The prognostic value of YAP1 on clinical outcomes in human cancers.
Ontology highlight
ABSTRACT:
SUBMITTER: Wu Y
PROVIDER: S-EPMC6814621 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
The prognostic value of YAP1 on clinical outcomes in human cancers.
Wu Ying Y Hou Yanshen Y Xu Peng P Deng Yujiao Y Liu Kang K Wang Meng M Tian Tian T Dai Cong C Li Na N Hao Qian Q Song Dingli D Zhou Ling Hui LH Dai Zhijun Z
Aging 20191015 19
<h4>Background</h4>As an important downstream factor in the Hippo pathway, yes-associated protein 1(YAP1) has been detected to be elevated in various cancers and demonstrated to play a role in tumor development. Therefore, we evaluated by a meta-analysis the prognostic value of YAP1 in cancer patients.<h4>Results</h4>Sixty-eight studies with 8631 patients were identified. The results indicated that YAP1 overexpression predicted unfavorable patient prognosis in studies with overall survival (OS) ...[more]
Similar Datasets
Project description:Background: This updated meta-analysis aimed to analyze available data to explore the prognostic value of long noncoding RNA breast cancer anti-estrogen resistance 4 (BCAR4) in various human malignancies. Methods: Literature retrieval was performed by systematic searching several authoritative databases, including Pubmed, PMC database, Web of Science, the Cochrane Library, Embase, and CNKI database up to Feb 10, 2019. Data were extracted and subsequently crosschecked, and discrepancies were discussed to reach consensus. Quality of the eligible studies was evaluated by Newcastle-Ottawa Scale (NOS). The fixed- or random-effects model was used to calculate the pooled the hazard ratios (HRs) or odds ratios (ORs) and the 95% confidence interval (95% CI). Publication bias was detected by using Begg's funnel plot and Egger's test. Results: A total 1,128 cancer patients from thirteen studies were included and pooled in the present meta-analysis. High expression levels of BCAR4 were correlated with unfavorable overall survival (OS) (HR=2.23, 95% CI: 1.84-2.71), but not progression-free survival (PFS) (HR=1.30, 95% CI: 0.80-2.11). Subgroup stratified analysis showed that tumor type, sample size, follow-up months, and survival analysis method did not alter the predictive value of BCAR4 on OS in various cancers. Furthermore, elevated BCAR4 level was markedly correlated with advanced clinical stage (III/IV) (OR=3.28, 95% CI: 2.33-4.60), and dramatically predicted lymph node metastasis (OR=3.00, 95% CI: 1.95-4.63, P<0.00001) and distant metastasis (OR=3.36, 95% CI: 1.88-5.98, P<0.0001), but not associated with age, gender or tumor size. No obvious heterogeneity was noted for correlation between BCAR4 expression and OS across these studies. Conclusions: High expression of BCAR4 was correlated with unfavorable overall survival outcome and clinical features including metastasis and progression, implicating an independent prognostic value for BCAR4 in human cancers.
