Abstract 935: Lung cancer metabolomics identifies metabolites as robust risk biomarkers
Authors: Haznadar Majda , Cai Qiuyin , Krausz Kristopher W. , Bowman Elise D. , Blot William J. , Gonzalez Frank J. , Harris Curtis C. 
Published: August 2015

Lung cancer is a major health burden on the general population, as it will kill 160,000 people annually in the US, making it the number one cause of cancer related deaths. The prognosis for lung cancer is still very poor, with fewer than 15% of patients surviving 5 years after primary diagnosis, indicating the enormous necessity to search for biomarkers for early lung cancer detection when amenable to treatment. Currently accepted methods for early detection of lung cancer are limited to low-dose spiral CT (LDCT) scanning in high-risk populations. However, the specificity of LDCT is low, with a false positive rate of 96%. Our goal is to identify stable and reproducible biomarkers in non-invasively collected biofluids, namely urine, that may be powerful risk assessment screening tools. To that extent, we first conducted a first of its kind effort using mass spectrometry-based untargeted metabolic profiling of urine samples from 469 lung cancer patients and 536 healthy population controls in the NCI-MD case-control study, We found four metabolites to be independent and robust classifiers of lung cancer diagnosis and prognosis: novel and previously un-described creatine riboside, N-acetylneuraminic acid (NANA), cortisol sulfate and a metabolite with a mass to charge ratio of 561 detected in electrospray ionization (ESI) positive mode. Furthermore, creatine riboside and NANA were also found to be elevated in 48 stage I lung tumors matched to adjacent non-tumor tissues, linking them directly to deregulated tumor metabolism. The next step was to assess whether these metabolites are elevated in subjects prior to lung cancer diagnosis. To that end, we analyzed the urine of 180 patients and 349 non-diseased controls from the prospective Southern Community Cohort Study (SCCS). Controls were individually matched to cases in a 2:1 ratio using incidence density sampling by age (+/- 2 years), sex, race, recruitment site, menopausal status (women), and date of sample collection (+/- 6 months). We confirmed that two of the four metabolites, creatine riboside and NANA were associated with lung cancer risk with smoking-adjusted Odds Ratios (OR) of 1.8 and 1.5, respectively (P &lt;0.02). These metabolites, having been observed as deregulated in tumor metabolism, may become interesting targets for future studies regarding therapeutic interventions. The associations with risk were stronger among European than African Americans, and among whites were observed in individuals having been diagnosed within two years of cohort enrollment (OR = 2.7 and 2.5, respectively, for creatine riboside and NANA; P = 0.004) and two or more years after cohort enrollment (OR = 3.6 and 3.3, respectively; P = 0.02). These results provide strong preliminary data that identified metabolite biomarkers have a potential utility as clinical screening tools for early diagnosis of lung cancer, when prognosis is significantly better.

Citation Format: Majda Haznadar, Qiuyin Cai, Kristopher W. Krausz, Elise D. Bowman, William J. Blot, Frank J. Gonzalez, Curtis C. Harris. Lung cancer metabolomics identifies metabolites as robust risk biomarkers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 935. doi:10.1158/1538-7445.AM2015-935