Abstract

Abstract Lung cancer is the leading cause of cancer-related moralities in the US and worldwide. Non small cell lung cancer (NSCLC) accounts for 80 % of all diagnosed lung cancer cases. The lack of reliable, non-invasive diagnostic tests prompted the search for viable diagnostic protein markers. We report here the identification and validation of galectin7 as a novel blood-based biomarker for diagnosis of NSCLC. To identify potential blood protein markers that could be used for diagnosis of NSCLC, we implemented a multiphase validation scheme exploiting a large pool of novel protein markers shown to be over expressed in NSCLC tissues by our group by shotgun- mass spectrometry. Top candidates were first selected using bioinformatics tools including Ingenuity Pathway Analysis (IPA), Web gestalt and DAVID by applying a combination of statistical and biological filters including expression levels in cancer tissues, reported presence in plasma and other biofluids, and statistical significance. The resulting list of candidates was further refined by cross examination against other publically available data bases such as Plasma Proteome project of the Human Proteome Organization (PPP-HUPO) and Oncomine. We decided to focus our efforts on galectin 7, one of our top candidates that has not been reported previously as a biomarker for lung cancer. A case-control pilot study was designed to evaluate the relative levels of galectin 7 in plasma samples of peripheral blood from a small cohort of 30 NSCLC and 15 control nonmalignant lung disease patients using ELISAs. The results of this study were subjected to a second round of validation in an independent set of plasma samples from controls and NSCLC patients. Finally, we verified the identity of our protein candidates by means of immunoprecipitation (IP) and Western blot analyses. Statistical analysis of our ELISA data on galectin7 using the Wilcoxon cox nonparametric test revealed that galectin7 was detected at significantly higher levels in NSCLC patient plasma compared to controls. To further validate our findings, a second round of interrogation was performed using a separate sample set of 30 plasma samples and their matched tissues from nonmalignant and NSCLC patients. To verify the identity of our protein markers detected by ELISA, we successfully detected galectin 7 from both tissue lysates and plasma from NSCLC patients by Western blot analysis. Based on our preliminary results, we believe that we present the first evidence that galcetin 7 is a potential diagnostic blood-based biomarker for NSCLC. Retrospective clinical studies are currently underway to test the utility of galectin7 for diagnosis of early stage NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4157. doi:10.1158/1538-7445.AM2011-4157

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