| S-EPMC6856575 | biostudies-literature
Project description:BackgroundYes-associated protein 1 (YAP1) is an effector of Hippo pathway, which is critical for regulating organ size, cell proliferation and tumor growth in mammals. Many previous studies have explored the relationship between YAP1 and various types of cancer. However, these studies were limited by the small samples size and the findings were inconsistent among them. Therefore, a meta-analysis was conducted to assess the association between YAP1 and malignancies.MethodsA systematic literature search was conducted for eligible studies in the PubMed, Corchane Library, Web of Knowledge, EMBASE and CBM disc databases from inception to August 1st 2014. After heterogeneity analysis, pooled harzad ratio (HR) with 95% confidence interval (95%CI) using both fixed and random effect models were estimated in STATA 10.0. Meta regression analysis, subgroup analysis and sensitivity analysis were performed to explore the potential sources of heterogeneity and to evaluate the robustness of the result. Publication bias was assessed by Egger's test and funnel plot.ResultsA total of 21 unique articles from 2009 to 2014, comprising 2983 patients, were analyzed in the meta-analysis. The association of YAP1 expression and overall survival time (OS) was evaluated in 20 studies including 2067 patients. Positive YAP1 showed poorer OS (HR = 1.826; 95% CI = 1.465-2.275; p <0.002). For evaluating disease-free survival time (DFS), 10 studies with 1139 patients were analyzed. Positive YAP1 indicated worse DFS (HR = 2.114; 95%CI = 1.406-3.179; p <0.001). Subgroup analysis showed that both positive nuclear YAP1 (HR = 1.390, 95% CI: 0.810-2.400, p = 0.729) and up-regulation overall YAP1 (HR = 2.237, 95% CI: 1.548-3.232, p <0.001) had poorer OS for patients with malignancies. Similarly, both positive nuclear YAP1 (HR = 3.733, 95% CI: 1.469-9.483, p = 0.001) and up-regulation overall YAP1 (HR = 1.481, 95% CI: 1.163-1.886, p = 0.554) showed worse DFS. The patients with urogenital system cancer had the poorest OS (HR = 2.133, 95% CI: 1.549-2.937, p = 0.020). The patients with alimentary system cancer had the most significant impact on DFS (HR = 1.879, 95% CI: 1.537-2.297, p <0.001).ConclusionBoth overall and nuclear YAP1 overexpression are intimately associated with adverse OS and DFS in numerous cancers, suggesting that YAP1 may act as a potential therapeutic targets of these malignancies in the future.
| S-EPMC4532485 | biostudies-literature
Project description:Background: Yes-associated protein 1 (YAP1) is the main downstream effector of the Hippo signaling pathway, which is involved in tumorigenesis. This study aimed to comprehensively understand the prognostic performances of YAP1 expression and its potential mechanism in pan-cancers by mining databases. Methods: The YAP1 expression was evaluated by the Oncomine database and GEPIA tool. The clinical significance of YAP1 expression was analyzed by the UALCAN, GEPIA, and DriverDBv3 database. Then, the co-expressed genes with YAP1 were screened by the LinkedOmics, and annotated by the Metascape and DAVID database. Additionally, by the MitoMiner 4.0 v tool, the YAP1 co-expressed genes were screened to obtain the YAP1-associated mitochondrial genes that were further enriched by DAVID and analyzed by MCODE for the hub genes. Results: YAP1 was differentially expressed in human cancers. Higher YAP1 expression was significantly associated with poorer overall survival and disease-free survival in adrenocortical carcinoma (ACC), brain Lower Grade Glioma (LGG), and pancreatic adenocarcinoma (PAAD). The LinkedOmics analysis revealed 923 co-expressed genes with YAP1 in adrenocortical carcinoma, LGG and PAAD. The 923 genes mainly participated in mitochondrial functions including mitochondrial gene expression and mitochondrial respiratory chain complex I assembly. Of the 923 genes, 112 mitochondrial genes were identified by MitoMiner 4.0 v and significantly enriched in oxidative phosphorylation. The MCODE analysis identified three hub genes including CHCHD1, IDH3G and NDUFAF5. Conclusion: Our findings showed that the YAP1 overexpression could be a biomarker for poor prognosis in ACC, LGG and PAAD. Specifically, the YAP1 co-expression genes were mainly involved in the regulation of mitochondrial function especially in oxidative phosphorylation. Thus, our findings provided evidence of the carcinogenesis of YAP1 in human cancers and new insights into the mechanisms underlying the role of YAP1 in mitochondrial dysregulation.
