Abstract 210: Development of scores reflective of biological processes underlying human disease states from mass spectrometry of serum
Authors: Oliveira Carlos , Grigorieva Julia , Meyer Krista D. , Roder Joanna , Roder Heinrich 
Published: July 2017

Abstract
A method was developed that allows the evaluation of complex biological processes from mass spectrometry of human serum samples. Applying gene set enrichment analysis ideas to matched protein expression data from a panel of 1129 proteins and deep MALDI® mass spectral data from a set of 49 human serum samples with lung cancer (n=45) or non-cancer (n=4), subsets of mass spectral features associated with selected biological functions were identified. Biological functions included acute response, complement system, and wound healing and the protein members of each function were assigned using the intersection of gene ontologies and the protein panel. Using mass spectral data collected from an independent NSCLC sample cohort (n=85) from patients treated with targeted therapy, principal component analysis was used to derive scoring functions (combinations of the feature subsets) for each biological class. These scoring functions were validated in an additional NSCLC sample set (n=123) treated with chemotherapy. The scoring functions can be applied to mass spectra obtained from any human serum sample to generate scores associated with individual biological processes. We have developed scoring functions for several biological processes. Acute response score was associated with outcome in Cox proportional hazard analysis in several independent patient cohorts across multiple therapies and indications, including lung cancer, as mentioned, and ovarian cancer (n=165) treated with platinum doublets following surgery. Choice of a single cutoff allowed stratification of patients into groups with significantly better or worse outcome. In a cohort of nivolumab treated NSCLC patients (n=67) with available longitudinal samples, outcome was also found to depend on changes in scores during therapy. Interestingly, while the distributions of acute phase scores were quite similar across multiple tumor types, scores for other biological functions, such as wound healing, varied considerably. This may reflect differences in relative importance of individual biological functions between tumor types. A scoring system based on biological functional categories has a wide range of uses that could be tested and applied in a clinical setting. Currently, tests that measure a single biomarker for monitoring a particular disease have questionable utility and limit the usefulness to the clinician and patient treatment decision making. A tool that measures the activity of a complex biological process could be useful in deciding when an intervention is needed (screening), or for monitoring the effects during therapy.
Citation Format: Carlos Oliveira, Julia Grigorieva, Krista D. Meyer, Joanna Roder, Heinrich Roder. Development of scores reflective of biological processes underlying human disease states from mass spectrometry of serum [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 210. doi:10.1158/1538-7445.AM2017-210