Search

Background and aims: Long interspersed element-1 (LINE-1) hypomethylation may play an important role in colorectal cancer (CRC). Studies were identified that investigated LINE-1 methylation levels in CRC compared with normal controls. Methods: The random-effects model was used to estimate standardized mean difference with 95% confidence intervals according to the heterogeneity between the studies. We explored the relationship between LINE-1 hypomethylation and microsatellite instability (MSI) status, clinical features, and molecular features in CRC patients using a fixed-effects model. Results: A total of 7396 CRC patients were included in the meta-analysis. LINE-1 methylation was significantly lower in CRC patients than in controls (P=0.000). Mean LINE-1 methylation was significantly lower in non-MSI-high than in MSI-high tumors (P=0.000). LINE-1 hypomethylation was found more frequently in patients with a family history compared with those without family history (P=0.002). Patients with left colon cancer had lower LINE-1 methylation than those with right colon cancer (P=0.001). LINE-1 methylation was not associated with body mass index or patient sex. LINE-1 hypomethylation was found in p21 lost tumors (P=0.000). LINE-1 methylation levels were not associated with KRAS or PIK3CA-mutation status. Conclusion: LINE-1 hypomethylation is a potential biomarker for risk of CRC and associated with various clinical and molecular features of CRC. [ABSTRACT FROM AUTHOR]

The trafficking protein particle complex 4 (TRAPPC4) is implicated in vesicle-mediated transport, but its association with disease has rarely been reported. We explored its potential interaction with ERK2, part of the ERK1/2 complex in the Extracellular Signal-regulated Kinase/ Mitogen-activated Protein Kinase (ERK-MAPK) pathway, by a yeast two-hybrid screen and confirmed by co-immunoprecipitation (Co-IP) and glutathione S-transferase (GST) pull-down. Further investigation found that when TRAPPC4 was depleted, activated ERK1/2 specifically decreased in the nucleus, which was accompanied with cell growth suppression and apoptosis in colorectal cancer (CRC) cells. Overexpression of TRAPPC4 promoted cell viability and caused activated ERK1/2 to increase overall, but especially in the nucleus. TRAPPC4 was expressed more highly in the nucleus of CRC cells than in normal colonic epithelium or adenoma which corresponded with nuclear staining of pERK1/2. We demonstrate here that TRAPPC4 may regulate cell proliferation and apoptosis in CRC by interaction with ERK2 and subsequently phosphorylating ERK1/2 as well as modulating the subcellular location of pERK1/2 to activate the relevant signaling pathway. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the effect of prophylactic regional liver chemotherapy during the perioperative period on improving survival and preventing liver metastases in patients with colorectal cancer (CRC). METHODS: A comprehensive retrieval of the relevant literature was performed by searching major biomedical database, mainly from Medline and Embase. Studies reported in the selected literature were categorized into two subgroups according to the type of therapy: a perioperative hepatic artery infusion subgroup and a perioperative portal vein infusion subgroup. Mortality and liver metastasis were analyzed using a fixed-effects model. Statistical analysis was performed using Review Manager software. RESULTS: The results of this meta-analysis illustrated that survival and the rate of liver metastasis in patients receiving perioperative hepatic artery infusion (HAI) chemotherapy were significantly better than for those receiving surgery alone (pooled relative risk 0.46 [95% CI: 0.31–0.69] and 0.44 [95% CI: 0.28–0.68], respectively, P= 0.0002), while survival and the rate of liver metastasis in patients receiving perioperative portal vein infusion (PVI) chemotherapy were not significantly different from those receiving surgery alone (pooled relative risk 0.98 [95% CI: 0.89–1.09], P= 0.73 and 0.86 [95% CI: 0.72–1.02], respectively. P= 0.08). CONCLUSION: As a method of regional liver chemotherapy, HAI might be able to improve survival and reduce the rate of liver metastasis in patients with advanced CRC. [ABSTRACT FROM AUTHOR]