Bioinformatics and survival analysis of glia maturation factor-γ in pan-cancers.

BACKGROUND: Glia maturation factor-γ (GMFG) is reported to inhibit the actin nucleation through binding to the actin-related protein-2/3 complex (Arp2/3). Considering the main function of GMFG in actin remodeling, which is vital for immune response, angiogenesis, cell division and motility, GMFG is supposed to have important roles in tumor development, while up to now, only two studies described the role of GMFG in cancers. By investigating the clinical values of GMFG using The Cancer Genome Atlas (TCGA) data and the functional mechanisms of GMFG through analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments, this study was aimed to better understand the impact of GMFG in pan-cancers and to draw more attentions for the future research of GMFG. METHODS: RNA-seq and clinical data of cancer patients were collected from TCGA and analyzed by the Kaplan-Meier methods. GO and KEGG analyses were conducted using the online tools from the Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: Compared to the corresponding normal samples, GMFG was significantly upregulated in glioblastoma (GBM), kidney clear cell carcinoma (KIRC), lower grade glioma (LGG), acute myeloid leukemia (LAML), and pancreatic cancer (PAAD), testicular cancer (TGCT), but was downregulated in kidney chromophobe (KICH), lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) (P < 0.05 for all). High expression of GMFG predicted worse OS in GBM (HR = 1.5, P = 0.017), LGG (HR = 2.2, P < 0.001), LUSC (HR = 1.4, P = 0.022) and ocular melanomas (UVM) (HR = 7, P < 0.001), as well as worse DFS in LGG (HR = 1.8, P < 0.001) and prostate cancer (PRAD) (HR = 1.9, P = 0.004). In contrast, high expression of GMFG was associated with better OS in skin cutaneous melanoma (SKCM) (HR = 0.59, P < 0.001) and thymoma (THYM) (HR = 0.098, P = 0.031), as well as better DFS in bile duct cancer (CHOL) (HR = 0.2, P = 0.003). GMFG was mainly involved in the immune response, protein binding and cytokine-cytokine receptor interaction pathways, and was positively associated with multiple immunomodulators in most cancers. CONCLUSION: Our study preliminarily identified that GMFG may cause different survivals for different cancers through modulating tumor progression, immune response status and tissue-specific tumor microenvironment (TME).

Breastfeeding from mothers carrying HBV would not increase the risk of HBV infection in infants after proper immunoprophylaxis.

INTRODUCTION: Previously meta-analysis had different conclusions about the role of breastfeeding in mother-to-child transmission (MTCT) of hepatitis B virus (HBV). We aimed to carry out an updated meta-analysis based on current published evidence to explore that whether breastfeeding increase the risk of HBV infection from mothers carrying HBV after proper immunoprophylaxis in the infants or not. EVIDENCE ACQUISITION: Databases searched from January 1st,2000 to August 1st,2016 included PubMed searching engine, Cochrane Library, Embase database, Chinese National Knowledge Infrastructure, VIP Chinese database, and Wanfang Chinese database. EVIDENCE SYNTHESIS: 17 studies were incorporated into our meta-analysis. Our result showed that there was no significant difference between the breastfeeding group and the non-breastfeeding group (ORs=1.01, 95%CI: 0.75-1.36, I2=0). Further, there was no significant difference between the cases and controls in HBVac group (ORs=1.08, 95%CI: 0.42-2.76, I2=0) and in HBIG combined with HBVac group (ORs=0.97, 95%CI: 0.68-1.37, I2=0). CONCLUSIONS: Our update meta-analysis indicated that breastfeeding would not increase the risk of HBV injection from mothers carrying HBV after proper immunoprophylaxis in the infants. The results suggest that mother carrying HBV can breastfeed their babies after proper immunoprophylaxis in the infants.

Clinicopathological parameters and survival of invasive epithelial ovarian cancer by histotype and disease stage.

