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Phosphohistone H3 (pHH3) is a prognostic and epithelial to mesenchymal transition marker in diffuse gliomas.

ABSTRACT: The World Health Organization (WHO) grading of gliomas stratifies tumors by histology. However, the aggressiveness of tumors in each grade still shows great heterogeneity. Phosphohistone H3 (pHH3) has been reported as an accurate marker of cells within the mitotic phase of the cell cycle in many kinds of cancers. To evaluate the role of pHH3 in predicting patient outcome and to annotate the functions of pHH3 in WHO grade II-IV gliomas, we analyzed the expression pattern of pHH3 and pHH3 associated genes by IHC and mRNA expression profiling. Phosphohistone H3, mRNA enrichment of histone H3 and associated gene signature all showed prognostic value in adult diffuse gliomas. Gene set enrichment analysis suggested that the expression of pHH3 had positive correlation with both epithelial to mesenchymal transition and immune response. These findings suggest that subgroups of diffuse gliomas defined by pHH3 and pHH3 signatures possess distinctive prognostic and biological characteristics.

SUBMITTER: Zhu P

PROVIDER: S-EPMC5216701 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Phosphohistone H3 (pHH3) is a prognostic and epithelial to mesenchymal transition marker in diffuse gliomas.

Zhu Ping P Zhang Chuan-Bao CB Yang Pei P Chen Jing J Liu Yu-Qing YQ Hu Hui-Min HM Huang Hua H Bao Zhao-Shi ZS Zhang Wei W Kong Wei-Jia WJ Jiang Tao T

Oncotarget 20160701 29

The World Health Organization (WHO) grading of gliomas stratifies tumors by histology. However, the aggressiveness of tumors in each grade still shows great heterogeneity. Phosphohistone H3 (pHH3) has been reported as an accurate marker of cells within the mitotic phase of the cell cycle in many kinds of cancers. To evaluate the role of pHH3 in predicting patient outcome and to annotate the functions of pHH3 in WHO grade II-IV gliomas, we analyzed the expression pattern of pHH3 and pHH3 associat ...[more]

PMID: 27323851

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Project description:BACKGROUND:Periampullary cancers (PAC) including pancreatic, ampulla of Vater (AOV), and common bile duct (CBD) cancers are highly aggressive with a lack of useful prognostic markers beyond T stage. However, T staging can be biased due to the anatomic complexity of this region. Recently, several markers related to cancer stem cells and epithelial-mesenchymal transition (EMT) such as octamer transcription factor-4 (Oct4) and fibroblast growth factor receptor 1 (FGFR1) respectively, have been proposed as new promising markers in other solid cancers. The aim of this study was to assess the expression and prognostic significance of stem cell/EMT markers in PACs. METHODS:Formalin-fixed, paraffin-embedded tissues of surgically excised PACs from the laboratory archives from 1998 to 2014 were evaluated by immunohistochemical staining for stem cell/EMT markers using tissue microarray. The clinicopathologic parameters were documented and statistically analyzed with the immunohistochemical findings. Survival and recurrence data were collected and analyzed. RESULTS:A total of 126 PAC cases were evaluated. The average age was 63?years, with 76 male and 50 female patient samples. Age less than 74?years, AOV cancers, lower T & N stage, lower tumor size, no lymphatic, vascular, perineural invasion and histologic well differentiation, intestinal type, no fibrosis, severe inflammation were significantly associated with the better overall survival High expression levels of FGFR1 as well as CK20, CDX2, and VEGF were significantly related to better overall survival, while other stem cell markers were not related. Similar findings were observed for tumor recurrence using disease-free survival. CONCLUSIONS:In addition to other clinicopathologic parameters, severe fibrosis was related to frequent tumor recurrence, and high FGFR1 expression was associated with better overall survival. Histologic changes such as extensive fibrosis need to be investigated further in relation to EMT of PACs.

Project description:BackgroundGliomas are the most common primary malignant tumours of the central nervous system (CNS). To improve the prognosis of glioma, it is necessary to identify molecular markers that may be useful for glioma therapy. HOXC6, an important transcription factor, is involved in multiple cancers. However, the role of HOXC6 in gliomas is not clear.MethodsBioinformatic and IHC analyses of collected samples (n = 299) were performed to detect HOXC6 expression and the correlation between HOXC6 expression and clinicopathological features of gliomas. We collected clinical information from 177 to 299 patient samples and estimated the prognostic value of HOXC6. Moreover, cell proliferation assays were performed. We performed Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) based on ChIP-seq and public datasets to explore the biological characteristics of HOXC6 in gliomas. RNA-seq was conducted to verify the relationship between HOXC6 expression levels and epithelial-mesenchymal transition (EMT) biomarkers. Furthermore, the tumour purity, stromal and immune scores were evaluated. The relationship between HOXC6 expression and infiltrating immune cell populations and immune checkpoint proteins was also researched.ResultsHOXC6 was overexpressed and related to the clinicopathological features of gliomas. In addition, knockdown of HOXC6 inhibited the proliferation of glioma cells. Furthermore, increased HOXC6 expression was associated with clinical progression. The biological role of HOXC6 in gliomas was primarily associated with EMT and the immune microenvironment in gliomas. High HOXC6 expression was related to high infiltration by immune cells, a low tumour purity score, a high stromal score, a high immune score and the expression of a variety of immune checkpoint genes, including PD-L1, B7-H3 and CLTA-4.ConclusionsThese results indicated that HOXC6 might be a key factor in promoting tumorigenesis and glioma progression by regulating the EMT signalling pathway and might represent a novel immune therapeutic target in gliomas.

Dataset Information

Phosphohistone H3 (pHH3) is a prognostic and epithelial to mesenchymal transition marker in diffuse gliomas.

Publications

Phosphohistone H3 (pHH3) is a prognostic and epithelial to mesenchymal transition marker in diffuse gliomas.

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