancreas Unit, Department of Digestive Diseases, Sant'OrsolaMalpighi Hospital, Italy 4 Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Italy 5 Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University of Rome, Italy 6 Department of Digestive Tract, Diseases, Medical University of Lodz, Poland 7 Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Lithuania 8 Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Germany 9 Department Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences, Czech Republic 10 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Germany 11 University of Cambridge School of Clinical Medicine, United Kingdom 12 Cancer Epidemiology Unit, University of Oxford, United Kingdom 13 Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, Italy 14 National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, United Kingdom 15 Oncology Department, ASL1 Massa Carrara, Italy 16 ARC-Net Applied Research on Cancer Center, University and Hospital Trust of Verona, Italy 17 Toxicogenomics Unit, Center for Toxicology and Health Safety, National Institute of Public Health, Czech Republic 18 Department of Basic Medical Science, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Greece 19 Pancreatic and Digestive Endocrine Surgery Group, University of Padua, Italy 20 Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy 21 Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Germany 22 Department of Pathology, Academic Medical Center, University of Amsterdam, Netherlands
There are compelling epidemiologic and molecular evidences pointing to a key role for the CDKN2A gene in pancreatic cancer etiology. In particular, CDKN2A is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familial pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated single nucleotide polymorphisms (SNPs) in the 9p21.3 region, that includes the CDNK2A gene, are associated with the risk of cancer in various organs. This region includes also SNPs associated with the risk of type 2 diabetes mellitus, which has been proposed as a risk factor for pancreatic cancer, suggesting a possible role of the 9p21.3 region as a genetic link between the two diseases. However, association between the common genetic variability in this region and pancreatic cancer risk has never been studied in detail. We sought to fill this gap in a case-control study genotyping 13 SNPs in 2,857 pancreatic ductal