Construction and validation of a prognostic model of pyroptosis related genes in hepatocellular carcinoma.

Pyroptosis plays an important role in the occurrence and development of cancer. We are interested in determining the prognostic value of pyroptosis-related genes in hepatocellular carcinoma (HCC). In this study, we searched the original transcriptome data of The Cancer Genome Atlas (TCGA) and identified the related expressed genes by co-expression analysis. Differentially expressed genes were identified by using univariate analysis, the least absolute shrinkage and selection operator (LASSO) and multivariate analysis to screen for genes related to prognosis of HCC. Ultimately, we established a prognostic model for five genes, namely GSDME, DHX9, TREM2, SQSTM1 and GLMN. Survival analysis showed that the overall survival rate of HCC patients with high risk score was significantly lower than that of HCC patients with low risk score, and this signal could be used as an independent prognostic indicator of HCC. Receiver operating characteristic curve analysis confirmed the accuracy of this prognostic signal, and was further verified in a Gene Expression Omnibus (GEO) dataset (GSE14520) and the International Cancer Genome Consortium (ICGC) databases. In addition, nomograms based on the five identified prognostic genes were established and verified internally in TCGA cohort. Additionally, we also analyzed the gene mutations of the model genes and the correlation between immune cells of the model genes. In summary, this study identified for the first time a 5-gene prognostic signature associated with pyroptosis, which can be used as a promising prognostic biomarker and provide some potentially useful therapeutic targets for HCC.

Landscape of somatic alterations in large-scale solid tumors from an Asian population.

Extending the benefits of tumor molecular profiling for all cancer patients requires a comprehensive analysis of tumor genomes across distinct patient populations worldwide. In this study, we perform deep next-generation DNA sequencing (NGS) from tumor tissues and matched blood specimens from over 10,000 patients in China by using a 450-gene comprehensive assay, developed and implemented under international clinical regulations. We perform a comprehensive comparison of somatically altered genes, the distribution of tumor mutational burden (TMB), gene fusion patterns, and the spectrum of various somatic alterations between Chinese and American patient populations. Here, we show 64% of cancers from Chinese patients in this study have clinically actionable genomic alterations, which may affect clinical decisions related to targeted therapy or immunotherapy. These findings describe the similarities and differences between tumors from Chinese and American patients, providing valuable information for personalized medicine.

Learning curve for a surgeon in robotic pancreaticoduodenectomy through a "G"-shaped approach: A cumulative sum analysis.

BACKGROUND: Robotic pancreaticoduodenectomy (RPD) can achieve similar surgical results to open and PD; however, RPD has a long learning curve and operation time (OT). To address this issue, we have summarized a surgical path to shorten the surgical learning curve and OT. AIM: To investigate the effective learning curve of a "G"-shaped surgical approach in RPD for patients. METHODS: A total of 60 patients, who received "G"-shaped RPD (GRPD) by a single surgeon in the First Hospital of Shanxi Medical University from May 2017 to April 2020, were included in this study. The OT, demographic data, intraoperative blood loss, complications, hospitalization time, and pathological results were recorded, and the cumulative sum (CUSUM) analysis was performed to evaluate the learning curve for GRPD. RESULTS: According to the CUSUM analysis, the learning curve for GRPD was grouped into two phases: The early and late phases. The OT was 480 ± 81.65 min vs 331 ± 76.54 min, hospitalization time was 22 ± 4.53 d vs 17 ± 6.08 d, and blood loss was 308 ± 54.78 mL vs 169.2 ± 35.33 mL in the respective groups. Complications, including pancreatic fistula, bile leakage, reoperation rate, postoperative death, and delayed gastric emptying, were significantly decreased after this surgical technique. CONCLUSION: GRPD can improve the learning curve and operative time, providing a new method for shortening the RPD learning curve.

Identification and Validation of a Pyroptosis-Related Prognostic Model for Gastric Cancer.

