Shengming Dai

Diagnostic Value of the Combination of Golgi Protein 73 and Alpha-Fetoprotein in Hepatocellular Carcinoma: A Meta-Analysis

Conflicting results have been widely reported on the use of Golgi protein 73 (GP73) as a serum biomarker for diagnosing hepatocellular carcinoma (HCC). This study evaluated the accuracy of GP73, alpha-fetoprotein (AFP), and GP73 + AFP for diagnosing HCC. The meta-analysis was performed on 11 studies that were selected by means of a comprehensive systematic literature review. Summary diagnostic accuracy, meta-regression analysis for heterogeneity and publication bias, and other statistical analyses were performed using Meta-Disc (version 1.4) and Stata (version 12.0). Pooled sensitivity, specificity, and diagnostic odds ratio were 0.77 (95% CI: 0.75–0.79), 0.91 (95% CI: 0.90–0.92), and 12.49 (95% CI: 4.91–31.79) for GP73; 0.62 (95% CI: 0.60–0.64), 0.84 (95% CI: 0.83–0.85), and 11.61 (95% CI: 8.02–16.81) for AFP; and 0.87 (95% CI: 0.85–0.89), 0.85 (95% CI: 0.84–0.86), and 30.63 (95% CI: 18.10–51.84) for GP73 + AFP. The area under the curve values were 0.86, 0.84, and 0.91 for GP73, AFP, and GP73 + AFP, respectively. These results indicate that for HCC diagnosis, the accuracy of GP73 was higher than that of AFP, and that GP73 + AFP exhibited significantly higher diagnostic accuracy than did GP73 or AFP alone.

Meta-signature LncRNAs serve as novel biomarkers for colorectal cancer: integrated bioinformatics analysis, experimental validation and diagnostic evaluation

The aim of this study is to explore the differentially expressed lncRNAs, which may have potential biological function and diagnostic value in colorectal cancer (CRC). Through integrated data mining, we finally identified nine differentially expressed lncRNAs and their potential mRNA targets. After a series of bioinformatics analyses, we screened significant pathways and GO terms that are related to the up-regulated and down-regulated transcripts respectively. Meanwhile, the nine lncRNAs were validated in 30 paired tissues and cell lines by qRT-PCR and the results were basically consistent with the microarray data. We also tested the nine lncRNAs in the serum of 30 CRC patients matched with the CRC tissue, 30 non-cancer patients and 30 health controls. Finally, we found that BLACAT1 was significant for the diagnosis of CRC. The area under the curve (AUC), sensitivity and specificity were 0.858 (95% CI: 0.765–0.951), 83.3% and 76.7% respectively between CRC patients and health controls. Moreover, BLACAT1 also had distinct value to discriminate CRC from other non-cancer diseases. The results indicated that the differentially expressed lncRNAs and their potential target transcripts could be considered as potential therapeutic targets for CRC patients. Meanwhile, lncRNA BLACAT1 might represent a new supplementary biomarker for the diagnosis of CRC.

Interleukin-6 Levels in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Background The change of serum interleukin-6(IL-6) levels in women with polycystic ovary syndrome (PCOS), as well as the relations between IL-6 levels and body mass index (BMI), insulin resistance(IR) and androgen status of PCOS patients, are not fully understood. Methods A literature search was performed in October 2015 using PubMed, Embase and the Cochrane Library databases to identify studies. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results Twenty articles with 25 case-control studies included 1618 women (922 PCOS patients and 696 controls) were included in this study. IL-6 levels in controls were significantly lower than that of PCOS patients (SMD = 0.78, 95%CI = 0.41–1.16, P<0.001), with significant heterogeneity across studies (I2 = 91% and P<0.001). Meta-regression analysis model indicated IR status was the main source of heterogeneity (P = 0.005). Results from group analysis suggested that high IL-6 levels in PCOS were significantly associated with Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR) ratio and total testosterone ratio (T ratio), and was found in both lean and obese women with PCOS. Cumulative meta-analysis results indicated the total effect size (SMD) had tend to be stable since 2012(0.79 to 0.92). Conclusions A high IL-6 level is not an intrinsic characteristic of PCOS, but may be a useful monitoring biomarker for the treatment of PCOS.

