The global histone modification pattern correlates with overall survival in metachronous liver metastasis of colorectal cancer
ABSTRACT Post-translational histone modifications are known to be altered in cancer tissues, and differences in the histone modification levels have recently been used to predict the clinical outcome in patients with certain types of cancer. In this study, we evaluated the immunohistochemical staining patterns of histone H3 dimethylation and acetylation in metachronous liver metastasis of colorectal carcinomas and examined its correlation with patient prognosis. Double 2 mm core tissue microarrays were made from 54 paraffin-embedded samples of liver metastasis from colorectal adenocarcinoma, and were examined by an immunohistochemical analysis of histone H3 lysine 4 (H3K4) dimethylation, histone, H3 lysine 9 (H3K9) dimethylation and histone H3 lysine 9 (H3K9) acetylation. Positive tumor cell staining for each histone modification was used to classify patients into low- and high-staining groups, which were then examined for correlations with the clinicopathological parameters and clinical outcome. Dimethylation of H3K4 correlated with the tumor histological type (P=0.043), and acetylation of H3K9 correlated with the tumor histological type (P=0.016). In addition, lower levels of H3K4 dimethylation correlated with a poor survival rate (P=0.035). The multivariate survival analysis showed that the H3K4 dimethylation status is an independent prognostic factor for colorectal cancer patients (P=0.011). We suggest that the pattern of histone modification as detected by immunohistochemistry may be an independent prognostic factor for metachronous liver metastasis of colorectal carcinomas.
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ABSTRACT: Histone post-translational modifications (PTMs) play an important role in the regulation of the expression of genes, including those involved in cancer development and progression. However, our knowledge of PTM patterns in human tumours is limited.Clinical Proteomics 01/2014; 11(1):24. DOI:10.1186/1559-0275-11-24
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ABSTRACT: Colorectal cancer (CRC) results from a stepwise accumulation of genetic and epigenetic alterations that transform the normal colonic epithelium into cancer. DNA methylation represents one of the most studied epigenetic marks in CRC, and three common epigenotypes have been identified characterized by high, intermediate and low methylation profiles, respectively. Combining DNA methylation data with gene mutations and cytogenetic alterations occurring in CRC is nowadays allowing the characterization of different CRC subtypes, but the crosstalk between DNA methylation and other epigenetic mechanisms, such as histone tail modifications and the deregulated expression of non-coding RNAs is not yet clearly defined. Epigenetic biomarkers are increasingly recognized as promising diagnostic and prognostic tools in CRC, and the potential of therapeutic applications aimed at targeting the epigenome is under investigation.Expert Review of Gastroenterology and Hepatology 05/2014; 8(8):1-14. DOI:10.1586/17474124.2014.924397 · 2.55 Impact Factor
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ABSTRACT: Colorectal cancer (CRC) causes approximately 600000 deaths annually and is the third leading cause of cancer mortality worldwide. Despite significant advancements in treatment options, CRC patient survival is still poor owing to a lack of effective tools for early diagnosis and a limited capacity for optimal therapeutic decision making. Since there exists a need to find new biomarkers to improve diagnosis of CRC, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to clinical practice. Epigenetic alterations are thought to hold great promise as tumor biomarkers. In this review, we will primarily focus on recent advances in the study of epigenetic biomarkers for colorectal cancer and discuss epigenetic biomarkers, including DNA methylation, microRNA expression and histone modification, in cancer tissue, stool, plasma, serum, cell lines and xenografts. These studies have improved the chances that epigenetic biomarkers will find a place in the clinical practices of screening, early diagnosis, prognosis, therapy choice and recurrence surveillance for CRC patients. However, these studies have typically been small in size, and evaluation at a larger scale of well-controlled randomized clinical trials is the next step that is necessary to increase the quality of epigenetic biomarkers and ensure their widespread clinical use.World Journal of Gastroenterology 04/2014; 20(15):4276-4287. DOI:10.3748/wjg.v20.i15.4276 · 2.43 Impact Factor