Clinical Implication of E2F Transcription Factor 1 in Hepatocellular Carcinoma Tissues.

Background: To date, the clinical management of advanced hepatocellular carcinoma (HCC) patients remains challenging and the mechanisms of E2F transcription factor 1 (E2F1) underlying HCC are obscure. Materials and Methods: Our study integrated datasets mined from several public databases to comprehensively understand the deregulated expression status of E2F1. Tissue microarrays and immunohistochemistry staining was used to validate E2F1 expression level. The prognostic value of E2F1 was assessed. In-depth subgroup analyses were implemented to compare the differentially expressed levels of E2F1 in HCC patients with various tumor stages. Functional enrichments were used to address the predominant targets of E2F1 and shedding light on their potential roles in HCC. Results: We confirmed the elevated expression of E2F1 in HCC. Subgroup analyses indicated that elevated E2F1 level was independent of various stages in HCC. E2F1 possessed moderate discriminatory capability in differentiating HCC patients from non-HCC controls. Elevated E2F1 correlated with Asian race, tumor classification, neoplasm histologic grade, eastern cancer oncology group, and plasma AFP levels. Furthermore, high E2F1 correlated with poor survival condition and pooled HR signified E2F1 as a risk factor for HCC. Enrichment analysis of differentially expressed genes, coexpressed genes, and putative targets of E2F1 emphasized the importance of cell cycle pathway, where CCNE1 and CCNA2 served as hub genes. Conclusions: We confirmed the upregulation of E2F1 and explored the prognostic value of E2F1 in HCC patients. Two putative targeted genes (CCNE1 and CCNA2) of E2F1 were identified for their potential roles in regulating cell cycle and promote antiapoptotic activity in HCC patients.

CCNB1 promotes the development of hepatocellular carcinoma by mediating DNA replication in the cell cycle.

In our studies, cyclin B1 (CCNB1) mRNA and protein were overexpressed in hepatocellular carcinoma (HCC) tissues compared with non-HCC tissues. Moreover, CCNB1 was overexpressed in the serum of HCC patients. The expression of CCNB1 was associated with several crucial clinicopathologic characteristics, and the HCC patients with overexpressed CCNB1 had worse overall survival outcomes. In the screening of interactional genes, a total of 266 upregulated co-expression genes, which were positively associated with CCNB1, were selected from the datasets, and 67 downregulated co-expression genes, which were negatively associated with CCNB1, were identified. The key genes might be functionally enriched in DNA replication and the cell cycle pathways. CDC20, CCNA2, PLK1, and FTCD were selected for further research because they were highly connected in the protein-protein interaction networks. Upregulated CDC20, CCNA2, and PLK1 and downregulated FTCD might result in undesirable overall survival outcomes for HCC patients. The univariate Cox analysis results showed that CDC20 and PLK1 might be two independent risk factors, while FTCD might be protective in HCC. Therefore, CCNB1 may participate in the cell cycle of HCC by regulating DNA replication, and CCNB1 may provide a direction for the diagnosis of early-stage HCC and targeted HCC therapy.

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis.

BACKGROUND: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. METHODS: Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. RESULTS: COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. CONCLUSIONS: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.

The clinical significance of interleukin 24 and its potential molecular mechanism in laryngeal squamous cell carcinoma.

