miR-511-5p Suppresses Cell Migration, Invasion and Epithelial-Mesenchymal Transition Through Targeting PAK2 in Gastric Cancer.

As a malignant tumor, gastric cancer (GC) is closely related with gastric mucosa and has a high mortality in the world. Since microRNA (miRNA) has become more and more important in tumor research, we intend to find out the functional role and mechanism of miR-511-5p in GC. Firstly, miR-511-5p level was examined in human GC cell lines and tissues, and its effect on cell migration and invasion of BGC-823 or HGC-27 cells was tested by migration assay and transwell assay. Then, we confirmed the association between miR-511-5p and p21 activated kinase 2 (PAK2) by the luciferase reporter assay, and further assessed their role in cell migration and invasion. Moreover, we verified the function of miR-511-5p and PAK2 in epithelial-mesenchymal transition (EMT). In our study, miR-511-5p was downregulated in GC cell lines and tissues, and inversely associated with PAK2. Luciferase reporter assay confirmed that miR-511-5p could bind to PAK2. MiR-511-5p mimics significantly upregulated E-cadherin and downregulated N-cadherin, Vimentin and Snail, and consequently inhibited cell migration and invasion. However, reintroduction of PAK2 reversed the inhibitory function of miR-511-5p on BGC-823 and HGC-27 cells. Our research suggested that tumor-suppressive function of miR-511-5p in GC was inhibited by PAK2, and miR-511-5p/PAK2 axis may serve as a new strategy in GC management.

Clinical characteristics and predictors of permanent stoma in rectal cancer patients underwent anterior resections: the value of preoperative prognostic nutritional index.

OBJECTIVES: This study was aimed to investigate the correlation between preoperative prognostic nutritional index (PNI) and permanent stoma (PS) in patients with defunctioning stoma (DS) after anterior resections and, based on it, to reveal the clinical value of PNI on clinical strategies about the selection of stoma location. METHODS: A total of 281 consecutive rectal cancer patients who accepted anterior resection and DS in the National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University from June 2008 to June 2018 were enrolled in this study. Receiver operating characteristic (ROC) curve for PNI was performed to discriminate PS. Univariate and multivariate analysis were conducted to identify the clinical characteristics and risk factors for PS. Specific reasons for patients with DS turned into PS were reviewed. RESULTS: ROC curve analysis defined PNI cutoff level of 45.85 corresponding to PS (area under the curve (AUC) = 0.71, 77% sensitivity, 56.9% specificity). Low PNI (OR = 3.23, P = 0.005), tumor crossing the peritoneal reflection (PR) (OR = 3.42, P = 0.003), postoperative distant metastasis (OR = 6.31, P < 0.001) were independently associated with PS. Besides, anastomotic complications (31.4%), poor oncological outcomes (35.3%), and personal preferences (33.3%) were the specific reasons for patients turning into PS. CONCLUSIONS: Preoperative PNI is an independent prognostic factor to predict PS in patients who underwent anterior resection and DS. Therefore, combined with other clinical characteristics and predictors, preoperative measurements of PNI could provide a significant support for clinical decision on patients prepared to accept anterior resection and DS.

DNA methylation biomarkers in stool for early screening of colorectal cancer.

Objective: Detection of aberrant methylated genes in feces has been developed as an early screening method for colorectal cancer. The aim of this study was to probe the methylation status of SEPT9, BMP3, NDRG4, and SDC2 in stool and study whether methylation of these genes is associated with colorectal cancer. Materials and Methods: DNAs were isolated and purified from cancerous and non-cancerous stool samples and colorectal cancer tissue. Gene methylation levels were quantified by methylation-specific PCR on SEPT9, BMP3, NDRG4, and SDC2 and analyzed by a diagnostic model. Results: DNA methylation of SEPT9, NDRG4 and SDC2, but not BMP3, had diagnostic potential for detecting colorectal cancer. Moreover, integration of SEPT9, NDRG4, and SDC2 methylation demonstrated high feasibility for detecting colorectal cancer and adenoma, with better performance on colorectal cancer than adenoma. Conclusion: The methylation of SEPT9, NDRG4, and SDC2 in stool may be a potential biomarker for early screening of colorectal cancer.