Aim: To investigate clinicopathological parameters and histotype-specific survival of epithelial ovarian cancer by stage using the 2014 WHO classification. Patients & methods: Patients were obtained from the SEER database. Multivariate and univariate Cox regression analyses were applied to assess survival outcomes. Results: Irrespective of stages, low-grade serous and endometrioid had the best survival rates. In localized and regional stages, the poorest survival rates were detected for carcinosarcoma and malignant Brenner tumors, but in distant stage, the worst prognoses were observed in mucinous, clear cell and carcinosarcoma (p < 0.05 for all). Conclusion: Our study displayed significant differences in clinicopathological parameters and histotype-specific survival by stages that reflected current consensus on histotype classification and pathogenesis of epithelial ovarian cancer.

Comprehensive investigation of aberrant microRNA profiling in bladder cancer tissues.

There has been accumulative evidence that microRNAs (miRNAs) play essential roles in the tumorigenesis and progression of bladder cancer. However, individual studies and small sample size caused discrepant outcomes. Thus, the current study focused on a comprehensive profiling of all differentially expressed miRNAs in a total of 519 bladder cancer tissue samples, based on miRNA microarray data. Altogether, 11 prioritized miRNAs stated by 21 published microarray datasets, including five down-regulated (miR-133a-3p, miR-1-3p, miR-99a-5p, miR-490-5p, and miR-133b) and six up-regulated candidate miRNAs (miR-182-5p, miR-935, miR-518e-3p, miR-573, miR-100-3p, and miR-3171) were analyzed with vote-counting strategy and a Robust Rank Aggregation method. Subsequently, miRNA in silico target prediction and potential pathway enrichment analysis were performed to investigate the prospective molecular mechanism of miRNAs in the tumorigenesis of bladder cancer. We found that most of the relative pathways of the aberrantly expressed miRNAs found in the current study were closely correlated with different biological processes, cellular components, molecular functions, cancer pathogeneses, and some cell signalings, such as Wnt signaling, insulin/IGF, PI3 kinase, and FGF signaling pathways. Hence, a comprehensive overview on the miRNA expression pattern in bladder cancer tissues was gained by the current study. These miRNAs might be involved in the tumorigenesis and deterioration of bladder cancer.

Impact of CAG repeat length in the androgen receptor gene on male infertility - a meta-analysis.

CAG repeats are polymorphic nucleotide repeats present in the androgen receptor gene. Many studies have estimated the association between CAG repeat length and male infertility, but the conclusions are controversial. Previous meta-analyses have come to different conclusions; however, new studies have been published. An updated meta-analysis was conducted. PubMed, CBM, CNKI and Web of Science databases were systematically searched for studies published from 1 January 2000 to 1 October 2015. Case-control studies on the association between CAG repeat length and male infertility using appropriate methodology were included. Forty studies were selected, including 3858 cases and 3161 controls. Results showed statistically significantly longer CAG repeat length among cases compared with controls (SMD = 0.14; 95% CI, 0.02-0.26). Shorter repeat length was associated with a lower risk of male infertility compared with a longer repeat length in the overall analysis (OR = 0.79, 95% CI: 0.66-0.95). Moreover, CAG repeat length was associated with male infertility in Caucasian populations, but not Asian or Egyptian populations. Subgroup analysis revealed no significant difference in German populations, but CAG repeat length was associated with male infertility in China and the USA. There were no significant differences between cases and controls in azoospermia and severe oligozoospermia.

Asperolide A induces apoptosis and cell cycle arrest of human hepatoma cells with p53-Y220C mutant through p38 mediating phosphorylation of p53 (S33).

Asperolides A (AA), one of the new tetranorlabdane diterpenoids, is proved to inhibit the proliferation of lung cancer cells and bone metastasis of breast cancer cells. Herein, we report that AA induces apoptosis and cell cycle arrest of hepatoma cells. It intensely inhibits proliferation of Huh-7 cell, compared with HepG-2 and L02 cells. AA elevates the activity of mitogen-activated protein kinases (MAPKs), in which the activation of ERK and JNK improves cell survival. However, phosphorylation of p53 at S33 by p38 activation could be a principal factor in the AA-induced apoptosis and G2/M cell cycle arrest of Huh-7 cells. The S33 site of p53-Y220C mutant, as the specific activation site of p38, reactivates the wild-type function of mutant p53 protein, which leads to a higher sensitivity of Huh-7 cells to AA. These results provide new insights into the molecular mechanisms of AA as a developing mutant p53 rescue drug.