Interleukin 24 (IL24) has been documented to be highly expressed in several cancers, but its role in laryngeal squamous cell carcinoma (LSCC) remains unclarified. In this study, to reveal the function and its clinical significance of IL24 in LSCC, multiple detecting methods were used comprehensively. IL24 protein expression was remarkably higher in LSCC (n= 49) than non-cancerous laryngeal controls (n= 26) as detected by in-house immunohistochemistry. Meanwhile, the IL24 mRNA expression was also evaluated based on high throughput data from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress and Oncomine databases. Consistently with the protein level, IL24 mRNA expression level was also predominantly upregulated in LSCC (n= 172) compared to non-cancerous laryngeal tissues (n= 81) with the standard mean difference (SMD) being 1.25 and the area under the curve (AUC) of the summary receiver operating characteristic (sROC) being 0.89 (95% CI = 0.86-0.92). Furthermore, the related genes of IL24 and the differentially expressed genes (DEGs) of LSCC were intersected and sent for Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the protein-protein interaction (PPI) analyses. In the GO annotation, the top terms of biological process (BP), cellular component (CC) and molecular function (MF) were extracellular matrix organization, extracellular matrix, cytokine activity, respectively. The top pathway of KEGG was ECM-receptor interaction. The PPI networks indicated the top hub genes of IL24-related genes in LSCC were SERPINE1, TGFB1, MMP1, MMP3, CSF2, and ITGA5. In conclusion, upregulating expression of IL24 may enhance the occurrence of LSCC, which owns prospect diagnostic ability and therapeutic significance in LSCC.

Identification of an Immune Score-Based Gene Panel with Prognostic Power for Oral Squamous Cell Carcinoma.

BACKGROUND Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer worldwide, with low 5-year survival rate. To identify novel prognostic markers for OSCC and determine the immune and stromal landscape of OSCC, a risk signature for OSCC patients was constructed in this study. MATERIAL AND METHODS Immune and stromal scores for OSCC samples from the Genomic Data Commons Data Portal were computed to delineate the tumor microenvironment landscape of oral cancer based on the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data algorithm. An immune score-based risk signature was constructed by combining random forest and support vector machine methods. Correlation analysis of risk signature gene expression and immune cell infiltration was conducted, and the distinguishing power of individual signature genes was evaluated by analyzing receiver operating characteristics (ROC) curves. Differentially enriched pathways between high and low risk groups were investigated via gene set variation analysis. ROC curves were plotted for signature genes to examine their ability to distinguish the recurrence and survival status of OSCC patients from GSE84846. RESULTS An immune score-related risk signature composed of ARMH1, F2RL2, AC004687.1, COL6A5, AC008750.1, RAB19, CRLF2, GRIP2, and FAM162B performed well in the prognostic stratification of OSCC patients and could effectively distinguish their survival status. Lists of pathways, including cytokine-cytokine receptor interaction and cell adhesion molecules displayed remarkable differential enrichment between high and low risk OSCC patients. CONCLUSIONS An immune score-based risk signature constructed presently may be useful to decide appropriate treatment options for individual OSCC patients.

Clinicopathological value and underlying molecular mechanism of annexin A2 in 992 cases of thyroid carcinoma.

BACKGROUND: Thyroid carcinoma (THCA) is one of the most frequent endocrine cancers and has increasing morbidity. Annexin A2 (ANXA2) has been found to be highly expressed in various cancers; however, its expression level and potential mechanism in THCA remain unknown. This study investigated the clinicopathological value and primary molecular machinery of ANXA2 in THCA. MATERIAL AND METHODS: Public RNA-sequencing and microarray data were obtained and analyzed with ANXA2 expression in THCA and corresponding non-cancerous thyroid tissue. A Pearson correlation coefficient calculation was used for the acquisition of ANXA2 coexpressed genes, while edgR, limma, and Robust Rank Aggregation were employed for differentially expressed gene (DEG) in THCA. The probable mechanism of ANXA2 in THCA was predicted by gene ontology and pathway enrichment. A dual-luciferase reporter assay was employed to confirm the targeting relationships between ANXA2 and its predicted microRNA (miRNA). RESULTS: Expression of ANXA2 was significantly upregulated in THCA tissues with a summarized standardized mean difference of 1.09 (P < 0.0001) based on 992 THCA cases and 589 cases of normal thyroid tissue. Expression of ANXA2 was related to pathologic stage. Subsequently, 1442 genes were obtained when overlapping 4542 ANXA2 coexpressed genes with 2248 DEGs in THCA; these genes were mostly enriched in pathways of extracellular matrix-receptor interaction, cell adhesion molecules, and complement and coagulation cascades. MiR-23b-3p was confirmed to target ANXA2 by dual-luciferase reporter assay. CONCLUSIONS: Upregulated expression of ANXA2 may promote the malignant biological behavior of THCA by affecting the involving pathways or being targeted by miR-23b-3p.

