Biomarkers for early diagnosis of pancreatic

Pancreatic ductal adenocarcinoma is an aggressive malignancy with a 5-year survival rate of approximately 5%. The lack of established strategies for early detection contributes to this poor prognosis. Although several novel candidate biomarkers have been proposed for earlier diagnosis, none have been adopted into routine clinical use. In this review, the authors examine the challenges associated with finding new pancreatic cancer diagnostic biomarkers and explore why translation of biomarker research for patient benefit has thus far failed. The authors also review recent progress and highlight advances in the understanding of the biology of pancreatic cancer that may lead to improvements in biomarker detection and

[1]  W. Greenhalf,et al.  Incidence of Post-ERCP Pancreatitis From Direct Pancreatic Juice Collection in Hereditary Pancreatitis and Familial Pancreatic Cancer Before and After the Introduction of Prophylactic Pancreatic Stents and Rectal Diclofenac , 2015, Pancreas.

[2]  Benjamin D. Smith,et al.  Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. , 2014, Cancer research.

[3]  W. Greenhalf,et al.  Serum cytokine biomarker panels for discriminating pancreatic cancer from benign pancreatic disease , 2014, Molecular Cancer.

[4]  Zhe Huang,et al.  Diagnostic value of serum carbohydrate antigen 19-9 in pancreatic cancer: a meta-analysis , 2014, Tumor Biology.

[5]  T. Wilt,et al.  Pancreatic adenocarcinoma: treating a systemic disease with systemic therapy. , 2014, Journal of the National Cancer Institute.

[6]  Mack T. Ruffin,et al.  Glycoprotein Biomarker Panel for Pancreatic Cancer Discovered by Quantitative Proteomics Analysis , 2014, Journal of proteome research.

[7]  Thomas J George,et al.  Capture, release and culture of circulating tumor cells from pancreatic cancer patients using an enhanced mixing chip. , 2014, Lab on a chip.

[8]  Lotty Hooft,et al.  Reporting quality of diagnostic accuracy studies: a systematic review and meta-analysis of investigations on adherence to STARD , 2013, Evidence-Based Medicine.

[9]  Ash A. Alizadeh,et al.  An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage , 2013, Nature Medicine.

[10]  D. Goldenberg,et al.  Mapping PAM4 (clivatuzumab), a monoclonal antibody in clinical trials for early detection and therapy of pancreatic ductal adenocarcinoma, to MUC5AC mucin , 2013, Molecular Cancer.

[11]  C. Borrebaeck,et al.  Modelling the benefits of early diagnosis of pancreatic cancer using a biomarker signature , 2013, International journal of cancer.

[12]  Edward J Park,et al.  Detection and isolation of circulating tumor cells: principles and methods. , 2013, Biotechnology advances.

[13]  P. Vineis,et al.  Autoantibodies to Ezrin are an early sign of pancreatic cancer in humans and in genetically engineered mouse models , 2013, Journal of Hematology & Oncology.

[14]  E. Diamandis,et al.  Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9 , 2013, BMC Cancer.

[15]  U. Ballehaninna,et al.  Biomarkers for pancreatic cancer: promising new markers and options beyond CA 19-9 , 2013, Tumor Biology.

[16]  D. Chia,et al.  Role of Pancreatic Cancer-derived Exosomes in Salivary Biomarker Development* , 2013, The Journal of Biological Chemistry.

[17]  C. Langmead,et al.  The Marker State Space (MSS) Method for Classifying Clinical Samples , 2013, PloS one.

[18]  M. Kanda,et al.  Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. , 2013, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[19]  Jiong Chen,et al.  Expression and clinical significance of complement C3, complement C4b1 and apolipoprotein E in pancreatic cancer , 2013, Oncology letters.

[20]  H. Friess,et al.  iTRAQ reveals candidate pancreatic cancer serum biomarkers: influence of obstructive jaundice on their performance , 2013, British Journal of Cancer.

[21]  R. Hruban,et al.  PAM4 enzyme immunoassay alone and in combination with CA 19‐9 for the detection of pancreatic adenocarcinoma , 2013, Cancer.