Clinical significances of p27 in digestive tract cancers: a comprehensive analysis on immunohistochemistry staining, published literatures, microarray and RNA-seq data.

In the present study, we conducted a comprehensive analysis on the clinical roles of p27 protein and p27 gene in digestive tract cancers (DTCs). First, we performed immunohistochemistry staining and found that p27 protein was down-regulated in DTCs. Then we collected 62 publications and calculated the combined hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (95% CIs) to clarify the relationships of p27 protein expression with prognoses and clinicopathological parameters. The overall HRs indicated that the down-regulated p27 protein was an independent prognostic biomarker for overall survival (HR: 1.58, 95% CI: 1.38-1.81, P < 0.0001) but not for disease-free survival and cancer-specific survival. The combined ORs indicated that a low expression of p27 protein was positively related to lymph node metastasis (OR: 2.15, 95% CI: 1.57-2.96, P < 0.0001), distant metastasis (OR: 2.02, 95% CI: 1.12-3.63, P = 0.019) and pathology grading (OR: 2.14, 95% CI: 1.75-2.62, P < 0.0001). Additionally, 60 DTCs-related microarray and RNA-seq datasets were obtained to investigate the expression level and clinical value of p27 gene in DTCs patients. We found that the expression level of p27 gene in DTCs was similar to that in normal controls. And no significant associations of p27 gene expression with prognoses and clinicopathological factors were observed. In conclusion, according to our results, it was p27 protein, but not p27 gene, that can function as an effective biomarker to predict the clinical outcome in patients with DTCs. The down-regulation of p27 protein in DTCs may not result from the altered expression of p27 gene.

MicroRNA-671-3p inhibits the development of breast cancer: A study based on in vitro experiments, in-house quantitative polymerase chain reaction and bioinformatics analysis.

MicroRNAs (miRNAs or miRs) are highly conserved small noncoding RNA molecules involved in gene regulation. An increasing number of studies have demonstrated that miRNAs act as oncogenes or antioncogenes in various types of cancer, including breast cancer (BC). However, the exact role of miR­671­3p in BC has not yet been reported. In the present study, in vitro experiments were implemented to explore the effects of miR­671­3p on the proliferation and apoptosis of BC cells, and reverse transcription­quantitative polymerase chain reaction was conducted using in­house clinical BC samples to address the expression level and clinical value of miR­671­3p in BC. Simultaneously, miR­671­3p target genes were collected, and subsequent bioinformatics analyses were executed to probe the potential signaling pathway through which miR­671­3p influenced the occurrence and progression of BC. According to the results, the expression level of miR­671­3p was lower in BC tissues compared with that in adjacent non­tumorous tissues (P=0.048), and the area under the curve was 0.697 (95% confidence interval=0.538­0.856), with a sensitivity and specificity of 0.818 and 0.579, respectively. Forced miR­671­3p expression in the BC cell line MDA­MB­231 evidently arrested cell proliferation and induced cell apoptosis. Furthermore, in silico enrichment analyses suggested that miR­671­3p may be involved in the initiation and progression of BC through the targeting of genes associated with the Wnt signaling pathway. In conclusion, the present study findings suggested that miR­671­3p may function as a tumor suppressor in BC by influencing the Wnt signaling cascade, which provides a prospective molecular target for the therapy of BC.

Efficacy of fibrin glue versus sutures for attaching conjunctival autografts in pterygium surgery: a systematic review with meta-analysis and trial sequential analysis of evidence.

