7662 Background: Epigenetic modifications, such as methylation and/or acetylation of histones, may contribute to the development and progression of cancer. We investigated whether histone modifications influence prognosis of non-small cell lung cancer (NSCLC). Methods: We used immunohistochemistry to assess histone 3 lysine 4 dimethylation (H3K4diMe), and acetylation of histone 2A lysine 5 (H2AK5Ac), histone 2B lysine 12 (H2BK12Ac), histone 3 lysine 9 (H3K9Ac), and histone 4 lysine 8 (H4K8Ac), in resected tumor samples of 138 NSCLC patients. In addition, the genotype of a tandem repeat polymorphism in the histone 3 methyltransferase SMYD3 gene was determined using PCR and capillary electrophoresis. Data were analyzed using a recursive partitioning analysis (RPA). Results: The overall median expression of H3K4diMe, H2AK5Ac, H2BK12Ac, H3K9Ac, and H4K8Ac were 75, 10, 0, 25, and 80%, respectively. The RPA classified the patients into seven distinct prognostic groups based on TNM stage (first node), histology (second node) and histone modifications (third node). H3K4diMe (< or =85% tumor cells), H3K9Ac (< or =68% tumor cells) and H2AKAc (< or =5% tumor cells) were retained by RPA. The SMYD3 genotype was not retained by RPA. The seven groups were associated with significantly different disease- free (p<0.0001) and overall survival (p<0.0001). Interestingly, the four groups determined by stage I patients (below the first node) displayed dramatic differences in survival (median from 10 months in adenocarcinoma, H3K9Ac=68%, to 147 months in non-adenocarcinoma, H3K4diMe=85%). Conclusions: The prognostic influence of global histone modifications is greater in early stage NSCLC and it may help in the selection of early stage NSCLC patients for adjuvant treatment and provides a rationale for the use of combination of standard chemotherapy with drugs interacting with histone modifications such as histone deacetylases (HDAC) inhibitors. No significant financial relationships to disclose.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.