Multiplexed Serum Biomarkers for Pancreatic Cancer

Summary

Principal Investigator: Anna Lokshin
Abstract: Pancreatic cancer is the fifth leading cause of cancer death in the USA. This is due, in part, to the lack of early detection methods for this particularly aggressive form of cancer. None of the biomarkers of pancreatic cancer that have been identified to date are sufficiently predictive to be useful as a diagnostic or screening test. We hypothesize that a multi-marker panel will have high sensitivity and specificity for early detection of pancreatic cancer. We propose to use novel Luminex LabMAP technology that allows for simultaneous evaluation of multiple (up to 100) biomarkers in one sample. Our preliminary results suggest that our Luminex panel has significant predictive power. Our goal is to develop a reliable serum-based assay for early detection of pancreatic cancer based on the longitudinal patterns of multiple biomarkers. This project is firmly based on biomarker discoveries and strong preliminary data developed and include a team of basic cancer researchers and clinicians supported by faculty with requisite expertise in biostatistics/bioinformatics. Our immediate objectives are (i) to further expand our pancreatic cancer panel with additional pancreatic cancer-relevant biomarkers including circulating antibodies and (ii) to interpret the panel longitudinally and validate the resultant assay for patient use. To accomplish these objectives the following Specific Aims are proposed: 1. Generate and optimize a comprehensive multiplexed assay for detection of highly relevant pancreatic cancer markers. Luminex-based assay will be developed for multiplex analysis of most of the known pancreatic cancer serological biomarkers including cytokines, chemokines, angiogenic and growth factors and their receptors, as well as circulating antibodies against pancreatic antigens. 2. Use Luminex-based biomarker panels identified to select a combined multimarker panel that distinguishes patients with pancreatic cancer from healthy controls or patients with benign disease (Phase 2 validation study). Performance characteristics of biomarker panels developed in Aim I will be evaluated in a definitive cohort with adenocarcinoma of the pancreas, chronic pancreatitis, acute pancreatitis, and patients with other peri-ampullary tumors and age-, sex- and smoking status-matched healthy controls. A combination of markers allowing distinguishing patients with pancreatic cancer from those without cancer or with benign disease will be selected. The cancer-specificity of this panel will be assessed. An optimized statistical model for analyzing and combining multimarker panels will be developed. 3. Validate/optimize this multimarker panel in retrospective longitudinal study (Phases 3-4 validation study). Diagnostic utility of the multimarker assay in a general population will be validated in available prospective studies. At the conclusion of this study, we expect to develop strategies for the early detection of pancreatic cancer that are practical and efficient and can be projected to offer the best opportunity to reduce the mortality from this disease. This research study will be conducted in the context of UPCI EDRN/BDL directed by Dr. Anna Lokshin, who brings extensive experience in cancer biomarkers and Luminex multiplexed technology research. The combined team comprises an outstanding and productive group of clinical and translational cancer researchers focused on cancer biomarkers discovery, evaluation, and validation. These efforts will strongly support the research and clinical goals of the EDRN.
Funding Period: 2005-09-12 - 2010-06-30
more information: NIH RePORT

Top Publications

  1. pmc Biomarker testing for ovarian cancer: clinical utility of multiplex assays
    Brian M Nolen
    University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Avenue 1 18, Pittsburgh, PA 15213, USA
    Mol Diagn Ther 17:139-46. 2013
  2. pmc An extensive targeted proteomic analysis of disease-related protein biomarkers in urine from healthy donors
    Brian M Nolen
    University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 8:e63368. 2013
  3. pmc Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin
    Zoya Yurkovetsky
    University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Ave, Pittsburgh, PA 15213, USA
    Gynecol Oncol 107:58-65. 2007
  4. pmc A serum based analysis of ovarian epithelial tumorigenesis
    Brian Nolen
    University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA
    Gynecol Oncol 112:47-54. 2009
  5. pmc Aberrant tumor-associated antigen autoantibody profiles in healthy controls detected by multiplex bead-based immunoassay
    Brian Nolen
    University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Avenue 1 18, Pittsburgh, PA 15213, USA
    J Immunol Methods 344:116-20. 2009
  6. pmc Role of eotaxin-1 signaling in ovarian cancer
    Vera Levina
    University of Pittsburgh Cancer Institute, Department of Medicine, Pittsburgh, Pennsylvania 15213, USA
    Clin Cancer Res 15:2647-56. 2009
  7. pmc Biological significance of prolactin in gynecologic cancers
    Vera V Levina
    University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
    Cancer Res 69:5226-33. 2009
  8. pmc Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms
    Brian B Haab
    Van Andel Research Institute, Grand Rapids, MI, USA
    Ann Surg 251:937-45. 2010
  9. pmc Serum biomarker panels for the detection of pancreatic cancer
    Randall E Brand
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Clin Cancer Res 17:805-16. 2011