Previous meta-analyses have been conducted to compare the efficacy of fibrin glue (FG) versus sutures in pterygium surgery; however, additional clinical trials have since been published. Therefore, we conducted an updated meta-analysis to further explore the association between FG application in pterygium surgery, and the recurrence rate, complication rate, and surgical duration. An electronic literature search for eligible studies published before July 29, 2016 was conducted across multiple databases. Odds ratios (ORs), standardized mean difference (SMD), and 95% confidence intervals (CI) were calculated. Publication bias of the included articles was evaluated by funnel plots. Differences in recurrence rate and complication rate between the FG and suture groups were evaluated in terms of OR with 95% CI, and SMD with 95% CI were used to estimate the difference in surgical duration. Trial sequential analysis (TSA) was used to determine whether the currently available evidence was sufficient and conclusive. Twenty-four studies were included in this study. The pooled ORs for recurrence rate and complication rate were 0.35 and 1.121, respectively. The pooled SMD for surgical duration was -4.142. The TSA results indicated that evidence of the effect was sufficient in the recurrence group and surgical duration group. Although there was no difference in complication rate between FG and sutures, the apparent advantages of FG over sutures are shorter surgical duration and greater reduction in the recurrence rate of pterygium.

Shorter GGN Repeats in Androgen Receptor Gene Would Not Increase the Risk of Prostate Cancer.

The association between the polymorphic GGN repeat in androgen receptor gene and prostate cancer susceptibility has been studied extensively. But the results of these polymorphisms with prostate cancer risk remain inconclusive. Previous meta-analysis showed short GGN repeats (≤16 repeats) had high risks for prostate cancer compared with longer GGN repeats (>16 repeats). Many studies have been published since the release of the previous meta-analysis. Here, we conducted an updated meta-analysis to demonstrate whether short repeats have higher risks for prostate cancer compared to long repeats. Five databases (PubMed, EMBASE, Cochrane Library, The China National Knowledge Infrastructure, and Web of Science) were last searched until January 1, 2016. Random- or fixed-effects model was performed based on the heterogeneity among studies. The potential publication bias was assessed via Begg funnel plot and Egger regression test. Twelve out of 157 studies were extracted. The result indicated that there was no significant difference between short repeat group and long repeat group in the overall analysis ( I2 = 80.6%, P = .000, odds ratio = 1.31, 95% confidence interval: 0.93-1.83). There was no association between the length of GGN repeats and the occurrence of prostate cancer in both Caucasian and African American ( I2 = 6.7%, P = .359, odds ratio = 1.11, 95% confidence interval: 0.94-1.32; and I2 = 74.1%, P = .050, odds ratio = 0.963, 95% confidence interval: 0.36-2.58). Our result demonstrated that a shorter GGN repeat polymorphism cannot increase the risk of prostate cancer compared to the longer GGN repeats. That's different with previous meta-analysis.

The impact of atosiban on pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer: A meta-analysis.

BACKGROUND: Atosiban is administered to women undergoing in vitro fertilization-embryo transfer (IVF-ET) to improve pregnancy outcomes. However, the results of this treatment were controversial. We conducted this meta-analysis to investigate whether atosiban improves pregnancy outcomes in the women undergoing in vitro fertilization (IVF). METHODS: Databases of PubMed, EMBASE, Web of Science, China BioMedicine, and Google Scholar were systematically searched. Meta-analyses were performed to investigate whether atosiban improves pregnancy outcomes in the women undergoing IVF. RESULTS: Our results showed that atosiban was associated with higher implantation (OR = 1.63, 95% CI: 1.17-2.27; P = 0.004) and clinical pregnancy (OR = 1.84, 95% CI: 1.31-2.57; P < 0.001) rates. However, atosiban showed no significant association with the miscarriage, live birth, multiple pregnancy or ectopic pregnancy rates. When a further subgroup analysis was performed in the women undergoing repeated implantation failure (RIF), implantation (OR = 1.93, 95% CI: 1.45-2.57; P < 0.001), clinical pregnancy (OR = 2.48, 95% CI: 1.70-3.64; P <0.001) and the live birth (OR = 2.89, 95% CI: 1.78-4.67; P < 0.001) rates were significantly higher in the case group. Nevertheless, no significant difference was detected in the miscarriage and multiple pregnancy rates between the case and control groups. CONCLUSION: Atosiban may be more appropriate for women undergoing RIF and play only a limited role in improving pregnancy outcomes in the general population of women undergoing IVF. These conclusions should be verified in large and well-designed studies.