Pyroptosis is an inflammatory form of programmed cell death triggered by caspase-1/4/5/11 that plays an important role in the occurrence and development of gastric cancer (GC). We investigated the prognostic value of pyroptosis-related genes in GC. The "LIMMA" R package and univariate Cox analysis were used to find pyroptosis-related genes with differential expression and prognostic value in the TCGA cohort and the identified genes were analyzed for GO enrichment and KEGG pathways. The selected genes were then included in a multivariate Cox proportional hazard regression analysis, and a ten genes prognostic model (BIRC2, CD274, IRGM, ANXA2, GBP5, TXNIP, POP1, GBP1, DHX9, and TLR2) was established. To evaluate the predictive value of the risk score on prognosis, patients were divided into high-risk and low-risk groups according to the median risk score, and survival analysis was carried out. Compared with the low-risk group, the OS of GC patients in the high-risk group was significantly worse. Additionally, these results were verified in the GSE84437 and GSE66229 datasets. Finally, through the combination of prognostic gene characteristics and clinicopathological features, a nomogram was established to predict individual survival probability. The results show that the genetic risk characteristics related to clinical features can be used as independent prognostic indicators for patients with GC. In summary, the pyroptosis-related risk signals proposed in this study can potentially predict the prognosis of patients with GC. In addition, we also found significant infiltration of dendritic cells, macrophages, and neutrophils in tissues of high-risk patients.

The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles.

BACKGROUND AND AIMS: Long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is aberrantly expressed in various cancers and associated with cancer progression. A comprehensive meta-analysis was performed based on published literature and data in the Gene Expression Omnibus database, and then the Cancer Genome Atlas (TCGA) dataset was used to assess the clinicopathological and prognostic value of FOXD2-AS1 in cancer patients. METHODS: Gene Expression Omnibus databases of microarray data and published articles were used for meta-analysis, and TCGA dataset was also explored using the GEPIA analysis program. Hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the role of FOXD2-AS1 in cancers. RESULTS: This meta-analysis included 21 studies with 2391 patients and 25 GEO datasets with 3311 patients. The pooled HRs suggested that highly expressed FOXD2-AS1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS). Similar results were obtained by analysis of TCGA data for 9502 patients. The pooled results also indicated that FOXD2-AS1 expression was associated with bigger tumor size and advanced TNM stage, but was not related to age, gender, differentiation and lymph node metastasis. CONCLUSION: The present study demonstrated that FOXD2-AS1 is closely related to tumor size and TNM stage. Additionally, increased FOXD2-AS1 was a risk factor of OS and DFS in cancer patients, suggesting FOXD2-AS1 may be a potential biomarker in human cancers.

Long Noncoding RNA LINC00265 Targets EGFR and Promotes Deterioration of Colorectal Cancer: A Comprehensive Study Based on Data Mining and in vitro Validation.

BACKGROUND: LncRNAs are found to be aberrantly expressed in human cancers and could function as potential oncogenes or tumor suppressor genes. LINC00265 is a newly discovered LncRNA and its function in colorectal cancer (CRC) remains unknown. METHODS: Comprehensive bioinformatics analysis were performed to investigate the expression, clinical significance and potential biologic functions of LINC00265 in CRC based on the data from the Cancer Genome Atlas (TCGA). To further investigate the potential role of LINC00265 in CRC, we knocked down the LINC00265 expression in HT29 cells. The cell proliferation, invasion, cycle distribution, and apoptosis were evaluated in control, NC and siRNA groups. Additionally, effect of LINC00265 on the expression of EGFR was also measured. RESULTS: The expression level of LINC00265 is increased in CRC tissues. Elevated level of LINC00265 is correlated with lymph node metastases and advanced pathological stage. We obtained 269 LINC00265 related genes; the results of functional analysis of these genes revealed that LINC00265 might involve in carcinogenesis of CRC. In addition, further experiments indicated that LINC00265 knockdown impaired cell proliferation and invasion, promoted cell cycle distribution and apoptosis in HT29 cells. Moreover, Western blot analysis revealed that downregulation of LINC00265 suppressed the expression of EGFR. CONCLUSION: Our results indicate that LINC00265 induces cell proliferation, migration and inhibits CRC cells apoptosis by targeting EGFR. LINC00265 could be served as a diagnostic factor and therapeutic target for CRC patients.

