Validation of Useful Markers Generated by Next Generation Bio-data Based Genome Research and Cohort Study
Condition: BCL2 Gene mRNA Overexpression
Study type: Observational

Summary: 
      Multiple biomarker development through validation of useful markers generated by next
      generation bio-data based genome research and cohort study
    

Detailed description: 
      1. Objectives The study will be performed to develop the integrated analytical methods of
           genomic data and clinical data and the bio-control network analysis, through which
           knowledge-based integrated analysis system can be developed and then biomarker for early
           diagnosis and treatment of pancreatic cancer and bile duct cancer, and finally the
           customized disease management system. Also, it is to confirm the effectiveness of
           diagnostic chip for research purpose by applying pancreatic/bile duct cancer-specific
           biomarker, miRNA, found through the integrated analysis of genomic data and clinical
           data of patients with pancreatic/bile duct cancer to the blood of patients with
           pancreatic/bile duct cancer.

        2. Effective evaluation method

      The discrimination and calibration for algorithm through the diagnostic chip of each cancer
      type will all be examined using 10-fold cross-validation (100 repetitions). In the 10-fold
      cross-validation, the data is randomly divided into 10 same sized data, among which 9 are
      used in making a model for training and the remaining 1 is applied for test, and this process
      is randomly and independently repeated for 100 times.

      The 10-fold cross-validated AUC is calculated to see the discrimination of diagnostic chip of
      each cancer type, and the 95% confidence interval is presented by non-parametric method.

      The 10-fold cross-validated calibration plot is presented to see the calibration of
      diagnostic chip of each cancer type. The calibration plot visually demonstrate the degree of
      prediction by comparing the prediction probability of each group and the ratio of actual
      cancer patients after listing the prediction probability in the order and dividing it with
      regular intervals.

      Then, for the same subjects, the AUC of the CA 19-9, the existing cancer diagnostic tool, is
      calculated and the 95% confidence interval is presented. To compare the diagnostic chip of
      each cancer type and the AUC of CA 19-9, p-value is calculated by non-parametric method of
      10-fold cross-validated AUC.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        The number of target subjects and calculation basis for blood samples used in the
        development of multiple biomarker and diagnostic chip production are as below.

        Number of study subjects: 232 patients (pancreatic cancer 88, bile duct cancer 101, stomach
        cancer 9, colon cancer 5, normal group 29)
      
Biospecimen description: 
      Among patients with pancreatic cancer or bile duct cancer without previous chemotherapy or
      radiation therapy, the subjects are divided into operable patients and inoperable patients.

      For operable patients, about 10cc (paxgene tube) of blood sample is collected before
      operation. After operation, 400mg of cancerous tissue and 400mg of normal tissue are
      requested and received from the gene bank of Severance Hospital where the tissues are stored.
    
Keywords: biomarker; pancreatic cancer; bile duct cancer; miRNA