Identification of prognostic splicing factors and exploration of their potential regulatory mechanisms in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD), the most common subtype of pancreatic cancer, is a highly lethal disease. In this study, we integrated the expression profiles of splicing factors (SFs) of PAAD from RNA-sequencing data to provide a comprehensive view of the clinical significance of SFs. A prognostic index (PI) based on SFs was developed using the least absolute shrinkage and selection operator (LASSO) COX analysis. The PI exhibited excellent performance in predicting the status of overall survival of PAAD patients. We also used the percent spliced in (PSI) value obtained from SpliceSeq software to quantify different types of alternative splicing (AS). The prognostic value of AS events was explored using univariate COX and LASSO COX analyses; AS-based PIs were also proposed. The integration of prognosis-associated SFs and AS events suggested the potential regulatory mechanisms of splicing processes in PAAD. This study defined the markedly clinical significance of SFs and provided novel insight into their potential regulatory mechanisms.

The role of upregulated miR-375 expression in breast cancer: An in vitro and in silico study.

Breast cancer (BC) is the most common cancer worldwide. However, the expression and potential mechanism of miR-375 in BC are still controversial. We first collected microRNA chips and microRNA sequencing data from multiple databases for analyzing the expression level of miR-375, and further exploring the target genes and underlying molecular mechanism in BC. miR-375 in BC was predominantly overexpressed compared with that in normal breast tissues (pooled standard mean difference [SMD] = 0.49; 95 % confidence interval [CI]: 0.24-0.73, p < 0.0001). Meanwhile, the overall pooled area under the curve (AUC) in the summary receiver operating characteristic (SROC) of miR-375 was 0.83 (95 % CI = 0.79-0.86) based on 2928 cases of BC patients and 816 cases of controls, while the diagnostic positive likelihood ratio (DLR) positive and the DLR negative value were 3.90 (95 % CI = 2.46-6.19) and 0.39 (95 % CI = 0.28-0.54), respectively. The hazard ratios (HRs) were 1.29 (95 % CI = 1.04-1.6, P = 0.02) and 1.23 (95 % CI = 0.89-1.7, P = 0.22) for the cohorts of METABRIC and The Cancer Genome Atlas (TCGA). In vitro study demonstrated that miR-375 inhibitor could suppress the cell growth and induce apoptosis of BC cells. A total of 107 overlapping genes from microarrays after miR-375 transfection, the TCGA RNA sequencing, the microarrays of Affymetrix platform, and online predicting software were selected as the prospective targets of miR-375 in BC. Based on Gene Ontology (GO) enrichment analysis, the potential targets of miR-375 were notable for their somatic stem cell division, plasma membrane, and proline-rich region binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway examination demonstrated that the targets were associated with the pathways of prion diseases, proteoglycans in cancer, and focal adhesion. Then, 107 targets of miR-375 in BC were used to construct a protein-protein interaction (PPI) network. Finally, EGFR, PRKCA, PPARA, ADIPOQ, and ITSN1 were found to be the hub genes of miR-375. These targets showed negative correlations with miR-375 level. The upregulated miR-375 might play an essential part in the tumorigenesis and progression of BC.

Differentially expressed gene profile and relevant pathways of the traditional Chinese medicine cinobufotalin on MCF­7 breast cancer cells.