The Long Non-Coding RNA SBF2-AS1 Exerts Oncogenic Functions In Gastric Cancer By Targeting The miR-302b-3p/E2F Transcription Factor 3 Axis.

BACKGROUND AND AIMS: Studies show that the long non-coding RNA, SBF2-AS1, plays a critical role in cancer progression, but the role of SBF2-AS1 in gastric cancer has not been reported. Therefore, this study aimed to elucidate the mechanism of SBF2-AS1 in gastric cancer (GC). METHODS: A meta-analysis, based on the gene expression omnibus database and TCGA dataset was performed to explore the prognostic value of SBF2-AS1 in GC. RT-PCR was also conducted to investigate the clinicopathologic value of SBF2-AS1 in GC. The effect of SBF2-AS1 in GC cell lines was conducted by gain or loss-of-function assays, and the SBF2-AS1 target gene was confirmed using a luciferase reporter assay and bioinformatics. RESULTS: SBF2-AS1 was overexpressed in GC tissues and cell lines, and SBF2-AS1 overexpression indicated poor overall survival and could serve as an independent prognostic factor. Moreover, knockdown of SBF2-AS1 inhibited cell growth, invasion, and metastasis, promoted apoptosis, and caused cell cycle arrest. Luciferase reporter and gain- or loss-of-function assays indicated that SBF2-AS1 acted as a competing endogenous (ceRNA) for microRNA (miR)-302b-3p, which blocked the inhibitory effect of miR-302b-3p on the E2F transcription factor 3 (E2F3). CONCLUSION: SBF2-AS1 could be a potential diagnostic and prognostic biomarker in GC, and SBF2-AS1 accelerates tumor progression via the miR-302b-3p/E2F3 axis.

Long Non-coding RNA ITIH4-AS1 Accelerates the Proliferation and Metastasis of Colorectal Cancer by Activating JAK/STAT3 Signaling.

Accumulating evidence has uncovered long non-coding RNAs (lncRNAs) as central regulators in the pathogenesis of diverse human cancers including colorectal cancer (CRC). The present study discovered that a novel lncRNA ITIH4 antisense RNA 1 (ITHI4-AS1) was frequently under-expressed in most normal human tissues, including colon tissues. Therefore, we aimed to investigate the role of ITHI4-AS1 in CRC. Interestingly, a significant overexpression of ITIH4-AS1 was observed in CRC cell lines relative to normal NCM460 cells. Also, we investigated the facilitating role of ITIH4-AS1 in CRC cell growth and metastasis both in vitro and in vivo. Additionally, we explained that ITIH4-AS1 upregulation in CRC was attributed to downregulation or even depletion of RE1 silencing transcription factor (REST), a presently identified transcriptional repressor for ITIH4-AS1. Meanwhile, the contribution of ITIH4-AS1 to CRC development was validated to rely on the activation of the JAK/STAT3 pathway. More importantly, we verified that FUS interacted with both ITIH4-AS1 and STAT3, and that ITIH4-AS1 evoked nuclear translocation of phosphorylated (p)-STAT3 in CRC through recruiting FUS. In summary, our findings unveiled for the first time that REST downregulation-enhanced ITIH4-AS1 exerts pro-tumor functions in CRC through FUS-dependent activation of the JAK/STAT3 pathway, implying that targeting ITIH4-AS1 may be a novel effective strategy for CRC therapy.

SUCO as a Promising Diagnostic Biomarker of Hepatocellular Carcinoma: Integrated Analysis and Experimental Validation.

BACKGROUND Hepatocellular carcinoma (HCC) is not frequently diagnosed until the late stage due to its concealed symptoms. Therefore, the identification of biomarkers that have effective diagnostic performance and act as potential key therapeutic targets for HCC becomes urgent. MATERIAL AND METHODS Comprehensive analysis of accumulated data downloaded from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases was used to obtain more reliable potential diagnostic biomarkers of HCC and to explore related molecular mechanisms. Meta-analysis and summary receiver operating characteristic (SROC) curve analysis were performed to evaluate the differential expression of SUCO gene in HCC and identify the capability of SUCO in distinguishing HCC-tissues from normal liver-tissues. RESULTS SUCO was found to be upregulated in HCC-tissues and exhibited a favorable value in diagnosing HCC. Bioinformatics analysis showed that SUCO might play important roles in HCC progression, and was significantly related to cell cycle, cell metabolism, and proliferation. CONCLUSIONS This study was the first to demonstrate that SUCO was overexpressed in HCC-tissues, and that high expression of SUCO was significantly related to poor overall survival in HCC patients. SUCO might be a potential diagnostic biomarker for HCC patients, which promotes the tumorigenesis and progression of HCC.

