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• W2947194687 abstract "6050 Background: CTGF plays a central role in tissue remodeling and has emerged as an attractive novel therapeutic target. We sought to investigate the impact of CTGF methylation status (CTGF-M) in predicting outcome of HNSCC patients undergoing RCHT. Methods: CTGF-M was discovered by applying Illumina 450K/850K arrays to DNA extracted from FFPE material of patients homogeneously treated with surgery followed by adjuvant cisplatin-based RCHT in frame of the DKTK-ROG multicenter retrospective trial (n = 194, training cohort). Methylation probes correlating with overall survival (OS) and progression were identified using random forest. Validation was done in 4 cohorts including DKTK-ROG definitive RCHT (n = 110) and 3 RCHT cohorts from Heidelberg, Dresden and Munich (n = 222). CTGF-M and RNAseq data from The Cancer Genome Atlas (TCGA) (n = 206) were analyzed to identify differentially expressed genes (DEG) as a function of CTGF-M. Results: Increased methylation of 2 probes (mapping to CTGF 3’UTR and gene body) was associated with significantly improved OS in the training cohort (HR = 0.51, p = 0.044) and the validation cohort (HR = 0.67, p = 0.016), in multivariate cox regressions adjusting for HPV status, age, T and N stages, location and treatment (adjuvant vs definitive RCHT). In the TCGA, probes’ methylation was significantly inversely correlated with CTGF gene expression (r = -0.18 and -0.51, p < 0.05). 1843 DEGs were found at FDR < 0.05 as a function of CTGF-M. Pathways mapping to tissue remodeling were significantly enriched for among downregulated genes in CTGF hypermethylated tumors. Increased CTGF methylation was inversely correlated with the mesenchymal subtype mRNA gene signature (r = -0.21, p = 0.0026) and correlated with the atypical subtype (r = 0.32, p = 0.000002). Conclusions: Implementation of CTGF-M in routine diagnostic is feasible and correlates well with CTGF gene-expression levels and activation of tissue remodeling pathways. Therefore, CTGF-M might be instructive for stratifying HNSCC patients for CTGF targeting therapies. CTGF emerges as a promising prognostic marker independently of HPV status." @default.
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• W2947194687 date "2019-05-20" @default.
• W2947194687 modified "2023-09-25" @default.
• W2947194687 title "Connective tissue growth factor (CTGF) methylation status is associated with prognosis of patients with head and neck squamous cell carcinoma (HNSCC) treated with radiochemotherapy (RCHT): A multicenter study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)." @default.
• W2947194687 doi "https://doi.org/10.1200/jco.2019.37.15_suppl.6050" @default.
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