WTAP is overexpressed in cholangiocarcinoma and regulates motility of cholangiocarcinoma cells.
The role of Snail and serpin peptidase inhibitor clade A member 1 (serpinA1) in tumorigenesis has been previously identified. However, the exact role and mechanism of these proteins in progression of colorectal cancer (CRC) are controversial. In this study, we investigated the role of Snail and serpinA1 in colorectal cancer (CRC) and examined the mechanisms through which these proteins mediate CRC progression. Immunohistochemical analysis of 528 samples from patients with CRC showed that elevated expression of Snail or serpinA1 was correlated with advanced stage, lymph node metastasis, and poor prognosis. Moreover, we detected a correlation between Snail and serpinA1 expression. Functional studies performed using the CRC cell lines DLD-1 and SW-480 showed that overexpression of Snail or serpinA1 significantly increased CRC cell invasion and migration. Conversely, knockdown of Snail or serpinA1 expression suppressed CRC cell invasion and migration. ChIP analysis revealed that Snail regulated serpinA1 by binding to its promoter. In addition, fibronectin mediated Snail and serpinA1 signaling was involved in CRC cell invasion and migration. Taken together, our data showed that Snail and serpinA1 promoted CRC progression through fibronectin. These findings suggested that Snail and serpinA1 were novel prognostic biomarkers and candidate therapeutic targets in CRC.
Surgical resection revealed superior outcomes in the treatment of resectable CRLMs, particularly in cases with a hepatic tumor size > 3 cm.
BackgroundDespite the clinical significance of liver metastases, the difference between molecular and cellular changes in primary colorectal cancers (CRC) and matched liver metastases is poorly understood.MethodsIn order to compare gene expression patterns and identify fusion genes in these two types of tumors, we performed high-throughput transcriptome sequencing of five sets of quadruple-matched tissues (primary CRC, liver metastases, normal colon, and liver).ResultsThe gene expression patterns in normal colon and liver were successfully distinguished from those in CRCs; however, RNA sequencing revealed that the gene expression between primary CRCs and their matched liver metastases is highly similar. We identified 1895 genes that were differentially expressed in the primary carcinoma and liver metastases, than that in the normal colon tissues. A major proportion of the transcripts, identified by gene expression profiling as significantly enriched in the primary carcinoma and metastases, belonged to gene ontology categories involved in the cell cycle, mitosis, and cell division. Furthermore, we identified gene fusion events in primary carcinoma and metastases, and the fusion transcripts were experimentally confirmed. Among these, a chimeric transcript resulting from the fusion of RNF43 and SUPT4H1 was found to occur frequently in primary colorectal carcinoma. In addition, knockdown of the expression of this RNF43-SUPT4H1 chimeric transcript was found to have a growth-inhibitory effect in colorectal cancer cells.ConclusionsThe present study reports a high concordance of gene expression in the primary carcinoma and liver metastases, and reveals potential new targets, such as fusion genes, against primary and metastatic colorectal carcinoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2596-3) contains supplementary material, which is available to authorized users.
Despite wide acceptance of the chronic gastritis-intestinal metaplasia-dysplasia-carcinoma sequence, especially for intestinal-type gastric adenocarcinoma, the precise nature of the subtle precursor lesions of gastric cancer remains to be delineated. For example, pit dysplasia with surface foveolar maturation is not well defined, nor is its prevalence and biological characteristics well characterized. We have evaluated the surrounding gastric mucosa of 414 gastric cancers for the presence of gastric pit dysplasia. We investigated its relationship with various clinicopathological and immunophenotypic features of gastric adenocarcinoma, as well as the severity and extent of any surrounding gastritis and intestinal metaplasia. p53 expression and Ki-67 proliferation index were also evaluated. We have found that 21.0% (n=87) of gastric cancer cases showed pit dysplasia in adjacent gastric mucosa. Gastric cancers with pit dysplasia were significantly associated with older age, male sex, body/fundic location, and intestinal histologic type (P<0.05). Interestingly, gastric mucin-containing intestinal metaplasia (incomplete intestinal metaplasia) was highly associated with adenocarcinoma with pit dysplasia (P=0.000). In addition, MUC6 expression in gastric adenocarcinoma was associated with pit dysplasia (P=0.036). p53 overexpression and increased Ki-67 proliferation index were more evident in gastric pit dysplasia compared with adjacent gastric mucosa. We suggest that gastric pit dysplasia is an important candidate precursor of gastric adenocarcinoma and may represent another morphologic step in the pathogenesis of gastric adenocarcinoma, especially of intestinal type. More detailed prospective studies are needed to determine the precise significance of these findings.
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