Elevated heparanase expression is associated with poor prognosis in breast cancer: a study based on systematic review and TCGA data.
Ontology highlight
ABSTRACT:
SUBMITTER: Sun X
PROVIDER: S-EPMC5522166 | biostudies-other | 2017 Jun
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Breast cancer is the most commonly diagnosed type of cancer and one of the leading causes of cancer-associated mortality in women. In addition, the underlying molecular mechanisms of the occurrence and development of breast cancer requires further investigation. In the present study, bioinformatics analysis was performed to identify differentially expressed genes (DEGs) between breast cancer and normal breast tissues to investigate the underlying molecular mechanisms. In addition, reverse transcription-quantitative PCR and immunohistochemistry (IHC) were performed to investigate the protein and mRNA expression levels of a specific DEG, discs large-associated protein 5 (DLGAP5). A Cell Counting Kit-8 assay and flow cytometry analysis were used to assess the effects of DLGAP5 on cell proliferation. In total, 85 DEGs were identified in the three Gene Expression Omnibus datasets, including 40 upregulated and 45 downregulated genes. In addition, 30 hub genes were identified following the construction of a protein-protein interaction network, and 28 of the 30 hub genes were established to be indicators of breast cancer prognosis. DLGAP5 was highly expressed in breast cancer specimens, and its expression levels were correlated with clinical stage and lymph node status. In addition, downregulation of DLGAP5 repressed the proliferation of breast cancer MDA-MB-231 cells and induced cell cycle arrest. Additionally, DLGAP5 was identified to be localized in the mitochondria, and the presence of a conserved microtubule-associated proteins 1A/1B light chain 3B-interacting region motif suggested that DLGAP5 may serve a role in mitophagy. The present results demonstrated an association between DLGAP5 expression levels and the clinicopathological characteristics of patients with breast cancer using IHC. In conclusion, DLGAP5 may be a promising target in the diagnosis and treatment of breast cancer.
| S-EPMC7204629 | biostudies-literature
Project description:Numerous studies have investigated the prognostic role of YKL-40 in breast cancer, but yielded inconsistent results. To derive a more precise evaluation, relevant publications assessing the association between YKL-40 expression and clinical outcome of breast cancer patients were electronically searched and identified. A combined analysis of included studies was performed using fixed- or random-effect model to calculate the pooled hazard ratio (HR) or odds ratio(OR) and 95% confidence interval (95%CI) for the assessment of the association. Ten eligible studies involving 1250 patients were ultimately included in the meta-analysis. Overall, the pooled analysis showed that elevated YKL-40 expression was significantly associated with a poor overall survival(OS: HR=1.48, 95%CI= 1.11-1.97) and disease-free survival(DFS: HR=1.51, 95%CI= 1.10-2.07). The subgroup analysis by detection methods revealed an unfavorable OS in breast cancer patients with elevated YKL-40 expression evaluated by IHC(HR=1.39, 95%CI=1.12-1.71) but not by ELISA/RIA. Also, the stratification analysis by ethnicity showed a significant association between increased YKL-40 expression and shorter OS of breast cancer patients in western population(HR=1.51, 95%CI=1.03-2.21) as well as Asian population (HR=1.40, 95%CI= 1.05-1.86). Similarly, the subgroup analysis by detection methods revealed a significantly inferior DFS in breast cancer patients with increased YKL-40 expression disregarding the use of IHC(HR=2.02, 95%CI=1.47-2.79) or ELISA/RIA(HR=1.06, 95%CI= 1.02 -1.10). Additionally, increased YKL-40 expression was found to significantly correlate with larger tumor size (OR=2.38, 95%CI=1.41-4.05).The present meta-analysis indicate that elevated YKL-40 expression is associated with a poor prognosis in breast cancer patients. YKL-40 may serve as a promising predictive biomarker of prognosis of breast cancer.