Cinobufotalin is a chemical compound extracted from the skin of dried bufo toads that may have curative potential for certain malignancies through different mechanisms; however, these mechanisms remain unexplored in breast cancer. The aim of the present study was to investigate the antitumor mechanism of cinobufotalin in breast cancer by using microarray data and in silico analysis. The microarray data set GSE85871, in which cinobufotalin exerted influences on the MCF­7 breast cancer cells, was acquired from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) were analyzed. Subsequently, protein interaction analysis was conducted, which clarified the clinical significance of core genes, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to analyze cinobufotalin­related pathways. The Connectivity Map (CMAP) database was used to select existing compounds that exhibited curative properties similar to those of cinobufotalin. A total of 1,237 DEGs were identified from breast cancer cells that were treated with cinobufotalin. Two core genes, SRC proto­oncogene non­receptor tyrosine kinase and cyclin­dependent kinase inhibitor 2A, were identified as serving a vital role in the onset and development of breast cancer, and their expression levels were markedly reduced following cinobufotalin treatment as detected by the microarray of GSE85871. It also was revealed that the 'neuroactive ligand­receptor interaction' and 'calcium signaling' pathways may be crucial for cinobufotalin to perform its functions in breast cancer. Conducting a matching search in CMAP, miconazole and cinobufotalin were indicated to possessed similar molecular mechanisms. In conclusion, cinobufotalin may serve as an effective compound for the treatment of a subtype of breast cancer that is triple positive for the presence of estrogen, progesterone and human epidermal growth factor receptor­2 receptors, and its mechanism may be related to different pathways. In addition, cinobufotalin is likely to exert its antitumor influences in a similar way as miconazole in MCF­7 cells.

Overexpression of MiR-452-5p in hepatocellular carcinoma tissues and its prospective signaling pathways.

BACKGROUND: The implication of miR-452-5p and its prospective machinery in hepatocellular carcinoma (HCC) remains largely unknown. For this reason, this study aimed to inspect the clinical implication of miR-452-5p expression in HCC tissues with multiple detection approaches, to analyze its potential function via in silico methods, and to validate this using a dual-luciferase reporter assay. METHODS: The assessment of the expression level of miR-452-5p in HCC was conducted via four methods: 1) in-house real-time quantitative PCR (RT-qPCR), 2) miRNA-sequencing (miRNA-seq) from The Cancer Genome Atlas (TCGA), 3) miRNA microarrays from the Gene Expression Omnibus (GEO), and 4) comprehensive meta-analyses calculating the standard mean difference (SMD) and summary of receiver operator characteristic (sROC). Following the target prediction, one of the potential targets of miR-452-5p was validated through a dual-luciferase reporter assay. RESULTS: MiR-452-5p was consistently elevated in HCC tissues via various detection methods, including in-house RT-qPCR, miRNA-seq, and miRNA microarrays. The final SMD was 0.842 for 820 cases of HCC samples. Simultaneously, the area under curve (AUC) of the sROC was 0.80 (0.76-0.83). The 1,135 predicted targets of miR-452-5p were enriched in the pathways of cytokine-cytokine receptor interaction, carbon metabolism, and complement and coagulation cascades. Among these predicted targets, CDKN1B was verified to be a real target of miR-452-5p. CONCLUSION: The overexpression of miR-452-5p may play a pivotal role in the carcinogenesis of HCC via targeting multiple signaling pathways and genes. The function and molecular machinery of miR-452-5p in HCC requires further in-depth exploration.

High expression of long non­coding HOTAIR correlated with hepatocarcinogenesis and metastasis.

HOX transcript antisense RNA (HOTAIR), a newly discovered long noncoding RNA (lncRNA), has been reported to be a poor prognostic marker in many types of cancers. The current study attempted to investigate the biological roles and clinicopathlogical implications of HOTAIR in hepatocellular carcinoma (HCC), as well as understand the molecular mechanisms of HOTAIR in HCC progression. HOTAIR expression in 95 HCC patients with paired HCC tissues and adjacent non­cancer tissues were investigated using quantitative reverse transcription­polymerase chain reaction. The association between HOTAIR expression and clinicopathological features was assessed. The effects of HOTAIR were examined in vitro assays by silencing the lncRNA. Pathway analyses were performed to illustrate the biological functions of the HOTAIR and coexpression genes. The expression level of HOTAIR was observed significantly higher in the HCC tissue than the adjacent non­tumor tissue. HOTAIR expression levels were significantly higher in tumor samples from patients with distant metastasis, advanced stage, portal vein tumor embolus, vasoinvasion, tumor capsular infiltration or positive nm23 expression than those from patients without these conditions, correspondingly. The silencing of HOTAIR in liver cancer cells induced the inhibition of cell proliferation and promotion of apoptosis. Several pathways such as extracellular matrix­receptor interaction, focal adhesion, pathways in cancer were annotated with the HOTAIR and coexpression genes. In summary, the present analysis indicates that HOTAIR might be an oncogene in HCC. It functions though promoting tumor cell growth and inhibiting apoptosis. HOTAIR may potentially be involved in HCC metastatic progression by several pathways correlated to cell adhesion, and may be a therapeutic target in future.