Association between the ERCC2 Asp312Asn polymorphism and risk of cancer.

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. The relationship between genetic polymorphisms and the risk of cancers has been widely researched. Excision repair cross-complementing group 2 (ERCC2) gene plays important roles in the nucleotide excision repair pathway. There is contrasting evidence on the association between the ERCC2 Asp312Asn polymorphism and the risk of cancer. We conducted a comprehensive meta-analysis in order to assess the correlation between these factors. We searched the PubMed, EMBASE, Science Direct, Web of Science, and CNKI databases for studies published from January 1, 2005 to January 1, 2016. Finally, 86 articles with 38,848 cases and 48,928 controls were included in the analysis. The overall analysis suggested a significant association between the ERCC2 Asp312Asn polymorphism and cancer risk. Furthermore, control source, ethnicity, genotyping method, and cancer type were used for subgroup analysis. The result of a trial sequential analysis indicated that the cumulative evidence is adequate; hence, further trials were unnecessary in the overall analysis for homozygote comparison. In summary, our results suggested that ERCC2 Asp312Asn polymorphism is associated with increased cancer risk. A significantly increased cancer risk was observed in Asian populations, but not in Caucasian populations. Furthermore, the ERCC2 Asp312Asn polymorphism is associated with bladder, esophageal, and gastric cancers, but not with breast, head and neck, lung, prostate, and skin cancers, and non-Hodgkin lymphoma. Further multi-center, well-designed studies are required to validate our results.

Impact of partial DAZ1/2 deletion and partial DAZ3/4 deletion on male infertility.

This study aims to investigate the effect of the partial DAZ1/2 deletion and partial DAZ3/4 deletion on male infertility through a comprehensive literature search. All case-control studies related to partial DAZ1/2 and DAZ3/4 deletions and male infertility risk were included in our study. Odd ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association and its precision, respectively. Eleven partial DAZ1/2 deletion and nine partial DAZ3/4 deletion studies were included. Partial DAZ1/2 deletion was significantly associated with male infertility risk in the overall analysis (ORs=2.58, 95%CI: 1.60-4.18, I(2)=62.1%). Moreover, in the subgroup analysis stratified by ethnicity, partial DAZ1/2 deletion was significantly associated with male infertility risk in the East Asian populations under the random effect model (ORs=2.96, 95%CI: 1.87-4.71, I(2)=51.3%). Meanwhile, the analysis suggested that partial DAZ3/4 deletion was not associated with male infertility risk in East-Asian ethnicity (ORs=1.02, 95%CI: 0.54-1.92, I(2)=71.3%), but not in Non-East Asian under the random effect model (ORs=3.56, 95%CI: 1.13-11.23, I(2)=0.0%,). More interestingly, partial DAZ1/2 deletion was associated with azoospermia (ORs=2.63, 95%CI: 1.19-5.81, I(2)=64.7%) and oligozoospermia (ORs=2.53, 95%CI: 1.40-4.57, I(2)=51.8%), but partial DAZ3/4 deletion was not associated with azoospermia (ORs=0.71, 95%CI: 0.23-2.22, I(2)=71.7%,) and oligozoospermia (ORs=1.21, 95%CI: 0.65-2.24, I(2)=55.5%). In our meta-analysis, partial DAZ1/2 deletion is a risk factor for male infertility and different ethnicities have different influences, whereas partial DAZ3/4 deletion has no effect on fertility but partial DAZ3/4 deletion might have an impact on Non-East Asian male.