Identification of lncRNAs Associated with Prognosis of Rectal Cancer by Comprehensive Bioinformatics Analysis Based on TCGA.

BACKGROUND: Although many advances have been made in the field of molecular biology, new approaches are still required to reveal the molecular mechanisms underlying the pathogenesis of rectal cancer and identify specific diagnostic and therapeutic targets. METHODS: Here, we determined the expression profiles of lncRNA, mRNA, and microRNA (miRNA) in rectal cancer, and constructed the lncRNA-mRNA-miRNA ceRNA networks to identify the hub lncRNAs, mRNAs, and miRNAs involved in this cancer. Moreover, survival analysis was performed to identify survival-related genes. RESULTS: A total of 69 DElncRNAs, 32 DEmiRNAs, and 84 DEmRNAs were included in the ceRNA network. Based on the ceRNA principle, lncRNA ADAMTS9-AS2 was predicted to regulate the expression of FOXF2 gene through competitive binding to miR-182. The result of log-rank test showed that three lncRNAs, five mRNAs, and one miRNA were associated with survival of rectal adenocarcinoma patients and multivariate Cox regression analysis identified four lncRNA signatures as prognostic factors. CONCLUSIONS: These findings add to our understanding on the molecular mechanisms underlying the pathogenesis of rectal cancer and reveal potential diagnostic and therapeutic targets.

Network analysis based on TCGA reveals hub genes in colon cancer.

Colorectal cancer (CRC) is the third most widespread cancer in the world. Although many advances have been made in molecular biology, novel approaches are still required to reveal molecular mechanisms for the diagnosis and therapy of colon cancer. In this study, we aimed to determine and analyse the hub genes of CRC. First, we explored the mRNA and microRNA (miRNA) expression profiles of colon carcinoma, then we screened target genes of differentially expressed miRNAs and obtained the intersection between differently expressed genes and target genes. Gene Ontology (GO) classification and KEGG pathway analysis of differently expressed genes were performed, and gene-miRNA and TF-gene-miRNA networks were constructed to identify hub genes, miRNAs, and TFs. In total, 3436 significant differentially expressed genes (1709 upregulated and 1727 downregulated) and 216 differentially expressed miRNAs (99 upregulated and 117 downregulated) were identified in colon cancer. These differentially expressed genes were significantly enriched in GO terms and KEGG pathways, such as cell proliferation, cell adhesion, and cytokine-cytokine receptor interaction signalling pathways. GCNT4, EDN2, and so on were located in the central hub of the co-expression network. MYC, WT1, mir-34a, and LEF1 were located in the central hub of the network of TF-gene-miRNA. These findings increase our understanding of the molecular mechanisms of colon cancer and will aid in identifying potential targets for diagnostic and therapeutic usage.

Diagnostic Value of Fecal MicroRNAs for Colorectal Cancer: a Meta-Analysis.

BACKGROUND: Though the fecal occult blood test is used for colorectal cancer (CRC) screening worldwide, it lacks sensitivity and specificity for screening an average-risk population. Many studies have suggested that fecal microRNAs (miRNAs) might serve as novel diagnostic indicators of colorectal cancer. However, inconsistent results have also been reported. This meta-analysis aimed to evaluate the feasibility of fecal miRNAs as biomarkers for colorectal neoplasia screening. METHODS: We systematically searched PubMed, Embase, and Google Scholar for publications concerning the diagnostic value of miRNAs isolated from stool for CRC screening. The quality of each study was scored using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Data from different studies were pooled to estimate the summary sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) using a bivariate model. Summary receiver operator characteristic curves (SROCs) were plotted, and areas under the SROC curve (AUC) were calculated to evaluate the overall test performance. Heterogeneity was tested with the I2 test, and publication bias was tested with Deeks' funnel plot asymmetry test. Potential sources of heterogeneity were analyzed through subgroup analyses and meta-regression. RESULTS: Eighteen studies from 9 articles, including 853 patients and 819 controls, were included in this meta-analysis. The pooled sensitivity, specificity, PLR, DLR, and DOR were 0.63 (95% confidence interval [CI]: 0.56 - 0.70), 0.86 (95% CI: 0.77 - 0.92), 4.47 (95% CI: 2.85 - 7.01), 0.43 (95% CI: 0.38 - 0.49), and 10.38 (95% CI: 6.85 - 15.73), respectively. The area under the SROC was 0.77. Meta-regression suggested that different countries (or regions) and sample sizes may be potential sources of heterogeneity. CONCLUSIONS: Fecal miRNAs are potentially useful noninvasive biomarkers for the diagnosis of CRC, and combining methylated gene markers or FOBT with miRNA markers may be an alternative approach.

Schistosoma japonicum infection modulates the development of allergen-induced airway inflammation in mice.