Scientific Experts

  • Brian M Nolen
  • Anna E Lokshin
  • Elieser Gorelik
  • Randall E Brand
  • Brian B Haab
  • Miroslaw J Szczepanski
  • Marta E Szajnik
  • Vera Levina
  • Vera V Levina
  • Zoya Yurkovetsky
  • Mohamad A Eloubeidi
  • Juan P Arnoletti
  • William E Grizzle
  • Michael Goldberg
  • Christopher J Langmead
  • David C Whitcomb
  • Douglas P Landsittel
  • Peter J Allen
  • Eric Elton
  • Selwyn M Vickers
  • John D Christein
  • Herbert J Zeh
  • Tingting Yue
  • Lin Li
  • Diane M Simeone
  • Ziding Feng
  • C Max Schmidt
  • Andrew Porter
  • Michelle A Anderson
  • James Scheiman
  • Dawn Barnes
  • Gil Mor
  • Jinsong Liu
  • Jeffrey R Marks
  • Yunyun Su
  • Ronald B Herberman
  • Andrew K Godwin
  • Peng Cheng
  • David Fishman
  • Adele M Marrangoni
  • Larry G Maxwell
  • Steve Skates
  • Lyudmila Velikokhatnaya
  • G Larry Maxwell
  • Matthew Winans
  • Shlomo Ta'asan
  • Anna Lokshin
  • Faina Linkov
  • Aleksey Lomakin
  • Adele Marrangoni
  • Alex Rand
  • Karen Lu

Detail Information

Publications9

  1. pmc Biomarker testing for ovarian cancer: clinical utility of multiplex assays
    Brian M Nolen
    University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Avenue 1 18, Pittsburgh, PA 15213, USA
    Mol Diagn Ther 17:139-46. 2013
    ..Thus while effective routine screening for ovarian cancer remains a lofty goal, advancement within the clinical management of pelvic mass diagnoses appears to be near at hand...
  2. pmc An extensive targeted proteomic analysis of disease-related protein biomarkers in urine from healthy donors
    Brian M Nolen
    University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 8:e63368. 2013
    ....
  3. pmc Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin
    Zoya Yurkovetsky
    University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Ave, Pittsburgh, PA 15213, USA
    Gynecol Oncol 107:58-65. 2007
    ..Therefore, prevention and early detection may further reduce the burden of this challenging disease...
  4. pmc A serum based analysis of ovarian epithelial tumorigenesis
    Brian Nolen
    University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA
    Gynecol Oncol 112:47-54. 2009
    ....
  5. pmc Aberrant tumor-associated antigen autoantibody profiles in healthy controls detected by multiplex bead-based immunoassay
    Brian Nolen
    University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Avenue 1 18, Pittsburgh, PA 15213, USA
    J Immunol Methods 344:116-20. 2009
    ..Such factors will require further characterization and the development of adequate controls in order to improve the performance of diagnostic tests...
  6. pmc Role of eotaxin-1 signaling in ovarian cancer
    Vera Levina
    University of Pittsburgh Cancer Institute, Department of Medicine, Pittsburgh, Pennsylvania 15213, USA
    Clin Cancer Res 15:2647-56. 2009
    ..Tumor cell growth and migration can be directly regulated by chemokines. In the present study, the association of CCL11 with ovarian cancer has been investigated...
  7. pmc Biological significance of prolactin in gynecologic cancers
    Vera V Levina
    University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
    Cancer Res 69:5226-33. 2009
    ..In summary, we present findings that indicate an important role for PRL in ovarian and endometrial tumorigenesis. PRL may represent a risk factor for ovarian and endometrial cancers...
  8. pmc Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms
    Brian B Haab
    Van Andel Research Institute, Grand Rapids, MI, USA
    Ann Surg 251:937-45. 2010
    ..Here we explored whether glycosylation variants on specific proteins in cyst fluid samples could serve as biomarkers to aid in this diagnosis...
  9. pmc Serum biomarker panels for the detection of pancreatic cancer
    Randall E Brand
    Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Clin Cancer Res 17:805-16. 2011
    ..Serum-biomarker based screening for pancreatic cancer could greatly improve survival in appropriately targeted high-risk populations...