| S-EPMC5354916 | biostudies-literature
Project description:BACKGROUND:The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma (HCC) remains unknown. Our study aimed to investigate the role and clinical significance of E2F2 in HCC. METHODS:HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression were applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier were employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene Set Enrichment Analysis (GSEA). RESULTS:The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR?=?2.62 for G3-4 vs. G1-2, p?=?1.80E-05), clinical stage (OR?=?1.74 for III-IV vs. I-II, p?=?0.03), T (OR?=?1.64 for T3-4 vs.T1-2, p?=?0.04), tumor status (OR?=?1.88 for with tumor vs. tumor free, p?=?3.79E-03), plasma alpha fetoprotein (AFP) value (OR?=?3.18 for AFP???400 vs AFP<20, p?=?2.16E-04; OR?=?2.50 for 20???AFP<400 vs AFP<20, p?=?2.56E-03). Increased E2F2 had an unfavorable OS (p?=?7.468e-?05), PFI (p?=?3.183e-?05), DFI (p?=?0.001), DSS (p?=?4.172e-?05). Elevated E2F2 was independently bound up with OS (p?=?0.004, hazard ratio [HR]?=?2.4 (95% CI [1.3-4.2])), DFI (P?=?0.029, hazard ratio [HR]?=?2.0 (95% CI [1.1-3.7])) and PFI (P?=?0.005, hazard ratio [HR]?=?2.2 (95% CI [1.3-3.9])). GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signaling pathway, nucleotide excision repair, ubiquitin-mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype. CONCLUSIONS:Elevated E2F2 can be a promising independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signaling pathway, ubiquitin-mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participates in the initial and progression of HCC.
| S-EPMC7594443 | biostudies-literature
Project description:Breast cancer is the second most common malignancy in women and considered as a severe health burden. PEG3 mutations have been observed in several cancers. However, the associations of PEG3 mutation with tumor mutation burden (TMB) and prognosis in breast cancer have not been investigated. In our study, the somatic mutation data of 986 breast cancer patients from The Cancer Genome Atlas (TCGA) were analyzed. It showed that PEG3 had a relatively high mutation rate (2%). After calculated the TMB in PEG3 mutant and PEG3 wild-type groups, we found the TMB value was significantly higher in PEG3 mutant samples than that in PEG3 wild-type samples (P = 5.6e-07), which was independent of the confounding factors including age, stage, mutations of BRCA1, BRCA2 and POLE (odd ratio, 0.45; 95% CI, 0.20-0.98; P=0.044). Survival analysis revealed that PEG3 mutant samples had inferior survival outcome compared with the PEG3 wild-type samples after adjusted for the confounding factors above (hazard ratio, 0.27; 95% CI: 0.12-0.57; P<0.001). These results illustrated that PEG3 mutation was associated with high TMB and inferior prognosis, suggesting PEG3 mutation might play a guiding role in prognosis prediction and immunotherapy selection in breast cancer.
| S-EPMC7419805 | biostudies-literature
Project description:BackgroundThe epigenetic abnormality of tumor-associated genes contributes to the pathogenesis of colorectal carcinoma (CRC). However, methylation in colorectal cancer is still poorly characterized.MethodBy integration of DNA methylation data from the GEO database and gene expression data from The Cancer Genome Atlas database, the aberrantly methylated genes involved in CRC tumorigenesis were identified. Subsequent in vitro experiments further validated their role in CRC.ResultsWe performed integrative genomic analysis and identified HPSE2, a novel tumor suppressor gene that is frequently inactivated through promoter methylation in CRC. K-M survival analysis showed that hypermethylation-low expression of heparanase 2 (HPSE2) was related to poor patient prognosis. Overexpression of HPSE2 reduced cell proliferation in vivo and in vitro. HPSE2 could regulate the p53 signaling pathway to block the cell cycle in G1 phase.ConclusionHPSE2, a novel tumor suppressor gene that is frequently inactivated through promoter methylation in CRC. HPSE2 performs a tumor suppressive function by activating the p53/ p21 signaling cascade. The promoter hypermethylation of HPSE2 is a potential therapeutic target in patients with CRC, especially those with late-stage CRC.
| S-EPMC7934273 | biostudies-literature
Project description:BackgroundBCDIN3D is a member of the Bin3 methyl-transferase family that targets the 5' mono-phosphate of nucleic acids. Although BCDIN3D has been shown to increase tumorigenic phenotypes and invasiveness in MDA-MB-231 cells, its the clinical implications in breast cancer remain unclear.MethodsWe screened for BCDIN3D using tissue microarrays constructed from 250 patients who were histologically confirmed to have invasive ductal breast carcinoma at the Fudan University Shanghai Cancer Center.ResultsThe survival analysis by Kaplan-Meier and Cox regression showed that BCDIN3D expression level served as a prognostic factor for disease-free survival (P = 0.042). The prognostic value of BCDIN3D was most significant in triple-negative breast cancer (TNBC) patients (P = 0.007).ConclusionsBCDIN3D might serve as an important prognostic factor for TNBC patients.