Asthma, a chronic inflammatory disorder of the airways, is coordinated by Th2 cells in both human asthmatics and animal models of allergic asthma. It has been shown that helminth infections including Schistosoma mansoni may modulate atopic diseases including asthma. In the present study, BALB/c mice were infected with bisexual and unisexual (male) S. japonicum, respectively, prior to ovalbumin (OVA) sensitization and challenge. Compared to mice with OVA sensitization/challenge alone, S. japonicum infection led to a significant decrease of eosinophil accumulation in bronchoalveolar lavage fluid (BALF) collected 48 h postchallenge, as well as to a marked reduction in inflammatory cell infiltration around the airways and pulmonary blood vessels. Compared to OVA-immunized uninfected mice, the level of OVA-specific serum IgE as well as interleukin (IL)-4 and IL-5 in BALF were reduced, but IL-10 was strongly elevated in mice with preexisting S. japonicum infection prior to OVA immunization. These results suggest that both bisexual and male S. japonicum infections may modulate the development of allergic asthma.

[Production and identification of chicken egg yolk antibodies against soluble egg antigen of Schistosoma japonicum].

OBJECTIVE: To produce and purify egg yolk immunoglobulin against soluble egg antigen (SEA) of Schistosoma japonicum, and evaluate its specificity and sensitivity. METHODS: 25-week old hen was intravenously and subcutaneously immunized with SEA of Schistosoma japonicum for 4 times. Each hen was first immunized with 60 microg SEA and subsequent injections were performed at 10-day intervals with 30 microg SEA. IgY was extracted from eggs of hen 35 d after the first inoculation by WD (water-dilution) method, eggs from non-immunized hen were used as negative control. The protein concentration of IgY was measured by BCA method, and IgY was analyzed by SDS-PAGE and Western blotting. SEA-based ELISA was used to evaluate the specificity and sensitivity of the IgY. RESULTS: 61 mg IgY was extracted from one egg. The results of SDS-PAGE and Western blotting demonstrated that the IgY contained one major protein band with molecular weight of 130,000 and could be recognized by SEA. Specific IgY could be immediately detected by SDS-PAGE and ELISA in the eggs laid by the hens from 10 days after the first immunization. On day 31 after the primary immunization, the antibody titer reached 1:1 600. 2.4 ng/ml SEA was detected by IgY based-sandwich ELISA, which indicated a high sensitivity of the purified IgY. CONCLUSION: Anti-SEA IgY with high specificity and sensitivity has been obtained and purified.

Schistosoma japonicum eggs modulate the activity of CD4+ CD25+ Tregs and prevent development of colitis in mice.

Crohn's disease (CD) is considered to be caused by a disorder of the immune system and helminth infections may interact with development of the disease. We induced colitis in mice by trinitrobenzenesulfonic acid (TNBS) and observed the effects of intraperitoneally injected eggs of Schistosoma japonicum on the course of the disease. The inflammation in the colon was reduced in egg-treated mice and secretion of IFN-gamma (a Th1 cytokine) by cultured spleen cells in vitro was greatly suppressed, and of IL-4, IL-5 and IL-10 (Th2 cytokines) significantly elevated after egg injection. Also, the percentage of regulatory T-cells (Tregs) was increased in the spleens of egg-exposed mice with TNBS-induced colitis compared to non-egg exposed animals. The data suggest that Tregs may be activated by S. japonicum eggs and play a role in restoring immune disorders in TNBS-induced colitis of mice.

[Suppression of Schistosoma japonicum eggs on TNBS-induced colitis in mice].

OBJECTIVE: To study the suppression of Schistosoma japonicum eggs against the trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. METHODS: 50 female BALB/c mice (6-8 week-old) were randomly divided into normal control group, ethanol control group, schistosome egg immunized control group, TNBS-induced colitis group and TNBS-induced colitis with egg immunization group. In TNBS-induced colitis with egg immunization group, mice were immunized 4 times with 10,000 schistosome eggs by intraperitoneal injection with one-week interval. On day 6 after the last immunization the mice were induced by TNBS and the body weight, histological change on colon and level of cytokines of mice were observed in egg-immunized and -unimmunized colitis mice. RESULTS: The unimmunized mice developed significant inflammation in colon with bloody mucus feces and decreased body weight after TNBS induction. Distinct hyperemia, edema and transmural inflammatory infiltration accompanied with ulceration were shown in colon. The level of IFN-gamma was (3.47 +/- 0.87) ng/ml and IL-4 was (146.06 +/- 45.76) pg/ml. However, in egg-immunized mice, the inflammation was suppressed greatly and the body weight recovered soon after TNBS induction. The production of IL-4 was enhanced to (598.50 +/- 135.90) pg/ml, and IFN-gamma was significantly diminished to (1.53 +/- 0.51) ng/ml. CONCLUSION: S.japonicum eggs protect mice from colitis induced by TNBS.