Published in: Journal of Clinical Oncology, Volume 35, no. 15_suppl., 30 May 2017

Authors

Vincenzo Lagani, Ioannis Tsamardinos

Oluf D. Røe, Hans Fredrik Kvitvang, Maria Markaki, Robin Mjelle

Abstract

Background:
The Cancer-Biomarkers in HUNTinitiative seek to identify novel biomarkers for the early cancer diagnosis. For lung cancers and mesothelioma clinically useful, early markers are not available. In the prospective HUNT study in Norway, pre-diagnostic samples ranging from 0-20 years before diagnosis are available for research purposes. Here we present our first results on high-throughput metabolomics analysis in serum two months to 16 years before diagnosis.

Methods:
LC-MS untargeted (Amide-) metabolites (n = 1042) were profiled in serum samples from 48 future patients (12 each of adeno-, squamous cell carcinoma, small-cell lung cancer, and mesothelioma) and from 48 controls that were cancer-free 5 years after blood sampling. All were active smokers. Metabolic features for (a) each cancer and (b) all cancers pooled together were analyzed with moderated t-test (R limma package). Multivariate analyses included (a) OPLS-DA and (b) signature identification through a data-analysis pipeline that includes feature selection (such as the algorithm in [1]), non-linear modelers (e.g., Random Forests), and Cross-Validation with bootstrapping [2] for optimizing algorithms and providing unbiased performance estimation. The pipeline is implemented in the Just Add Data software (Gnosis Data Analysis).

Results:
Univariate and OPLS-DA analyses did not identify any association between metabolites and cancer. The non-linear data analysis pipeline identified a signature containing five metabolites able to discriminate between cancer and non-cancer patients, statistically significantly better than random (AUC = 0.667, CI = [0.536, 0.784]).

Conclusions:
Our results indicate that metabolic profiling in serum may help in identifying subjects who are likely to be diagnosed with lung cancer/mesothelioma in a time period of several years before diagnosis. More data will be presented at the annual meeting. Further validation studies are planned for confirming the replicability of these findings. 1) Lagani V et al., 2016. arXiv:1611.03227 2) Greasidou L, 2017. Bias Correction of the Cross-Validation Performance Estimate and Speed Up of its Execution Time, MSc Thesis, University of Crete