Jiaqi Huang

Ph.D

NIH

Postdoc fellow

PLCO (Learn more about this study)

2017-1017

Oct 23, 2018

Serum Metabolomic Profiling of Glioma Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

In an effort to discover altered metabolites or biochemical pathways relevant to cancer etiology, early detection, and potential prevention, we have conducted several prospective serum metabolomics analyses that have successfully identified cancer-metabolite associations up to 25 years prior to diagnosis. Malignancies with few established and preventable causal factors represent prime targets for such agnostic, broad-spectrum approaches to discovery and elucidation. Brain cancer is a relatively uncommon malignancy in adults - approximately 15,000 cases in the U.S. annually - but it is nearly uniformly fatal with serious morbidity. Only radiation exposure, family history, rare genetic disorders such as the Li-Fraumeni syndrome, and some evidence of inverse association with asthma and allergies have been associated with brain cancer risk. Gliomas, including glioblastoma multiforme, are the most common histological types, and there are currently no early detection tests for these malignancies.
Rapid development of technologies in liquid and gas chromatography, mass spectrometry and nuclear magnetic resonance have enabled measurement of a broad-spectrum array of low molecular weight metabolites in biofluids such as plasma and serum. Extensive prior work by our group finds that metabolomics is a reliable and robust tool to portray individual metabolomic profiling, and it has potential power as the agnostic approach to discover metabolic biomarkers relevant to disease etiology and early detection. Our previous prospective metabolomic profile of glioma identified the amino acids 2-oxoarginine, cysteine and argininate, energy metabolite alpha-ketoglutarate, and secondary bile acid chenodeoxycholate, and some other compounds, as being lower in circulation of glioma cases years in advance of diagnosis compared to study-based controls (Huang J. et al. Oncotarget, 2017). By contrast, we found several xanthine metabolites of caffeine to be related to higher disease risk. This study was conducted in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort 50-69 year old Finnish male smokers.
The present proposal would pursue a similar nested case-control investigation in the PLCO cohort aimed at reevaluation of the prior metabolite associations and determining whether other novel metabolites can be detected in this study population that will include women and nonsmokers. Meta-analysis of the ATBC and PLCO study data will enhance our statistical power. This proposed investigation will improve our understanding of biochemical basis, biologic pathways and underlying mechanisms involved in the etiology of glioma. It will advance the field by revealing unknown metabolites corresponding to the etiology, early detection of glioma, and will facilitate discovery of molecular pathways for future glioma prevention intervention and glioma risk prediction.