Abstract 4792: Biomarker discovery: Correlation of peripheral and tumoral markers in matched tumor and plasma samples
Authors: Mulen Marika , Soukharev Serguei , Czapiga Meggan , Richman Laura , LaVallee Theresa , Robbins Paul B. 
Published: August 2012

The heterogeneous nature of cancer necessitates the identification of markers to enable selection of appropriate patients for treatment and maximal clinical benefit. Archival tumor specimens are often analyzed for biomarkers, but may not reflect a patient's current state of disease. Predictive biomarkers from matrices amenable to longitudinal analyses and available through minimally invasive approaches could greatly improve patient outcomes by ensuring that the right patient receives the right drug. Peripheral markers are accessible and attractive, however, their relationship to tumoral markers, tumor biology as well as to primary or secondary clinical outcomes are not well understood. We examined the correlations among potential predictive biomarkers in these compartments by performing proteomic profiling of ∼300 analytes in 100 matched plasma and tumor tissue samples derived from patients with colorectal cancer (CRC), gastric, ovarian, and non-small cell lung cancer (NSCLC) of squamous cell carcinoma (SCC) or adenocarcinoma (ADC) histology. Using Luminex based assays, we identified markers which clearly distinguish each tumor type from another and may be useful for patient enrichment. VEGF has been implicated in processes essential to tumor growth and disease progression such as angiogenesis, vasculogenesis and hypoxia. Therefore, we examined the relationship between VEGF levels in plasma samples and tumor tissue within individual patients and explored the correlations among VEGF levels with those of other soluble proteins in the same matrices as well as with a marker of blood vessel formation in the tumors, microvessel density (MVD). We found the highest level of VEGF in the plasma of CRC patients but NSCLC patients displayed the highest level of VEGF in tumors. A poor correlation between tumoral or plasma VEGF levels was observed in all of the samples except for those from NSCLC SCC patients. MVD analysis of the tumors revealed that gastric and NSCLC ADC patients have a higher density of capillary vessels than other cancers. Surprisingly, no intra-patient correlation was detected between tumoral levels or plasma levels of VEGF and MVD. However, modest correlations between the MVD level in tumor tissues and select analytes in plasma have been observed for some tumor types. Further evaluation of these potential protein signatures in additional matched patient samples and animal disease models is warranted to generate clinically testable hypotheses for patient enrichment. The validity of these protein signatures as predictive markers for response to targeted therapies must be tested clinically. These novel and unexpected findings suggest that some peripheral markers may accurately represent the biology of the tumor and that matched sample analysis can provide an approach for biomarker discovery and hypothesis generation.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4792. doi:1538-7445.AM2012-4792