Discovery of Novel miRNAs in Colorectal Cancer: Potential Biological Roles and Clinical Utility.

Deregulated miRNAs are associated with colorectal cancer (CRC), with alterations depending on the tumor location. Novel tissue-specific miRNAs have been identified in different tumors and are associated with cancer. We used miRMaster to identify novel miRNAs in CRC from the TCGA and GEO data (discovery and validation groups). We used TCGA data from five tissues to analyze miRNA tissue specificity. miRDB was used to predict miRNA targets, and the UCSC Xena Browser was used to evaluate target expression. After successive analyses, we identified 15 novel miRNAs with the same expression patterns in CRC in both the discovery and validation groups. Four molecules (nov-miR-13844-5p, nov-miR-7154-5p, nov-miR-5035-3p, and nov-miR-590-5p) were differentially expressed in proximal and distal CRC. The nov-miR-3345-5p and nov-miR-13172-3p, which are upregulated in tumors, are only expressed in colorectal tissues. These molecules have been linked to a worse prognosis in right-sided colon and rectal carcinomas. An analysis revealed an association between eight novel miRNAs and 81 targets, mostly cancer-related genes, with varying expression based on tumor location. These findings provide new miRNAs with potential biological relevance, molecular biomarkers, and therapeutic targets for CRC treatment.

MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma.

Despite progress in treatment strategies, only ~24% of pancreatic ductal adenocarcinoma (PDAC) patients survive >1 year. Our goal was to elucidate deregulated pathways modulated by microRNAs (miRNAs) in PDAC and Vater ampulla (AMP) cancers. Global miRNA expression was identified in 19 PDAC, 6 AMP and 25 paired, histologically normal pancreatic tissues using the GeneChip 4.0 miRNA arrays. Computational approaches were used for miRNA target prediction/identification of miRNA-regulated pathways. Target gene expression was validated in 178 pancreatic cancer and 4 pancreatic normal tissues from The Cancer Genome Atlas (TCGA). 20 miRNAs were significantly deregulated (FC≥2 and p<0.05) (15 down- and 5 up-regulated) in PDAC. miR-216 family (miR-216a-3p, miR-216a-5p, miR-216b-3p and miR-216b-5p) was consistently down-regulated in PDAC. miRNA-modulated pathways are associated with innate and adaptive immune system responses in PDAC. AMP cancers showed 8 down- and 1 up-regulated miRNAs (FDR p<0.05). Most enriched pathways (p<0.01) were RAS and Nerve Growth Factor signaling. PDAC and AMP display different global miRNA expression profiles and miRNA regulated networks/tumorigenesis pathways. The immune response was enriched in PDAC, suggesting the existence of immune checkpoint pathways more relevant to PDAC than AMP.

Antibiotic prophylaxis for surgical site infection in people undergoing liver transplantation.

BACKGROUND: Surgical site infection is more frequent in liver transplantation than in other types of solid organ transplantation with different antibiotics. Studies have shown that the rate of surgical site infection varies from 8.8% to 37.5% after liver transplantation. Therefore, antimicrobial prophylaxis is likely an essential tool for reducing these infections. However, the literature lacks evidence indicating the best prophylactic antibiotic regimen that can be used for liver transplantation. OBJECTIVES: To assess the benefits and harms of antibiotic prophylactic regimens for surgical site infection in people undergoing liver transplantation. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and Latin American Caribbean Health Sciences Literature (LILACS). The most recent search was performed on 11 September 2015. SELECTION CRITERIA: All eligible randomised clinical trials comparing any antibiotic regimen versus placebo, versus no intervention or versus another antibiotic regimen for surgical site infection in liver transplant recipients, regardless of age, sex and reason for transplantation. Quasi-randomised studies and other observational studies were considered for data on harm if retrieved with search results for randomised clinical trials. DATA COLLECTION AND ANALYSIS: Two review authors selected relevant trials, assessed risk of bias of studies and extracted data. MAIN RESULTS: The electronic search identified 786 publications after removal of duplicates. From this search, only one seemingly randomised clinical trial, published in abstract form, fulfilled the inclusion criteria of this review. This trial was conducted at Shiraz Transplant Centre, Shiraz, Iran, where investigators randomly assigned a total of 180 consecutive liver transplant recipients. We judged the overall risk of bias of the trial published in abstract form as high. Researchers reported no numerical data but mentioned that 163 participants met the inclusion criteria after randomisation, and hence were included in the analyses. Most probably, the 17 excluded participants were high-risk liver transplant recipients. Trial authors concluded that they could find no differences between the two antibiotic regimens - ceftriaxone plus metronidazole versus ampicillin-sulbactam plus ceftizoxime - when given to liver transplant recipients. Review authors could not reconfirm the analyses because, as it has been mentioned, trial authors provided no trial data for analyses. AUTHORS' CONCLUSIONS: Benefits and harms of antibiotic prophylactic regimens for surgical site infection in liver transplantation remain unclear. Additional well-conducted randomised clinical trials adhering to SPIRIT (Spirit Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) guidelines are needed to determine the exact role of antibiotic prophylactic regimens in patients undergoing liver transplantation.