The prognostic value of LINC01296 in pan-cancers and the molecular regulatory mechanism in hepatocellular carcinoma: a comprehensive study based on data mining, bioinformatics, and in vitro validation.

BACKGROUND AND AIMS: This study aimed to clarify the prognostic role of LINC01296 in various cancers, and to evaluate its effect on proliferation, metastasis, and the cell cycle in hepatocellular carcinoma (HCC) by data mining, bioinformatics, and in vitro validation. METHODS: The prognostic role of LINC01296 in cancer patients was assessed by searching the PubMed, Embase, Web of Science, and Gene Expression Omnibus databases and calculating pooled hazard ratios (HRs) with 95% confidence intervals (CIs); this prognostic role was also evaluated using The Cancer Genome Atlas (TCGA). We detected LINC01296 expression in HCC cell lines, and lentivirus-mediated small interfering RNAs were used to silence LINC01296 in MHCC97H and Hep3B cells to explore the role of LINC01296 in cell proliferation, metastasis, and cell cycle progression with in vitro validation and bioinformatics. RESULTS: The results indicated that LINC01296 overexpression was associated with poor overall survival (OS) and disease-free survival (DFS) in various cancers; however, LINC01296 expression was not associated with recurrence-free survival (RFS). Similar results were found with TCGA, which showed that LINC01296 expression was associated with the pathologic stage, tumor size, and differentiation in Asian cancer patients. Additionally, bioinformatics analysis revealed expression of 394 related genes, which indicated that LINC01296 could be involved in the tumorigenesis and progression of HCC. In vitro gene silencing experiments indicated that LINC01296 downregulation repressed cell proliferation, cell cycle progression, and the metastatic potential of HCC through the regulation of BUB1, CCNA2, and CDK1 expression. CONCLUSION: This study demonstrated that LINC01296 expression is related to poor OS and DFS in a variety of cancer types and that LINC01296 has an oncogenic role in HCC.

Pseudogene DUXAP10 acts as a diagnostic and prognostic marker and promotes cell proliferation by activating PI3K/AKT pathway in hepatocellular carcinoma.

Background: Recently, the pseudogene DUXAP10 was shown to be overexpressed in various human cancers and emerged as a key cancer regulator. However, the roles of DUXAP10 in hepatocellular carcinoma (HCC) tumorigenesis and progression remain uncharacterized. Methods: Comprehensive analyses were performed to investigate DUXAP10 expression patterns, potential biologic functions, and clinical significance in HCC based on the data downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. DUXAP10 expression levels in HCC tissue sections and cells were verified using quantitative real-time PCR analysis. DUXAP10-siRNA was used to silence DUXAP10 in the Hep3B cell line to determine the roles of DUXAP10 in HCC cell proliferation. Results: DUXAP10 was significantly overexpressed in HCC, and DUXAP10 upregulation was closely associated with poor prognoses in HCC patients. DUXAP10 knockdown decreased cell proliferation and arrested HCC cells in the G1 phase of the cell cycle. Western blot analysis showed that DUXAP10 knockdown decreased p-AKT expression in HCC cells. Conclusion: Our study demonstrates that pseudogene DUXAP10 promotes HCC cell proliferation by activating PI3K/AKT pathway and could act as a potential diagnostic and prognostic biomarker for HCC patients.