Promising significance of the association of miR-204-5p expression with clinicopathological features of hepatocellular carcinoma.

Decreased level of miR-204-5p has been documented in various malignancies. However, the expression and clinical significance of miR-204-5p in hepatocellular carcinoma has not been investigated. The aim of this study is to examine the relationship between miR-204-5p expression and clinicopathological features in hepatocellular carcinoma (HCC) as well as to predict the relevant signaling pathways. The miR-204-5p expression level was detected in HCC and in matched paraneoplastic liver from 95 formalin-fixed paraffin-embedded tissues by the real-time reverse transcription polymerized chain reaction (qRT-PCR). The association of miR-204-5p expression with clinicopathological features as well as the prognosis of HCC was examined. Public data portals including the Gene Expression Omnibus and The Cancer Genome Atlas were used to retrieve the HCC-related data in order to perform a comprehensive meta-analysis. Meanwhile, protein-protein interaction (PPI) and enrichment analyses were performed using predicted target genes. The relative expression of miR-204-5p was remarkably reduced in HCC than that in paraneoplastic hepatic tissues. In HCC, the miR-204-5p expression was downregulated in the metastasis, vasoinvasion, and advanced stage (III and IV) subgroups compared with their counterparts. Furthermore, the meta-analysis based on qRT-PCR data demonstrated that miR-204-5p was markedly downregulated in HCC with a standardized mean difference of -5.19 (P < .001). However, no significant association was observed between miR-204-5p and survival outcomes. The potential target genes of miR-204-5p were significantly enriched in several pathways which might be associated with HCC, such as "cell proliferation" from GO terms and "pathways in cancer" from the KEGG analysis. A PPI network of miR-204-5p potential target genes identified prospective core genes potentially involved in the regulation of HCC oncogenesis and progression. Our findings suggested that miR-204-5p might act as a tumor-suppressive gene in the tumorigenesis and progression of HCC via vital signaling pathways and that miR-204-5p could be regarded as a protective factor in HCC.

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.

Anisotropic patterns of liver cancer prevalence in Guangxi in Southwest China: is local climate a contributing factor?

Geographic information system (GIS) technology has useful applications for epidemiology, enabling the detection of spatial patterns of disease dispersion and locating geographic areas at increased risk. In this study, we applied GIS technology to characterize the spatial pattern of mortality due to liver cancer in the autonomous region of Guangxi Zhuang in southwest China. A database with liver cancer mortality data for 1971-1973, 1990-1992, and 2004-2005, including geographic locations and climate conditions, was constructed, and the appropriate associations were investigated. It was found that the regions with the highest mortality rates were central Guangxi with Guigang City at the center, and southwest Guangxi centered in Fusui County. Regions with the lowest mortality rates were eastern Guangxi with Pingnan County at the center, and northern Guangxi centered in Sanjiang and Rongshui counties. Regarding climate conditions, in the 1990s the mortality rate of liver cancer positively correlated with average temperature and average minimum temperature, and negatively correlated with average precipitation. In 2004 through 2005, mortality due to liver cancer positively correlated with the average minimum temperature. Regions of high mortality had lower average humidity and higher average barometric pressure than did regions of low mortality. Our results provide information to benefit development of a regional liver cancer prevention program in Guangxi, and provide important information and a reference for exploring causes of liver cancer.

Effects of miR-152 on cell growth inhibition, motility suppression and apoptosis induction in hepatocellular carcinoma cells.

