Recent progress in the study of methylated tumor suppressor genes in gastric cancer / 癌症

Gastric cancer is one of the most common malignancies and a leading cause of cancer mortality worldwide. The pathogenesis mechanisms of gastric cancer are still not fully clear. Inactivation of tumor suppressor genes and activation of oncogenes caused by genetic and epigenetic alterations are known to play significant roles in carcinogenesis. Accumulating evidence has shown that epigenetic silencing of the tumor suppressor genes, particularly caused by hypermethylation of CpG islands in promoters, is critical to carcinogenesis and metastasis. Here, we review the recent progress in the study of methylations of tumor suppressor genes involved in the pathogenesis of gastric cancer. We also briefly describe the mechanisms that induce tumor suppressor gene methylation and the status of translating these molecular mechanisms into clinical applications.

Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.</p><p><b>METHODS</b>All 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.</p><p><b>RESULTS</b>The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.</p><p><b>CONCLUSIONS</b>Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.</p>

ANGPTL4 gene silencing by short-hairpin RNA inhibits the migration of human colorectal cancer cell line HT29 / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of ANGPTL4 gene silencing on the migration of human colon cancer cells in vitro.</p><p><b>METHODS</b>The expression of ANGPTL4 in human colorectal cancer cell lines was detected by semi-quantitative RT-PCR. Following stable transfection with a short-hairpin RNA (shRNA) targeting ANGPTL4 gene in HT29 cells, ANGPTL4 mRNA and protein expressions were detected by semi-quantitative RT-PCR and direct ELISA, respectively, and the changes in cell migration ability and cell morphology were observed with transwell and immunofluorescence assays.</p><p><b>RESULTS</b>ANGPTL4 was expressed in most of the colorectal cancer cell lines. Compared with the control groups, HT29 cells with shRNA-mediated ANGPTL4 gene silencing showed significantly decreased expression of ANGPTL4 mRNA and protein (P<0.05) and lowered cell migration ability possibly due to decreased pseudopodia formation.</p><p><b>CONCLUSION</b>ANGPTL4 was expressed in most colorectal cancer cell lines. Decreased ANGPTL4 gene expression can inhibit the cell migration and pseudopodia formation in HT29 cells.</p>

Silencing of Adrm1 by RNA interference suppresses proliferation of colorectal cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects of the novel proteasome subunit Adrm1 knockdown by RNA interference on proliferation of colorectal cancer cells.</p><p><b>METHODS</b>The shRNA eukaryotic expression vector against Adrm1 was constructed and transfected into colon cancer RKO cells. The Adrm1-shRNA stable transfected clones were selected. Experimental cells were divided into 3 groups: the experimental group containing stable Adrm1-shRNA transfected cells, the control group containing only RKO colon cancer cells and stable empty vector transfected control group. The Adrm1 protein expression level was analyzed by Western blot. The colony-forming ability of the three groups was assessed by soft agar assay. The cell proliferation and apoptosis were analyzed by methyl thiazolyl tetrazolium (MTT) method and in situ end labeling (TUNEL) assay. Cell cycle changes were assayed by flow cytometry.</p><p><b>RESULTS</b>Adrm1-shRNA effectively suppressed Adrm1 expression in the experimental group. Silencing of Adrm1 in RKO cells significantly inhibited their anchorage-independent growth, only occasional individual colonies were formed. The apoptosis rate of experimental group was (12.4 +/- 1.1)%, significantly higher than that of the stable empty vector transfected control group. The proportion of G(0)/G(1) and S/G(2) phase cells in the experimental group was (41.2 +/- 1.1)% and (58.8 +/- 1.1)%, respectively. The cells were arrested at G(1) phase. In addition, Adrm1 RNA interference combined with 5-Fu treatment significantly suppressed colorectal cancer cell growth in vitro.</p><p><b>CONCLUSION</b>Silencing of Adrm1 by RNA interference can significantly suppress proliferation of RKO cells through inducing apoptosis and arresting the cell cycle. The combined application of Adrm1 RNA interference and chemotherapy may become as a novel therapeutic strategy for Adrm1 overexpressed colorectal cancer.</p>

High expression of proteasome subunit PSMA7 in colorectal cancer is significantly correlated with liver metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlation between the proteasome subunit PSMA7 expression in colorectal cancer and its role in liver metastasis.</p><p><b>METHODS</b>To identify the PSMA7 protein expression in 62 primary site colorectal cancers, 34 lymph node metastatic sites and 13 liver metastatic sites by immunohistochemistry and clarify the correlation of its expression with the clinicopathological parameters.</p><p><b>RESULTS</b>High expression of PSMA7 was detected in 38.7% (24/62) of primary site colorectal cancer, 52.9% (18/34) of lymph node metastatic sites and 100% (13/13) liver metastatic sites but not in the normal colorectal tissue. High expression of PSMA7 was significantly correlated with liver metastasis (P = 0.028). The survival rate was significantly lower in patients with high expression of PSMA7 than in those with low expression of PSMA7 (P = 0.0008). As well, in multivariate analysis, PSMA7 expression demonstrated to be an independent prognostic factor (P = 0.004, relative risk 5.057; 95% confidence interval, 1.682-15.201).</p><p><b>CONCLUSION</b>PSMA7 may play an important role in the colorectal cancer progression. Evaluation of PSMA7 expression in primary colorectal cancer at the time of surgery might be a valuable test in defining patients with a high risk of developing liver metastasis.</p>