Association between High Serum Homocysteine Levels and Biochemical Characteristics in Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

Background Elevated homocysteine levels have been observed in previous studies of PCOS; however, the nature of the associations between high homocysteine levels and the biochemical characteristics of polycystic ovarian syndrome (PCOS)—such as obesity, insulin resistance (IR), and androgen levels—is still uncertain. Methods A systematic search was conducted electronically up to December 28, 2015 using specific eligibility criteria. Standardized mean difference (SMD) and the corresponding 95% confidence intervals (95% CIs) were used as a measure of effect size. Results A total of 34 studies (with 1,718 cases and 1,399 controls) of homocysteine levels in PCOS were pooled in this meta-analysis. Significantly lower homocysteine levels were found in controls than in PCOS patients (SMD = 0.895, 95% CI = 0.643–1.146, P<0.001; I2 = 90.4% and P<0.001 for heterogeneity), regardless of the degree of obesity, IR, or androgen levels. Homocysteine levels in non-IR PCOS patients were significantly lower than those of PCOS patients with IR (SMD = 0.69, 95% CI = 0.37–1.01, P<0.01; I2 = 0% and P = 0.50 for heterogeneity). However, metformin treatment did not appear to cause any significant change in the homocysteine levels of PCOS patients (SMD = –0.17, 95% CI = –1.10–0.75, P = 0.71; I2 = 92% and P<0.01 for heterogeneity). Conclusions High homocysteine levels in women with PCOS are not related to degree of obesity, IR, or androgen levels. Metformin treatment cannot decrease the homocysteine levels in PCOS patients.

Diagnostic value of circulating miR-21: An update meta-analysis in various cancers and validation in endometrial cancer

MiR-21 has been identified as one of the most common proto-oncogenes. It is hypothesized that up-regulated miR-21 could be served as a potential biomarker for human cancer diagnosis. However, inconsistencies or discrepancies about diagnostic accuracy of circulating miR-21 still remain. In this sense, miR-21′s diagnostic value needs to be fully validated. In this study, we performed an update meta-analysis to estimate the diagnostic value of circulating miR-21 in various human cancers. Additionally, we conducted a validation test on 50 endometrial cancer patients, 50 benign lesion patients and 50 healthy controls. A systematical literature search for relevant articles was performed in Pubmed, Embase and Cochrane Library. A total of 48 studies from 39 articles, involving 3,568 cancer patients and 2,248 controls, were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.76 (0.71-0.80), 0.82 (0.79-0.85), 4.3 (3.6-5.1), 0.29 (0.24-0.35), 15 (11-20) and 0.86 (0.83-0.89), respectively. In the validation test, the expression levels of serum miR-21 were significantly higher in benign lesion patients (p = 0.003) and endometrial cancer patients (p = 0.000) compared with that of healthy controls. Endometrial cancer patients showed higher miR-21 expression levels (p = 0.000) compared with benign lesion patients. In conclusion, the meta-analysis shows that circulating miR-21 has excellent performance on the diagnosis for various cancers and the validation test demonstrates that serum miR-21 could be served as a novel biomarker for endometrial carcinoma.

Hec1 inhibition alters spindle morphology and chromosome alignment in porcine oocytes

Aneuploidy is caused by incorrect chromosome segregation and can result in cancer or birth defects. The spindle assembly checkpoint (SAC) guarantees proper cell cycle progression. Highly Expressed in Cancer protein 1 (Hec1, also called Ndc80) is the core component of the Ndc80 complex and is involved in regulating both kinetochore-microtubule interactions and the SAC during mitosis in multiple cell types. However, its involvement in pig oocyte meiotic maturation remains uncertain. Thus, we investigated Hec1 expression, localization, and possible functions during porcine oocyte meiosis. Immunofluorescent staining showed that Hec1 was expressed in porcine oocytes and was associated with centromeres at both the metaphase I and metaphase II stages. Disrupting Hec1 function with its inhibitor INH1 resulted in polar body extrusion defects in porcine oocytes. Moreover, inhibiting Hec1 activity also resulted in severe chromosome misalignments and aberrant spindle morphology. Our results showed a unique localization pattern for Hec1 in porcine oocytes and suggested that Hec1 was required for chromosome alignment and spindle organization. Thus, Hec1 might regulate spindle checkpoint activity during mammalian oocyte meiosis.

Diagnosis, prognosis and bioinformatics analysis of lncRNAs in hepatocellular carcinoma

This study aims to comprehensively analyze the diagnosis and prognosis of lncRNAs in hepatocellular carcinoma (HCC). From the Gene Expression Omnibus database, we screened out and analyzed the differently expressed lncRNAs and related mRNAs using bioinformatics methods. The expressions of lncRNAs were validated in tumor tissues, cell lines and the Cancer Genome Atlas database. At the same time, we also conducted an exploratory analysis on the diagnostic and prognostic ability of lncRNAs in HCC. In this study, we found that most of the targeted mRNAs promote the biological process of cell division, cellular component of nucleoplasm, molecular function of protein binding, which were significantly associated with 12 KEGG pathways. LncRNA CRNDE and LINC01419 also had significant diagnostic value in HCC. In particular, the sensitivity, specificity and area under the curve of CRNDE were 71.0%, 87.1% and 0.701 (95% CI: 0.543-0.860), respectively. In addition, the high expression of CRNDE and GBAP1 predicated poor prognosis, while the high expression of LINC01093 suggested the opposite outcome. Through the comprehensive analysis of lncRNAs, it provided an important reference for the early diagnosis, prognosis evaluation, pathogenesis and targeted therapy of HCC.