[22]  J. Berlin,et al.  Changing the Way We Do Business: Recommendations to Accelerate Biomarker Development in Pancreatic Cancer , 2013, Clinical Cancer Research.

[23]  C. Andersen,et al.  Circulating U2 small nuclear RNA fragments as a novel diagnostic biomarker for pancreatic and colorectal adenocarcinoma , 2013, International journal of cancer.

[24]  Zhiwei Wang,et al.  Identifying Biomarkers and Drug Targets Using Systems Biology Approaches for Pancreatic Cancer. , 2012, Pancreatic disorders & therapy.

[25]  S. Choi,et al.  Serum CA19–9, cathepsin D, and matrix metalloproteinase‐7 as a diagnostic panel for pancreatic ductal adenocarcinoma , 2012, Proteomics.

[26]  P. Bracci,et al.  Serum autoantibodies to pancreatic cancer antigens as biomarkers of pancreatic cancer in a San Francisco Bay Area case–control study , 2012, Cancer.

[27]  S. Batra,et al.  Early diagnosis of pancreatic cancer: challenges and new developments. , 2012, Biomarkers in medicine.

[28]  M. Kanda,et al.  Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts , 2012, Gut.

[29]  W. Greenhalf,et al.  New biomarkers and targets in pancreatic cancer and their application to treatment , 2012, Nature Reviews Gastroenterology &Hepatology.

[30]  A. Adai,et al.  Global microRNA expression profiling of microdissected tissues identifies miR‐135b as a novel biomarker for pancreatic ductal adenocarcinoma , 2012, International journal of cancer.

[31]  A. Adai,et al.  miRNA Biomarkers in Cyst Fluid Augment the Diagnosis and Management of Pancreatic Cysts , 2012, Clinical Cancer Research.

[32]  D. Tuveson,et al.  Claudin-4-targeted optical imaging detects pancreatic cancer and its precursor lesions , 2012, Gut.

[33]  David R Goodlett,et al.  Multiplex targeted proteomic assay for biomarker detection in plasma: a pancreatic cancer biomarker case study. , 2012, Journal of proteome research.

[34]  Joshua M. Kunken,et al.  Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers , 2012, Physical biology.

[35]  D. Tuveson,et al.  Understanding Metastasis in Pancreatic Cancer: A Call for New Clinical Approaches , 2012, Cell.

[36]  Sepp Kaul,et al.  Multimarker Gene Analysis of Circulating Tumor Cells in Pancreatic Cancer Patients: A Feasibility Study , 2012, Oncology.

[37]  Maximilian Reichert,et al.  EMT and Dissemination Precede Pancreatic Tumor Formation , 2012, Cell.

[38]  L Khoja,et al.  A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker , 2011, British Journal of Cancer.

[39]  M. Bouvet,et al.  Marker expression in circulating cancer cells of pancreatic cancer patients. , 2011, The Journal of surgical research.

[40]  R. Andersson,et al.  Proteome-based biomarkers in pancreatic cancer. , 2011, World journal of gastroenterology.

[41]  Michael Goggins,et al.  MicroRNA Alterations of Pancreatic Intraepithelial Neoplasias , 2011, Clinical Cancer Research.

[42]  C. Tung,et al.  Detection of pancreatic cancer tumours and precursor lesions by cathepsin E activity in mouse models , 2011, Gut.

[43]  D. Ichikawa,et al.  Novel diagnostic value of circulating miR-18a in plasma of patients with pancreatic cancer , 2011, British Journal of Cancer.

[44]  D. Chia,et al.  Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer , 2011, Gut.

[45]  Eithne Costello,et al.  Enhancing the translation of cancer biomarkers , 2011, The British journal of surgery.

[46]  Y. Paik,et al.  Proteomic analysis of pancreatic juice for the identification of biomarkers of pancreatic cancer , 2011, Journal of Cancer Research and Clinical Oncology.