| S-EPMC8262238 | biostudies-literature
Project description:CSNK1D, also known as CK1δ, is a crucial gene involved in various biological processes such as cell cycle, transcriptional regulation, apoptosis, cell polarity, and cell motility. It is associated with different cancers and neurodegenerative diseases. This study aimed to investigate the role of CSNK1D in multiple human cancers, particularly hepatocellular carcinoma (HCC), through in vitro experiments. The research utilized various online resources and databases like UCSC, NCBI, GEPIA2, HPA, cBioPortal, SangerBox, UALCAN, and TCGA for analyzing CSNK1D expression, prognosis significance, immune features, and gene alterations in cancers. RT-PCR was employed to evaluate CSNK1D expression in normal liver and liver cancer cell lines. In vitro experiments, including CCK-8, Edu, wound healing, and Transwell assays, were conducted to assess CSNK1D's biological function in HCC cells. Results demonstrated consistent upregulation of CSNK1D in various tumors. Heightened CSNK1D expression correlated with reduced overall survival and disease-free survival rates in different cancer patient cohorts. Significant associations were found between CSNK1D expression levels and immune cell infiltrations, immune checkpoint inhibitors, tumor mutation burden, and microsatellite instability across multiple malignancies. Notably, statistical analyses using TCGA and ICGC data identified CSNK1D as a robust and independent prognostic biomarker in HCC. Inhibiting CSNK1D expression effectively hindered cell proliferation, migration, and invasion in cellular experiments. In conclusion, this study suggests that CSNK1D may serve as a biomarker for tumor prognosis and immunotherapy. It influences the proliferation and metastasis of HCC cells.
| S-EPMC10522368 | biostudies-literature
Project description:BackgroundMCM3AP antisense RNA 1 (MCM3AP-AS1) is a newly identified potential tumor biomarker. Nevertheless, the prognostic value of MCM3AP-AS1 in cancer has been inconsistent in the available studies. We performed this meta-analysis to identify the prognostic role of MCM3AP-AS1 in various cancers.MethodsWe searched PubMed, Web of Science, EMBASE, and the Cochrane Library databases to screen relevant studies. Hazard ratios (HR) or odds ratios (OR) and corresponding 95% confidence intervals (CI) were used to evaluate the relationship between aberrant MCM3AP-AS1 expression and survival and clinicopathological features (CFS) of cancer patients. A meta-analysis was performed using STATA 12.0 software. Additionally, results were validated by an online database based on The Cancer Genome Atlas (TCGA). Subsequently, we analyzed the MCM3AP-AS1-related genes and molecular mechanisms based on the MEM database.ResultsOur results showed that overexpression of MCM3AP-AS1 was related to poor overall survival (OS) (HR = 2.00, 95% CI, 1.52-2.64, P < 0.001) and relapse-free survival (RFS) (HR = 3.28, 95% CI 1.56-6.88, P = 0.002). In addition, MCM3AP-AS1 overexpression was associated with TNM stage, differentiation grade, and lymph node metastasis, but not significantly with age, gender, and tumor size. In addition, MCM3AP-AS1 overexpression was verified by the GEPIA online database to be associated with poorer survival. The further functional investigation suggested that MCM3AP-AS1 may be involved in several cancer-related pathways.ConclusionsThe overexpression of MCM3AP-AS1 was related to poor survival and CFS. MCM3AP-AS1 may be considered a novel prognostic marker and therapeutic target in various cancers.
| S-EPMC9249515 | biostudies-literature
Project description:BackgroundThe Dickkopf1 (DKK1) gene encodes a protein that belongs to the Dickkopf family. The protein can inhibit the Wnt signaling pathway which plays a key role in the carcinogenesis and progression of various types of cancers. Based on this, we hypothesized that the differential expression of DKK1 may figure significantly in cancers by regulating Wnt signaling pathway transduction. In this study, we conducted bioinformatics analysis to evaluate the prognostic and therapeutic value of DKK1 expression level in human cancers.MethodsThe expression level was analyzed by using the Oncomine database and Gene Expression Profiling Interactive Analysis tool. The analysis of prognosis was conducted by using the UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA), and DriverDBv3 databases. We also investigated using DKK1 promoter methylation to define cancer types through the UALCAN database. Meanwhile, the related functional networks of DKK1 were analyzed by using the GeneMANIA interactive tool and Cytoscape software. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted using the Metascape online website, and we used the cBioPotartal database to explored DKK1 expression, aberrant information, and the co-expression genes in the subgroups of lung cancer. Finally, we performed the overall survival (OS) meta-analysis of the DKK1 expression in lung squamous cell carcinoma (LUSC) via the Lung Cancer Explorer (LCE).ResultsDKK1 was differentially expressed in different types of human cancers. DKK1 was overexpressed in human cancers including head and neck squamous cell carcinoma (HNSC), LUSC, and pancreatic adenocarcinoma (PAAD). Overexpression of DKK1 indicated adverse OS in bladder urothelial carcinoma (BLCA), HNSC, and PADD, but no difference in OS was found between the LUSC and healthy groups. The high expression of DKK1 was also associated with shorter disease-free survival (DFS) in HNSC, LUSC, and PAAD. Gene regulation network analysis indicated that DKK1 was mainly involved in Wnt signaling pathways and several other signaling pathways.ConclusionsOur findings showed that DKK1 is significantly expressed in various cancers and could be a biomarker for targeted therapy and a predictor for prognosis of these specific cancers. The bioinformatics analysis revealed a significant overexpression of DKK1 in HNSC, LUSC, and PAAD, with DKK1 overexpression being associated with adverse outcome in these patients, but how DKK1 expression levels relate to hematological malignancies and prognosis is still unclear. These new insights into the function of DKK1 may provide a basis for new targeted drug therapy and an avenue for further investigation into the mechanisms underlying carcinogenesis of DKK1 in different cancer types.
| S-EPMC7214893 | biostudies-literature
Project description:MORF4-related gene-binding protein (MRGBP) is the subunit of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. Much of the research indicated an oncogenic role of MRGBP in the development of cancers. However, it is still unknown the role MRGBP plays in human cancers, which deserves further exploration. In this research, the expression profile, prognostic value of MRGBP, and the relationship between MRGBP and immune infiltration were explored in 33 types of cancer. The differences in MRGBP expression in tumor and normal tissues were explored using data from The Cancer Genome Atlas, Gene Expression Omnibus and ONCOMINE. Analysis of the association between MRGBP and prognosis using Kaplan-Meier survival curve and COX analysis. The data of Tumor mutational burden (TMB), microsatellite instability (MSI) from TCGA. The relationship Between MRGBP expression and immunity was analyzed using the ESTIMATE algorithm and CIBERSORT. Furthermore, we explored MRGBP expression and the relationship between MRGBP expression and macrophage infiltration using immunohistochemical analysis in lower grade glioma (LGG). Our results revealed that MRGBP was highly expressed in most cancer tissues compared with normal tissues. Tumors with increased MRGBP expression had a high clinicopathologic stage and poor prognosis. The expression of MRGBP was closely related to the TMB, MSI. We also found a significant negative correlation between MRGBP expression and stromal scores and immune scores in various types of cancer. Furthermore, MRGBP expression was associated with a variety of immune cells including B cells, NK cells, T cells, and macrophages. LGG and LIHC was selected as representative cancer types for further study, the results of immunohistochemistry indicated that the protein levels of MRGBP were significantly elevated in tumor tissues. Moreover, our LIHC data analysis showed that patients with high MRGBP expression were associated with short survival rates and MRGBP was a risk factor to determine OS. Immunohistochemistry also confirmed that M0 macrophage infiltration in the MRGBP-high group significantly increased. In conclusion, these results reveal that MRGBP can serve as a potential prognostic biomarker and it plays an important role in tumor immune infiltration in various tumors, especially in LGG and LIHC.