Comprehensive analysis of potential prognostic genes for the construction of a competing endogenous RNA regulatory network in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an extremely common malignant tumor with worldwide prevalence. The aim of this study was to identify potential prognostic genes and construct a competing endogenous RNA (ceRNA) regulatory network to explore the mechanisms underlying the development of HCC. METHODS: Integrated analysis was used to identify potential prognostic genes in HCC with R software based on the GSE14520, GSE17548, GSE19665, GSE29721, GSE60502, and the Cancer Genome Atlas databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway-enrichment analyses were performed to explore the molecular mechanisms of potential prognostic genes. Differentially expressed miRNAs (DEMs) and lncRNAs (DELs) were screened based on the Cancer Genome Atlas database. An lncRNA-miRNA-mRNA ceRNA regulatory network was constructed based on information about interactions derived from the miRcode, TargetScan, miRTarBase, and miRDB databases. RESULTS: A total of 152 potential prognostic genes were screened that were differentially expressed in HCC tissue and significantly associated with overall survival of HCC patients. There were 13 key potential prognostic genes in the ceRNA regulatory network: eleven upregulated genes (CCNB1, CEP55, CHEK1, EZH2, KPNA2, LRRC1, PBK, RRM2, SLC7A11, SUCO, and ZWINT) and two downregulated genes (ACSL1 and CDC37L1) whose expression might be regulated by eight DEMs and 61 DELs. Kaplan-Meier curve analysis showed that nine DELs (AL163952.1, AL359878.1, AP002478.1, C2orf48, C10orf91, CLLU1, CLRN1-AS1, ERVMER61-1, and WARS2-IT1) in the ceRNA regulatory network were significantly associated with HCC-patient prognoses. CONCLUSION: This study identified potential prognostic genes and constructed an lncRNA- miRNA-mRNA ceRNA regulatory network of HCC, which not only has important clinical significance for early diagnoses but also provides effective targets for HCC treatments and could provide new insights for HCC-interventional strategies.

DUXAP8 a Pan-Cancer Prognostic Marker Involved in the Molecular Regulatory Mechanism in Hepatocellular Carcinoma: A Comprehensive Study Based on Data Mining, Bioinformatics, and in vitro Validation.

BACKGROUND: Double homeobox A pseudogene 8 (DUXAP8) has been identified as a key regulator at the posttranscriptional level in various types of cancers. However, whether DUXAP8 has a role in hepatocellular carcinoma (HCC) progression remains to be determined. Here, we aimed to investigate the potential clinical value of DUXAP8 as a pan-cancer marker, and its role in HCC development through an integrated analysis strategy and in vitro experimental validation. METHODS: Comprehensive analysis was performed using data mined from public databases to evaluate the expression patterns and clinical value of DUXAP8 in human pan-cancers. Bioinformatics analysis was performed to investigate the potential biological functions of DUXAP8 in HCC based on TCGA database. Real-time qPCR analysis was used to examine the expression levels of DUXAP8 in HCC tissue samples and cell lines. DUXAP8-siRNA was used to silence DUXAP8 in the Hep-G2 cell line to examine the role of DUXAP8 in HCC cell proliferation and invasion. RESULTS: DUXAP8 was significantly upregulated in various types of human cancers and could serve as a potential pan-cancer diagnostic and prognostic biomarker. Bioinformatics analysis suggested that DUXAP8 might be involved in the regulation of the biological processes of HCC cell cycle, cell division and cell proliferation. Additionally, downregulation of DUXAP8 inhibited HCC cell proliferation and invasion in vitro. CONCLUSION: This study revealed that DUXAP8 may serve as a potential pan-cancer prognostic and diagnostic marker in humans. In addition, DUXAP8 promoted HCC cell proliferation and invasion, suggesting that it may represent a novel therapeutic target for HCC.

XB130 Knockdown Inhibits the Proliferation, Invasiveness, and Metastasis of Hepatocellular Carcinoma Cells and Sensitizes them to TRAIL-Induced Apoptosis.