[47]  Klaus Pantel,et al.  Cell-free nucleic acids as biomarkers in cancer patients , 2011, Nature Reviews Cancer.

[48]  Shou-Jiang Tang,et al.  The Clinical Utility and Limitations of Serum Carbohydrate Antigen (CA19-9) as a Diagnostic Tool for Pancreatic Cancer and Cholangiocarcinoma , 2011, Digestive Diseases and Sciences.

[49]  William E Grizzle,et al.  Serum Biomarker Panels for the Detection of Pancreatic Cancer , 2011, Clinical Cancer Research.

[50]  L. Liotta,et al.  Circulating autoantibodies to phosphorylated α-enolase are a hallmark of pancreatic cancer. , 2011, Journal of proteome research.

[51]  Holger Sültmann,et al.  Serum microRNAs as non-invasive biomarkers for cancer , 2010, Molecular Cancer.

[52]  Nicholas F. Marko,et al.  Mathematical Modeling of Molecular Data in Translational Medicine: Theoretical Considerations , 2010, Science Translational Medicine.

[53]  Andrew Menzies,et al.  The patterns and dynamics of genomic instability in metastatic pancreatic cancer , 2010, Nature.

[54]  M. Nowak,et al.  Distant Metastasis Occurs Late during the Genetic Evolution of Pancreatic Cancer , 2010, Nature.

[55]  H. Friess,et al.  Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. , 2010, JAMA.

[56]  Kimberly Walter,et al.  Pancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levels. , 2010, Cancer research.

[57]  Ugo Boggi,et al.  MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. , 2010, Cancer research.

[58]  Quynh-Thu Le,et al.  Circulating miR-210 as a Novel Hypoxia Marker in Pancreatic Cancer. , 2010, Translational oncology.

[59]  L. Buscail,et al.  MicroRNA-21 is induced early in pancreatic ductal adenocarcinoma precursor lesions. , 2010, Clinical chemistry.

[60]  R. Hruban,et al.  Aberrant MicroRNA-155 Expression Is an Early Event in the Multistep Progression of Pancreatic Adenocarcinoma , 2010, Pancreatology.

[61]  M. Moore,et al.  Advanced pancreatic carcinoma: current treatment and future challenges , 2010, Nature Reviews Clinical Oncology.

[62]  David Elashoff,et al.  Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. , 2010, Gastroenterology.

[63]  D. Ransohoff,et al.  Sources of bias in specimens for research about molecular markers for cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[64]  W. Scheithauer,et al.  Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[65]  Eithne Costello,et al.  Pancreatic Cancer: Proteomic Approaches to a Challenging Disease , 2009, Pancreatology.

[66]  R. Weinberg,et al.  Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits , 2009, Nature Reviews Cancer.

[67]  M. Büchler,et al.  Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer: composite data from the ESPAC-1 and -3(v1) trials , 2009, British Journal of Cancer.

[68]  M. Parmar,et al.  Recruitment to multicentre trials—lessons from UKCTOCS: descriptive study , 2008, BMJ : British Medical Journal.

[69]  Lianbo Yu,et al.  Detection of microRNA Expression in Human Peripheral Blood Microvesicles , 2008, PloS one.

[70]  S. Dima,et al.  Assessment of soluble angiogenic markers in pancreatic cancer. , 2008, Biomarkers in medicine.

[71]  C. Langmead,et al.  ANGIOPOIETIN-2, A REGULATOR OF VASCULAR PERMEABILITY IN INFLAMMATION IS ELEVATED IN SEVERE ACUTE PANCREATITIS AND IS ASSOCIATED WITH SYSTEMIC ORGAN FAILURE , 2008 .

[72]  Derrick Wong,et al.  Serum CA19-9 Decline Compared to Radiographic Response as a Surrogate for Clinical Outcomes in Patients With Metastatic Pancreatic Cancer Receiving Chemotherapy , 2008, Pancreas.

[73]  N. Wilczynski Quality of reporting of diagnostic accuracy studies: no change since STARD statement publication--before-and-after study. , 2008, Radiology.