| S-EPMC8511499 | biostudies-literature
Project description:Recent evidence indicates that miR-17-92 family might be an essential prognostic biomarker for human cancers. However, results are still inconsistent. We therefore performed a meta-analysis to evaluate the predictive role of miR-17-92 family in human cancer prognosis. We searched literatures published before March 31th, 2017 inPubMed, Cochrane and Embase databases. Twenty six studies were included in our analyses. The overall hazard ratios (HRs) showed that high expression level of miR-17-92 family was a predictor of poor overall survival (OS): adjusted HRs = 1.71, 95% confidence intervals (CIs): 1.39-2.11, p < 0.00001, and poor disease-free survival (DFS): adjusted HRs = 2.29, 95% CIs: 1.41-3.72, p = 0.0008. However, no association between miR-17-92 family expression and cancer progress-free survival (PFS) was found (p > 0.05). Subgroup analyses showed that high expression of miR-17-92 family was associated with poor OS (adjusted HRs = 1.89, 95% CIs: 1.43-2.49, p < 0.00001) and DFS (adjusted HRs = 2.83, 95% CIs: 1.59-5.04, p = 0.0003) among the Asian, and no association was found for the Caucasian (p > 0.05). Besides, the HRs of miR-17-92 family high expression in tissue and serum samples was 1.68 (1.35-2.09) and 2.20 (1.08-4.46) for OS, and 1.73 (0.80-3.74) and 3.37 (2.25-5.02) for DFS. It also found that high expression of miR-17-92 family predicted a poor OS in breast cancer, esophageal squamous cell carcinoma, lymphoma and other cancers. Findings suggest that miR-17-92 family can be an effective predictor for prognosis prediction in cancer patients.
| S-EPMC5620325 | biostudies-literature
Project description:BackgroundTumor associated macrophages (TAMs), a kind of inflammatory cells in the tumor microenvironment, are crucial for the occurrence and development of various tumors which increased the expression of CD163. Nevertheless, not much has been established regarding soluble CD163 and its connection to tumor diagnosis. In this case, a meta-analysis was conducted to determine the tumor diagnostic importance of serum sCD163.MethodsIn order to assess the correlation between sCD163 and the overall survival (OS) or progression-free survival (PFS) among tumor patients, a systematic perusal of literature published until June 2020 was conducted. Relevant data were primarily obtained from papers that have the following qualifications: 1) a confidence interval (CI) of 95%; 2) a report of the hazard ratios; and, 3) pooled by means of the Mantel-Haenszel random-effect representation.ResultsFor the final meta-analysis, eight papers comprised of 1,236 cases were involved. Through pooled investigation, it was determined that a correlation exists between elevated serum sCD163 and worse OS (HR = 2.24, 95% CI: 1.50-3.35, P < 0.001) and PFS (HR = 3.90, 95% CI: 2.33-6.52, P < 0.001) among tumor cases. Subgroup analysis stratified by medium age at diagnosis demonstrated that patients over 60 years old with high sCD163 had worse OS (HR 2.28, 95% CI: 1.58-3.29, P < 0.001) than under 60 (HR 1.43, 95% CI: 1.15-1.77, P = 0.001). Subgroup analysis revealed that analysis method and medium age at diagnosis were the potential source of heterogeneity.ConclusionsOverall, diagnosis of tumor cases can be adversely determined through substantial sCD163 levels. Consequently, it is encouraged that extensive researches regarding the rates of cancer survival be accomplished.
| S-EPMC7683770 | biostudies-literature
Project description:BACKGROUND:Tumor-infiltrating lymphocytes (TIL) in tumour stroma are considered to be involved in the elimination of malignant cells and prevention of metastasis formation. TIL consist of T lymphocytes including cytotoxic lymphocytes that are a constituent part of the effector mechanism of anti-tumour immunity and B lymphocytes that can form tertiary lymphoid structures (TLS). TLS has been described in several solid tumours and colorectal carcinoma (CRC), and the influence on the local and systemic anti-cancer response. AIM:This study aimed to quantify the presence of TLS in CRC patients and to determine their role in tumour progression. PATIENTS AND METHODS:The study included 103 patients with CRC who underwent surgery at the University Clinic of Digestive Surgery in Skopje, whose operative material was analysed at the Institute of Pathology, Medical Faculty in Skopje. The density of TLS was determined and correlated with the neoplasm status of local growth (T), positive lymph nodes, lymphatic invasion, and stage of the disease and tumour grade. RESULTS:The density of TLS was significantly higher in patients with higher stage, lower T status, and negative lymph nodes, in patients with no lymphatic invasion and with better-differentiated tumours. CONCLUSION:The density of TLS plays an important role in controlling the tumour growth, and it can be a parameter for neoplasm progression in CRC patients. The density of TLS influences the control of tumour progression.
| S-EPMC6236051 | biostudies-other