BACKGROUND: XB130 is a recently discovered adaptor protein that is highly expressed in many malignant tumors, but few studies have investigated its role in hepatocellular carcinoma (HCC). Therefore, this study explored the relationship between this protein and liver cancer and investigated its molecular mechanism of action. METHODS: The expression of XB130 between HCC tissues and adjacent nontumor tissues was compared by real-time polymerase chain reaction, immunochemistry, and Western blotting. XB130 silencing was performed using small hairpin RNA. The effect of silencing XB130 was examined using Cell Counting Kit-8, colony assay, wound healing assay, and cell cycle analysis. RESULTS: We found that XB130 was highly expressed in HCC tissues (cancer tissues vs. adjacent tissues: 0.23 ± 0.02 vs. 0.17 ± 0.02, P < 0.05) and liver cancer cell lines, particularly MHCC97H and HepG2 (MHCC97H and HepG2 vs. normal liver cell line LO-2: 2.35 ± 0.26 and 2.04 ± 0.04 vs. 1.00 ± 0.04, respectively, all P < 0.05). The Cell Counting Kit-8 assay, colony formation assay, and xenograft model in nude mice showed that silencing XB130 inhibited cell proliferative ability both in vivo and in vitro, with flow cytometry demonstrating that the cells were arrested in the G0/G1 phase in HepG2 (HepG2 XB130-silenced group [shA] vs. HepG2 scramble group [NA]: 74.32 ± 5.86% vs. 60.21 ± 3.07%, P < 0.05) and that the number of G2/M phase cells was decreased (HepG2 shA vs. HepG2 NA: 8.06 ± 2.41% vs. 18.36 ± 4.42%, P < 0.05). Furthermore, the cell invasion and migration abilities were impaired, and the levels of the epithelial-mesenchymal transition-related indicators vimentin and N-cadherin were decreased, although the level of E-cadherin was increased after silencing XB130. Western blotting showed that the levels of phosphorylated phosphoinositide 3-kinase (PI3K) and phospho-protein kinase B (p-Akt) also increased, although the level of phosphorylated phosphatase and tensin homolog increased, indicating that XB130 activated the PI3K/Akt pathway. Furthermore, we found that a reduction in XB130 increased liver cancer cell sensitivity to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. CONCLUSIONS: Our findings suggest that XB130 might be used as a predictor of liver cancer as well as one of the targets for its treatment.

Long non-coding RNA CASC2 in solid tumors: A meta-analysis.

BACKGROUND AND AIM: Recently, several studies have reported that the long non-coding RNA cancer susceptibility 2 (CASC2) is downregulated in human solid tumors. However, as the sample size in those studies was limited, the role of CASC2 in cancer remains unknown. Accordingly, we conducted this meta-analysis to explore the role of CASC2 in solid tumors. METHODS: We systematically searched the PubMed, Medline, Cochrane Library, Web of Science, EMBASE, Ovid, Chinese CNKI, and Chinese WanFang databases. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence interval (CI) were used to evaluate the relation between CASC2 and the clinicopathological characteristics and prognosis of patients with cancer. Additionally, we also use The Cancer Genome Atlas (TCGA) dataset to analyze CASC2 expression. RESULTS: A total of 15 studies with 1158 patients were included in this meta-analysis. The pooled results demonstrated that the expression of CASC2 was related to tumor size (large vs. small: OR = 0.40, 95% CI = [0.30, 0.52]), differentiation (low vs. high+ moderate: OR = 0.42, 95% CI = [0.29, 0.62]) and TNM stage (I + II vs. III + IV: OR = 2.74, 95% CI = [2.08, 3.60]), but not to age, gender and differentiation. High CASC2 expression indicated better overall survival (OS) (HR = 0.41, 95% CI = [0.32, 0.50]) and disease-free survival (DFS) (HR = 0.48, 95% CI = [0.26, 0.66]). Additionally, similar results were obtained through analysis of the TCGA data set. Moreover, it was determined that CASC2 could be an independent predictive factor for OS (HR = 0.38, 95% CI = [0.22, 0.54]) in patients with cancer. CONCLUSION: This analysis revealed that low CASC2 expression was correlated with advanced clinicopathological characteristics of cancer tumors, and CASC2 may thus be a potential prognostic biomarker in human cancer. However, more studies are needed to further corroborate these findings.

DcR3 induces proliferation, migration, invasion, and EMT in gastric cancer cells via the PI3K/AKT/GSK-3ß/ß-catenin signaling pathway.

