Prognostic Value of O-GlcNAc Modification and Its Related Enzymes in Lung Adenocarcinoma
Omid Rouhi, Leonidas D Arvanitis, Kelly A Kaiser, Sanjib Basu, Brett Mahon, Mark Pool, Michael Liptay, Philip Bonomi, Jeffrey A Borgia. Rush University, Chicago, IL
Background: Post-ribosomal protein modification with an N-acetylglucosamine (O-GlcNAc) residue is functionally similar to phosphorylation and is vital to cellular regulation and homeostasis. The enzymes responsible for the addition and removal of O-GlcNAc are 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 and tumor suppressors. Here, we investigated the prognostic significance of O-GlcNAc modification components in lung adenocarcinoma.
Design: Immunohistochemical staining for O-GlcNAcylation, OGT, and OGA was performed on 65 primary lung adenocarcinoma and matching metastatic lymph nodes. 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. A score was calculated based on these parameters for statistical comparisons. We then evealuated the following parameters: differential primary tumor, adjacent normal tissue and lymph node staining; recurrence status; recurrence free and overall survival.
Results: The global O-GlcNAcylation levels in cytoplasm were significantly elevated in lung adenocarcinoma tissues (n=40) than that in healthy lung tissues (p<0.001). There was no significant difference in status of O-GlcNAcylation level and OGT expression between primary tumors with and without lymph node metastasis, however, cytoplasmic OGA was lower in lymph node positive group (p=0.033). Comparing primary tumors with their matching metastatic lymph nodes revealed that cytoplasmic level of OGlcNAcylation (p<0.001), OGT (p=0.003), and OGA (p=0.001) was overexpressed in metastatic lymph nodes. Finally, survival analysis showed that better overall and recurrence free survival was observed in patients with higher cytoplasmic O-GlcNAc modification (p<0.001, 0.024 respectively), but high nuclear OGA expression in primary tumors was correlated with lower recurrence free survival and overall survival (p=0.039, <0.001 respectively).
Conclusions: 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.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 308, Wednesday Morning