ZMYND8 expression combined with pN and pM classification as a novel prognostic prediction model for colorectal cancer: Based on TCGA and GEO database analysis
CANCER BIOMARKERS
Authors: Chen, Jiewei; He, Qingmei; Wu, Peishan; Fu, Jianchang; Xiao, Yongbo; Chen, Keming; Xie, Dan; Zhang, Xinke
Abstract
BACKGROUND: Zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8 (ZMYND8) is closely correlated with tumor proliferation and invasiveness. However, its prognostic value has not been estimated in colorectal cancer (CRC). OBJECTIVE: We aimed to elucidate the prognostic significance of ZMYND8 expression and the pN and pM classification supplemented by its expression in CRCs. METHODS: The candidate gene ZMYND8 is identified by TCGA database and GEO database, and then we retrospectively evaluated the status and prognostic significance of ZMYND8 expression of 174 patients with CRC. RESULTS: Online data showed high expression of ZMYND8 is closely correlated with worse overall survival. Our study revealed high expression of ZMYND8 in CRC patients was significantly associated with worse overall and disease-free survival (P < 0.05), and was an independently adverse prognostic factor for overall survival (P < 0.001) and disease-free survival (P = 0.001) by univariate and multivariate analysis. C-index to combined prognostic model containing the pN, pM classification supplemented by the status of ZMYND8 expression showed improved predictive ability comparing with the pN and pM classification model (C-index of 0.597 vs. 0.545, respectively). CONCLUSION: The combined prognostic model could improve the ability to determine the clinical outcome of patients with CRC.
Z4 Complex Member Fusions in NUT Carcinoma: Implications for a Novel Oncogenic Mechanism
MOLECULAR CANCER RESEARCH
Authors: Shiota, Hitoshi; Elya, Janine E.; Alekseyenko, Artyom A.; Chou, Pauline M.; Gorman, Shelby A.; Barbash, Olena; Becht, Kelly; Danga, Kristina; Kuroda, Mitzi I.; Nardi, Valentina; French, Christopher A.
Abstract
Nuclear protein in testis (NUT) carcinoma (NC) is a rare, distinctly aggressive subtype of squamous carcinoma defined by the presence of NUT-fusion oncogenes resulting from chromosomal translocation. In most cases, the NUT gene (NUTM1) is fused to bromodomain containing 4 (BRD4) forming the BRD4-NUT oncogene. Here, a novel fusion partner to NUT was discovered using next-generation sequencing and FISH from a young patient with an undifferentiated malignant round cell tumor. Interestingly, the NUT fusion identified involved ZNF592, a zinc finger containing protein, which was previously identified as a component of the BRD4-NUT complex. In BRD4-NUT-expressing NC cells, wild-type ZNF592 and other associated "Z4" complex proteins, including ZNF532 and ZMYND8, colocalize with BRD4-NUT in characteristic nuclear foci. Furthermore, ectopic expression of BRD4-NUT in a non-NC cell line induces sequestration of Z4 factors to BRD4-NUT foci. Finally, the data demonstrate the specific dependency of NC cells on Z4 modules, ZNF532 and ZNF592. Implications: This study establishes the oncogenic role of Z4 factors in NC, offering potential new targeted therapeutic strategies in this incurable cancer. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/12/1826/F1.large.jpg. (C) 2018 AACR.