BACKGROUND: Decoy receptor 3 (DcR3) has been reported to be overexpressed in a wide variety of malignancies and is correlated with tumorigenesis and progression. In gastric cancer (GC), DcR3 overexpression is associated with lymph node and distant metastasis, as well as poor prognosis. However, the functional role of DcR3 expression in GC remains elusive. PURPOSE: The aim of this study is to elucidate the direct role of DcR3 in regulating GC progression and metastasis and identify the potential mechanism. METHODS: DcR3 expression was stably knocked down in HGC27 and MKN28 cells by transfecting the cells with DcR3 shRNA using lentiviral vector system. After the knockdown of DcR3 was confirmed, cell proliferation, colony formation, cell cycle distribution, apoptosis, cell invasion and migration were assessed in vitro. In addition, Western blot analysis was performed to evaluate the expression of downstream mediators of DcR3. Comparisons between multiple groups were performed using one-way analysis of variance (ANOVA) or unpaired Student's t-test. Differences were considered significant at P<0.05. RESULTS: Our findings demonstrate that DcR3 induces proliferation, migration, invasion, and promotes epithelial-mesenchymal transition (EMT) of GC cells. In addition, DcR3 increases the expression levels of several components of the PI3K/AKT/GSK-3ß/ß-catenin signaling pathway, such as p-AKT, GSK-3ß, p-GSK-3ß and ß-catenin. Additionally, DcR3 also enhances the expression of N-cadherin and Vimentin and decreases the expression of E-cadherin. CONCLUSION: In summary, the findings of this study indicate that during GC progression, DcR3 plays a key role in cell proliferation and invasion via the PI3K/AKT/GSK-3ß/ß-catenin signaling pathway. Thus, targeting DcR3 might be a potential therapeutic approach for the treatment of GC.

Clinicopathological and prognostic significance of FoxM1 in hepatocellular carcinoma patients: a meta-analysis.

BACKGROUND AND AIMS: Recently, the abnormal expression of FoxM1 has been found in many malignant tumors. However, the clinicopathological and prognostic value of FoxM1 expression in hepatocellular carcinoma (HCC) patients remains controversial. We conducted a meta-analysis to establish the relationship between FoxM1 expression and the clinicopathological features and prognostic value in patients with HCC. METHODS: An electronic search for relevant articles was conducted according to a set of criteria in the PubMed, Cochrane Library, Web of Science, EMBASE, Chinese CNKI and Chinese WanFang databases. The correlation data between FoxM1 expression and clinicopathological features and survival outcomes were analyzed. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were calculated using STATA14.2. RESULTS: A total of 14 studies comprising of 2,036 patients were enrolled in this meta-analysis. The results showed that FoxM1 expression was related to the incidence, tumor size (>5 cm), vascular invasion, differentiation and TNM stage. Moreover, overexpression of FoxM1 indicated a poor 3- and 5-year overall survival rate (OS) and recurrence-free survival rate (disease-free survival rate). CONCLUSION: Our meta-analysis indicated that FoxM1 expression was associated with incidence, tumor size (>5 cm), vascular invasion, differentiation and TNM stage. Accordingly, FoxM1 may be a reliable prognostic biomarker for patients with HCC. However, additional high-quality studies are still needed to further support these findings.

The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells.

Dysfunctional Fas ligand (FasL) may inhibit the apoptosis of tumor cells. FasL contains two receptors, Fas and Decoy Receptor 3 (DcR3). DcR3 competitively binds to FasL over Fas, resulting in the inhibition of FasL-mediated apoptosis. Therefore, it was suggested that the downregulation of DcR3 expression enhances FasL-mediated apoptosis. In the current study, the expression of DcR3 was silenced in liver cancer HepG2 cells in order to study the effect of FasL on HepG2 cell activity and invasiveness. DcR3 siRNA knockdown HepG2 cells (KD), DcR3 blank plasmid control HepG2 cells and wild-type HepG2 cells (WT) were treated with FasL (10 ng/ml). Flow cytometry was used to detect changes in the cell cycle and apoptosis. MTS, clonogenic, wound healing and Transwell assays were performed to examine changes in cell activity, proliferation, migration and invasiveness. Reverse transcription polymerase chain reaction and western blot analysis were performed to measure the expression of DcR3, matrix metallopeptidase 9 (MMP9), vascular endothelial growth factor (VEGF)-C and VEGF-D. The results demonstrated that, compared with WT cells, the proportion of KD cells in the G2/M phase decreased following treatment with FasL. KD cells were more sensitive to FasL-induced apoptosis. Following treatment with FasL, the activity and proliferation, migration and invasion of KD cells were reduced, and the expression of MMP9, VEGF-C and VEGF-D decreased. Furthermore, it was demonstrated that DcR3 is involved in the proliferation and invasion of HepG2 cells, and this mechanism may be associated with the regulatory effect of the expression of MMP9, VEGF-C and VEGF-D; however, the exact mechanism of action remains unclear. FollowingDcR3 silencing, FasL-mediated apoptosis increased in HepG2 cells. Therefore, DcR3 combined with FasL may be a potential target for the treatment of liver cancer.

