AS536 - Targeted serum metabolites profiling in early detection of pancreatic cancer

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Investigator Names and Contact Information

Li Jiao [jiao@bcm.edu]

Introduction/Intent

We propose to identify serum metabolic biomarkers for pancreatic cancer early diagnosis. Our goal is to identify 10-20 candidate metabolites from 500 well-characterized metabolites involved in cellular metabolism. We will validate these biomarkers in a future independent study. We have identified 47 blood samples that were collected no more than one year before the diagnosis of pancreatic cancer in the entire WHI cohort except for the active diet modification trial. We hypothesize that a targeted metabolomics discovery platform will yield a panel of biomarkers (10-20) in near-diagnostic serum that can 1) distinguish patients with pancreatic cancer from non-cancer controls; and 2) the candidate 10-20 metabolites in non-cancer controls are stable across the blood collection period (three-year interval). The performance of the identified metabolites in pancreatic cancer diagnosis will be evaluated. The sample identification and aliquot will be performed at the WHI-CCC and the metabolomics research will be conducted at the Metabolomics core facility at Baylor College of Medicine (BCM). We require no more than 200 µl unthawed serum for this study. 

Specific Aims

The major aim of this feasibility is to identify 10-20 candidate metabolites for early diagnosis of pancreatic cancer using targeted profiling of 500 metabolites in pre-diagnostic sera of 47 cases and individually matched 47 healthy controls using Liquid Chromatography/Mass Spectroscopy (LC/MS).

Specific aim 1: To identify pancreatic cancer-specific markers in 47 cases and 47 controls using the unbiased targeted approach with a two-phase design.

   Specific aim 1.1: To assemble the list of the target metabolites and develop the assay for all metabolites. 

Specific aim 1.2: To perform a targeted metabolomics investigation on 500 metabolites among 30 cases and 30 individually matched controls and identify 10-20 metabolites as pancreatic cancer-specific markers (the training set).    

Specific aim 1.3: To perform the internal validation research on 10-20 metabolites among 17 cases and 17 individually matched controls (the validation set).

Specific aim 2: To compare the profile of 10-20 metabolites using repeatedly collected samples (3-year apart) from 47 controls in order to examine the intra-individual variation of the identified metabolites.