Abstract
Abstract Background: O-GlcNAcylation, post-ribosomal protein modification with an N-acetylglucosamine (O-GlcNAc) residue is functionally similar to phosphorylation in cellular physiology in that it is vital to cellular regulation and homeostasis. The enzymes responsible for the addition and removal of O-GlcNAc have been identified as O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). It has been proposed that O-GlcNAcylation may be an important regulator of cancer initiation and progression, based on the O-GlcNAcylation of many oncogenes/ proto-oncolgenes and tumor suppressors, but with few citations in the literature on the subject. Here, we investigated the correlation of O-GlcNAc modification components with expression of Epithelial-Mesenchymal-Transition (EMT)/Stem cell markers in 65 cases of lung adenocarcinoma. Methods: Immunohistochemical staining for O-GlcNAcylation, OGT, OGA, E-cadherin, vimentin, CD133, CD34 and CXCR-4 were performed on 65 primary lung adenocarcinoma and matching metastatic lymph nodes. All patients were treated by complete anatomic resections and limited to T1-2N0-2M0 (pathological). Scoring was accomplished by evaluating localization (membrane, cytoplasm, peri-nuclear, and nuclear), stain intensity (0: no staining, 1: weak staining, 2: strong staining) and frequency for at least 200 cells per field (400X magnification), with 25 random fields surveyed per section. This was done by two readers, and a score was then calculated based on these parameters for statistical comparisons (0: lowest, 2: highest). We then evealuated the correlation of these markers with each other through Pearson's correlation in SPSS v18.0. Results: Higher expression of cytoplasmic OGT was correlated with higher cytoplasmic OGlcNAcylation in primary tumor (r=0.40, p=0.001) and lymph node metastasis (r=0.567, p=0.001). However, we did not observe any relationship between OGA and OGlcNAcylation level. Vimentin showed positive correlation with nuclear OGlcNAcylation in both primary (r=0.281, p=0.031) and lymph node (r=0.380, p=0.035). but no relationship was observed with cytoplasmic OGlcNacylation. Also, CD133 demontrated positive correlation with cytoplasmic OGT in both primary (r=0.510, p=<0.001) and lymph node (r=0.555, p=0.001). Conclusion: Our results suggest that O-GlcNAcylation might play important roles in lung adenocarcinoma initiation and progression and may be a potential prognostic factor to predict patient risk of recurrence after surgery. Also, these findings may provide us with added insights regarding the mechanism of metastasis, although, further investigations are warranted to validate our results. 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 2404. doi:1538-7445.AM2012-2404
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