Role of Beclin1 expression in patients with hepatocellular carcinoma: a meta-analysis.

BACKGROUND AND AIM: Beclin1 has been reported as a vital marker for a number of malignant tumors. However, the role of Beclin1 in hepatocellular carcinoma (HCC) remains inconclusive. Thus, we conducted a meta-analysis to assess the correlation between Beclin1 and its clinicopathological and prognostic values in HCC. METHODS: PubMed, Cochrane Library, Web of Science, EMBASE, Chinese CNKI, and Chinese WanFang databases were searched for published articles on Beclin1 expression in hepatocellular tissues. Standard-compliant articles were screened using the Newcastle-Ottawa Scale for strict quality control of the literature. The correlation of Beclin1 expression with the clinicopathological features and survival outcomes was analyzed. Pooled odds ratios and hazard ratios with 95% confidence intervals were calculated using STATA14.2. RESULTS: Eleven articles with 1,279 patients were included in this meta-analysis. Positive Beclin1 expression was found to be correlated with alpha fetoprotein, liver cirrhosis, and vascular invasion, but not with gender, age, HBsAg, size of tumor, number of tumors, differentiation, and TNM stage. Positive Beclin1 expression was also associated with favorable 5-year overall survival and disease-free survival rates. CONCLUSION: Our meta-analysis indicated that positive Beclin1 expression was negatively related to alpha fetoprotein, liver cirrhosis, and vascular invasion in HCC. Beclin1 could be used as a prognostic biomarker for HCC.

The clinicopathological and prognostic value of long non-coding RNA ZEB1-AS1 in solid tumors: A meta-analysis.

BACKGROUND AND AIM: Studies have reported that Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) is overexpressed in many malignant tumors. However, the sample size in those studies was limited, so the clinicopathological and prognostic value of ZEB1-AS1 in solid tumors remains undetermined, Accordingly, the aim of this meta-analysis was to evaluate the relationship between the expression of lncRNA ZEB1-AS1 and clinicopathological characteristics and prognosis in patients with solid tumors. METHODS: Pooled odds ratios (ORs) and hazard ratios (HRs) were estimated with 95% confidence interval (CI) to assess the relation between ZEB1-AS1 and the clinicopathological characteristics and prognosis of patients with cancer. RESULTS: A total of 10 studies, comprising 861 patients, were included in this meta-analysis. The pooled results suggested that high ZEB1-AS1 expression was related to low differentiation (low vs. high + moderate: OR = 2.99, 95% CI = [2.03, 4.39]), increased lymph node metastasis (YES vs. NO: OR = 4.62, 95% CI = [2.90, 7.37]) and advanced TNM stage (I + II vs. III + IV: OR = 0.41, 95% CI = [0.23, 0.75]), but not to gender and tumor size. Moreover, high ZEB1-AS1 expression was associated with poor overall survival (OS; HR = 1.86, 95% CI = [1.57, 2.14]) and disease-free survival (DFS; HR = 2.03, 95% CI = [1.28, 2.77]). Thus, ZEB1-AS1 could be an independent predictive factor for OS (HR = 2.07, 95% CI = [1.57, 2.56]) in patients with cancers. CONCLUSION: High expression of ZEB1-AS1 was associated with advanced clinicopathological characteristics, and ZEB1-AS1overexpression may be a potential prognostic biomarker in human cancer. However, more studies involving various tumor types and large sample size are needed.