BACKGROUND: miR-152 is involved in the genesis and development of several malignancies. However, its role in HCC has not been fully clarified. The aim of this study was to investigate the clinicopathological significance of miR-152 and its effect on the malignant phenotype of HCC cells. METHODS: miR-152 expression was detected using real-time quantitative RT-PCR in 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissues. Functionally, in vitro effects and mechanisms of action of miR-152 on proliferation, viability, caspase activity, apoptosis and motility were explored in HepG2, HepB3 and SNU449 cells, as assessed by spectrophotometry, fluorimetry, fluorescence microscopy, wound-healing and Western blotting, respectively. RESULTS: miR-152 expression in HCC was downregulated remarkably compared to that in adjacent hepatic tissues. miR-152 levels in groups of advanced clinical stage, larger tumor size and positive HBV infection, were significantly lower than in other groups. A miR-152 mimic could suppress cell growth, inhibit cell motility and increase caspase activity and apoptosis in HCC cell lines. Furthermore, Western blotting showed that the miR-152 mimic downregulated Wnt-1, DNMT1, ERK1/2, AKT and TNFRS6B signaling. Intriguingly, inverse correlation of TNFRF6B and miR-152 expression was found in HCC and bioinformatics confirmed that TNFRF6B might be a target of miR- 152. CONCLUSIONS: Underexpression of miR-152 plays a vital role in hepatocarcinogenesis and lack of miR-152 is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis. miR-152 may act as a tumor suppressor miRNA by also targeting TNFRSF6B and is therefore a potential candidate biomarker for HCC diagnosis, prognosis and molecular therapy.

Expression of tumor necrosis factor receptor-associated factor 6 in lung cancer tissues.

BACKGROUND: Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) has been reported to be associated with the development of various cancers. However, the role of TRAF6 in lung cancer remains unclear. OBJECTIVE: To explore the expression and clinicopathological significance of TRAF6 protein in lung cancer tissues. MATERIALS AND METHODS: Three hundred and sixty-five lung cancer samples and thirty normal lung tissues were constructed into 3 microarrays. The expression of TRAF6 protein was determined using immunohistochemistry (IHC). Furthermore, correlations between the expression of TRAF6 and clinicopathological parameters were investigated. RESULTS: The expression of TRAF6 in total lung cancer tissues (365 cases), as well as in small cell lung cancer (SCLC, 26 cases) and non-small cell lung cancer (NSCLC, 339 cases) was significantly higher compared with that in normal lung tissues. The ROC curve showed that the area under curve of TRAF6 was 0.663 (95%CI 0.570~0.756) for lung cancer. The diagnostic sensitivity and specificity of TRAF6 were 52.6% and 80%, respectively. In addition, the expression of TRAF6 was correlated with clinical TNM stage, tumor size and lymph node metastasis in all lung cancers. Consistent correlations were also observed for NSCLCs. CONCLUSIONS: TRAF6 might be an oncogene and the expression of TRAF6 protein is related to the progression of lung cancer. Thus, TRAF6 might become a target for diagnosis and gene therapy for lung cancer patients.

Lack of significant association between plasma/serum miR-221 expression and poor survival of carcinoma: a meta-analysis.

Background. MicroRNAs (miRNAs) exhibit altered expression levels in cancers, and they may play a potential role as diagnostic and prognostic biomarkers of cancers. The aim of this meta-analysis was to summarize recent advances in miR-221 involvement in a variety of carcinomas and derive a more precise estimation of the relationship between circulating miR-221 level and survival of cancer patients. Methods. We searched online PubMed, EMBASE, and Cochrane Library up to August 2013 to identify relevant studies. Data were collected from studies comparing survival in patients with various carcinomas with higher miR-221 expression to those with lower levels. Pooled hazard ratios (HRs) of miR-221 for survival were calculated. Results. There were 4 studies included in the meta-analysis. The results of meta-analysis suggested that no significant difference in poor overall survival between miR-221 high and low groups (OR = 0.94, 95%, CI = 0.47-1.87, Z = 0.17, and P = 0.863). Conclusions. The current meta-analysis showed the equivalence of high and low plasma/serum miR-221 expression for carcinomas in terms of survival.