[74]  Michelle A. Anderson,et al.  A Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Development , 2008, PLoS medicine.

[75]  F. Itokawa,et al.  Detection of circulating tumor cells in patients with pancreatic cancer: a preliminary result. , 2008, Journal of hepato-biliary-pancreatic surgery.

[76]  Ananda Basu,et al.  Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. , 2008, Gastroenterology.

[77]  R. Eils,et al.  Systemic spread is an early step in breast cancer. , 2008, Cancer cell.

[78]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[79]  David F Ransohoff,et al.  How to improve reliability and efficiency of research about molecular markers: roles of phases, guidelines, and study design. , 2007, Journal of clinical epidemiology.

[80]  T. Davison,et al.  MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma , 2007, Oncogene.

[81]  J. Lötvall,et al.  Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells , 2007, Nature Cell Biology.

[82]  C. Croce,et al.  MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. , 2007, JAMA.

[83]  Thomas D. Schmittgen,et al.  Expression profiling identifies microRNA signature in pancreatic cancer , 2006, International journal of cancer.

[84]  Daniel F Hayes,et al.  ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[85]  M. Goggins,et al.  Detecting low-abundance p16 and p53 mutations in pancreatic juice using a novel assay: Heteroduplex analysis of limiting dilution PCRs , 2006, Cancer biology & therapy.

[86]  P. Bossuyt,et al.  The quality of diagnostic accuracy studies since the STARD statement , 2006, Neurology.

[87]  Fiona Campbell,et al.  Proteomic analysis of chronic pancreatitis and pancreatic adenocarcinoma. , 2005, Gastroenterology.

[88]  W. Greenhalf,et al.  Molecular analysis to detect pancreatic ductal adenocarcinoma in high-risk groups. , 2005, Gastroenterology.

[89]  Jonathan W. Uhr,et al.  Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases , 2004, Clinical Cancer Research.

[90]  Ruud H. Brakenhoff,et al.  Dissecting the metastatic cascade , 2004, Nature Reviews Cancer.

[91]  Helen Hickey,et al.  A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. , 2004, The New England journal of medicine.

[92]  J. Cameron,et al.  Diagnosing Pancreatic Cancer Using Methylation Specific PCR Analysis , 2003, Cancer biology & therapy.

[93]  N E Day,et al.  European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection , 2002, Public Health Nutrition.

[94]  C. Rosty,et al.  Early detection of pancreatic carcinoma. , 2002, Hematology/oncology clinics of North America.

[95]  D. Winchester,et al.  Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. , 1999, Journal of the American College of Surgeons.

[96]  K. Ohtsubo,et al.  Detection of mutations of p53 tumor suppressor gene in pancreatic juice and its application to diagnosis of patients with pancreatic cancer: comparison with K-ras mutation. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[97]  G. Capellá,et al.  K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: diagnostic utility and prognostic significance. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[98]  K. Lew,et al.  Characterization of monoclonal antibody PAM4 reactive with a pancreatic cancer mucin , 1994, International journal of cancer.

[99]  T. Okai,et al.  Levels of carcinoembryonic antigen and carbohydrate antigen (CA19-9) in pure pancreatic juice and sera in a patient with occult pancreatic cancer. , 1992, Journal of clinical gastroenterology.

[100]  A. Azmi,et al.  Systems biology approaches to pancreatic cancer detection, prevention and treatment. , 2014, Current pharmaceutical design.

[101]  H. Bonkovsky,et al.  Discovery of putative pancreatic cancer biomarkers using subcellular proteomics. , 2011, Journal of proteomics.

[102]  W. Greenhalf,et al.  Confounding effect of obstructive jaundice in the interpretation of proteomic plasma profiling data for pancreatic cancer. , 2009, Journal of proteome research.

[103]  D. Landsittel,et al.  Multianalyte profiling of serum cytokines for detection of pancreatic cancer. , 2005, Cancer biomarkers : section A of Disease markers.

[104]  David Moher,et al.  Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. , 2003, AJR. American journal of roentgenology.