Noncoding RNA Biomarkers for Noninvasive and Early Detection of Pancreatic Cancer

Information

  • Research Project
  • 9553699
  • ApplicationId
    9553699
  • Core Project Number
    U01CA214254
  • Full Project Number
    5U01CA214254-02
  • Serial Number
    214254
  • FOA Number
    PAR-15-289
  • Sub Project Id
  • Project Start Date
    9/1/2017 - 6 years ago
  • Project End Date
    7/31/2022 - a year ago
  • Program Officer Name
    GHOSH-JANJIGIAN, SHARMISTHA
  • Budget Start Date
    8/1/2018 - 5 years ago
  • Budget End Date
    7/31/2019 - 4 years ago
  • Fiscal Year
    2018
  • Support Year
    02
  • Suffix
  • Award Notice Date
    8/2/2018 - 5 years ago

Noncoding RNA Biomarkers for Noninvasive and Early Detection of Pancreatic Cancer

PROJECT SUMMARY: Pancreatic cancer is the fourth leading cause of adult cancer deaths in the U.S., and will become the second leading cause of cancer-related deaths by 2030. The lack of reliable and cost-effective assays impedes wide-spread pancreatic cancer diagnostics. Clearly, early diagnostic procedures will improve the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC), but will require novel methods of development. MicroRNAs (miRNAs) are small noncoding RNAs that are implicated in the tumorigenesis of every human cancer, including PDAC. Importantly, miRNAs are robust and resistant to degradation in tissues and body fluids, making them ideal candidates as non-invasive biomarkers. The recent discovery of cancers that actively excrete specific miRNAs in small vesicles, called ?exosomes?, has brought additional enthusiasm to the cancer biomarker arena. Previous attempts to define blood-based miRNA biomarkers that can discriminate between non-invasive, early-stage and late-stage PDAC were insufficiently sensitive or specific because of improperly designed cohorts and the narrow dynamic ranges of technologies used. Furthermore, candidate markers were non-comprehensively selected, studies lacked important controls, and the cohorts were insufficiently powered or validated, or did not represent the average risk population. These factors stifled the discovery of miRNA biomarkers that could identify asymptomatic patients before metastatic disease had developed, or distinguish early stage, radiographically occult PDAC from noninvasive pancreatic precancerous neoplasms (PNs). In this proposal, innovative strategies including Next Generation Sequencing (NGS)-based miRNA-Seq will be applied to the genome-wide and systematic discovery of comprehensive and highly specific blood-based miRNAs by analyzing tissues and matching plasma that discern different stages of invasive PDAC and PN. A novel and powerful new approach is being proposed to identify biomarkers with the highest sensitivity and specificity, which will be validated in a prospective, large, well-characterized samples through the following Specific Aims. Aim #1: Discover candidate cell-free and exosomal-miRNA biomarkers using small RNA-Seq in matched tissue and plasma from patients with PDAC, PNs, pancreatitis and normal pancreas. Aim #2: Develop a cell-free and exosomal-miRNA biomarker panel that distinguishes patients with PDAC from those with PNs or pancreatitis. Aim #3: Clinically validate the optimized panel of non-invasive miRNA biomarkers (identified in Aim #2) in prospective cohorts of patients with PDAC and PNs. This project is innovative as it will use NGS-based miRNA-Sequencing for discovery of cell-free and exosomal miRNA biomarkers in matched tissue and plasma samples, and validate these in multiple, well-characterized cohorts of patients with PNs and PDAC vs. controls. If successful, this proposal will profoundly transform early- detection of pancreatic cancer using a non-invasive, robust and inexpensive clinical assay.

IC Name
NATIONAL CANCER INSTITUTE
  • Activity
    U01
  • Administering IC
    CA
  • Application Type
    5
  • Direct Cost Amount
    761686
  • Indirect Cost Amount
    258538
  • Total Cost
    1020224
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    393
  • Ed Inst. Type
  • Funding ICs
    NCI:1020224\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZCA1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    BAYLOR RESEARCH INSTITUTE
  • Organization Department
  • Organization DUNS
    145745022
  • Organization City
    DALLAS
  • Organization State
    TX
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    75201
  • Organization District
    UNITED STATES