Integrated analysis of the potential roles of miRNA‑mRNA networks in triple negative breast cancer

Triple negative breast cancer (TNBC) is a type of breast cancer where the tumor cells are negative for the estrogen, progesterone and human epidermal growth factor 2 receptors. To date, expression profiling of microRNA (miRNA/miR) and mRNA sequences have been widely applied for the diagnosis of TNBC. In the present study, an integrated analysis of miRNA-mRNA profiling arrays was performed. A total of five dysregulated miRNAs in patients with TNBC were identified, including upregulated miR-558 expression and downregulated miR-320d-1, miR-548v, miR-99a and miR-21 expression. In addition, 49 potential target mRNA sequences were identified. Bioinformatics analyses were performed on the identified miRNAs and mRNAs, including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway and miRNA-mRNA network analyses. A total of 31 GO terms and three signaling pathways were identified. The results indicated that the differentially expressed miRNAs and their potential target mRNAs may affect the pathogenesis of TNBC, and may therefore be considered as promising biomarkers for the early diagnosis and targeted therapy of patients with TNBC.

Diagnostic accuracy of osteopontin plus alpha-fetoprotein in the hepatocellular carcinoma: A meta-analysis

OBJECTIVE Osteopontin (OPN) has been reported as a potential biomarker for diagnosis of hepatocellular carcinoma (HCC) in many inconsistent results. This study demonstrates a systematic meta-analysis for the evaluation on diagnostic accuracy of serum or plasma OPN and alpha-fetoprotein (AFP) alone and combined assays for HCC. METHODS Relevant literatures were searched in PubMed up to August 2016. The quality of each study was evaluated by QUADAS-2 (quality assessment for studies of diagnostic accuracy). Statistical analysis was performed by Meta-Disc 1.4 and Stata 12.0. The random-effect models were used to estimate pooled sensitivity, specificity and other diagnostic indicators of OPN and/or AFP in HCC. RESULTS A total of 14 case-control literatures (15 studies) met the inclusion criteria in this meta-analysis. The respective pooled diagnostic sensitivity and specificity were 0.71 (95% CI: 0.69-0.74) and 0.80 (95% CI: 0.78-0.82) for OPN; 0.61 (95% CI: 0.58-0.63) and 0.92 (95% CI: 0.91-0.94) for AFP; 0.82 (95% CI: 0.79-0.84) and 0.77 (95% CI: 0.74-0.80) for OPN plus AFP. Their area under the curve (AUC) values were 0.8786, 0.8718 and 0.9005, respectively. CONCLUSION Combination of OPN and AFP was better than OPN or AFP alone in diagnosis of HCC.

sTLR4/MD-2 complex inhibits colorectal cancer in vitro and in vivo by targeting LPS

Colorectal cancer (CRC) is aggressive and associated with TLR4-MD-2 signaling. Toll-like receptor 4 (TLR4) and myeloid differentiation protein 2 (MD-2) were highly expressed in human CRC. The soluble form of extracellular TLR4 domain (sTLR4) and MD-2 may have important roles in binding lipopolysaccharide (LPS). In this study, sTLR4 and MD-2 protein and prepared sTLR4/MD-2 complex were synthesized successfully to restrain LPS-TLR4/MD-2 activation by competing with cellular membrane TLR4 for binding LPS. The sTLR4/MD-2 complex can significantly attenuate LPS induced pro-inflammatory and migration cytokine production in vitro and in vivo, and inhibit the effect of LPS on the cell cycle, migration and invasion of human CRC cells in vitro. Administration of sTLR4/MD-2 complex protected mice from tumor both in xenograft and implantation metastasis model. The sTLR4/MD-2 complex treated mice had smaller tumor, less body weight loss and lower expression of inflammatory cytokines. Here, the azoxymethane/dextran sulfate sodium salt (AOM/DSS) murine model was used as an experimental platform to simulate the physiological and pathological processes of cancers associated with chronic intestinal inflammation. AOM/DSS-induced tumors were inhibited in mice treated by sTLR4/MD-2 complex. It is demonstrated in our study that sTLR4/MD-2 complex could inhibit CRC by competing with binding LPS, raising the complexs possibility of a new prevention agent against CRC.