| S-EPMC5288229 | biostudies-literature
Project description:INTRODUCTION:Mitigating the transition from acute to chronic whiplash-associated disorders (WAD) is fundamental, and this could be achieved through early identification of individuals at risk. Several physical factors such as angular velocity, smoothness of neck movement and coactivation of neck flexors and extensors, have been observed in patients with WAD, but their predictive ability after a whiplash injury have not been considered in previous reviews. Therefore, the aim of the current protocol is to outline the protocol for a systematic review that synthesises the current evidence of which physical factors can predict ongoing pain and disability following a whiplash trauma. METHODS AND ANALYSIS:Two independent reviewers will search for studies in several electronic databases including MEDLINE, Embase, CINAHL, PsycINFO, Scopus and Web of Science as well as grey literature. Observational cohort studies will be considered if they involve participants with acute WAD followed for at least 3 months post-injury. Studies will be required to assess the prognostic ability of one or more physical factors that directly involve a body function and/or structure and can be measured objectively. Further, patient-reported outcomes of physical function will be considered. The primary outcome for this review is Neck Disability Index, while all other validated measures will be considered as secondary outcomes. Risk of bias across individual studies will be assessed using the Quality In Prognostic Studies tool along with the Grades of Recommendation, Assessment, Development and Evaluation method to assess the quality of evidence. A meta-analysis will be conducted depending on homogeneity and the number of available studies. If appropriate, data will be pooled and presented as odds ratios, otherwise, a qualitative synthesis will be conducted. ETHICS AND DISSEMINATION:Ethical approval is not required for this systematic review. The result from this review will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER:CRD42019122559.
| S-EPMC6887082 | biostudies-literature
Project description:Cystatin SN (CST1) belongs to the type 2 cystatin (CST) superfamily, which restricts the proteolytic activities of cysteine proteases. CST1 has been recently considered to be involved in the development of several human cancers. However, the prognostic significance and function of CST1 in breast cancer remains unknown. In the current study, we found that CST1 was generally upregulated in breast cancer at both mRNA and protein level. Furthermore, overall survival (OS) and disease-free survival (DFS) in the low CST1 expression subgroup were significantly superior to the high CST1 expression subgroup (OS, p < 0.001; DFS, p < 0.001), which indicated that CST1 expression level was closely correlated to the survival risk of these patients. Univariate and multivariate analyses demonstrated that CST1 expression was an independent prognostic factor, the same as ER status and nodal status. Next, CST1 overexpression promoted breast cancer cell proliferation, clonogenicity, migration, and invasion abilities. By contrast, knockdown of CST1 attenuated these malignant characteristics in breast cancer cells. Collectively, our study indicates that CST1 cannot only serve as a significant prognostic indicator but also as a potential therapeutic target for breast cancer. KEY MESSAGES:High CST1 expression is negatively correlated with survival of breast cancer patients. CST1 promotes cell proliferation, clone formation, and metastasis in breast cancer cells. CST1 is a novel potential prognostic biomarker and therapeutic target for breast cancer.
| S-EPMC5515997 | biostudies-literature
Project description:A number of biomarkers have been identified for various cancers. However, biomarkers associated with glioma remain largely to be explored. In the current study, we investigated the relationship between the expression and prognostic value of the HIST1H2BK gene in glioma. Sequential data filtering (survival analysis, independent prognostic analysis, ROC curve analysis, and clinical correlation analysis) was performed, which resulted in identification of the association between the HIST1H2BK gene and glioma. Then, the HIST1H2BK gene was analyzed using bioinformatics (Kaplan-Meier survival analysis, univariate Cox analysis, multivariate Cox analysis, and ROC curve analysis). The results showed that low expression of HIST1H2BK was associated with better prognosis, and high expression of HIST1H2BK was associated with poor prognosis. In addition, HIST1H2BK was an independent prognostic indicator for patients with glioma. We also evaluated the association between HIST1H2BK and clinical characteristics. Furthermore, gene set enrichment analysis (GSEA) and analysis of immune infiltration were performed. The results showed that HIST1H2BK was associated with intensity of immune infiltration in glioma. Finally, co-expression analysis was performed. The results showed that HIST1H2BK was positively correlated with HIST1H2AG, HIST2H2AA4, HIST1H2BJ, HIST2H2BE, and HIST1H2AC, and negatively correlated with PDZD4, CRY2, GABBR1, rp5-1119a7.17, and KCNJ11. This study showed that upregulation of HIST1H2BK in low-grade glioma (LGG) tissue was an indicator of poor prognosis. Moreover, this study demonstrated that HIST1H2BK may be a promising biomarker for the treatment of LGG.
| S-EPMC7225299 | biostudies-literature
Project description:BackgroundThe elevation of the platelet-to-lymphocyte ratio (PLR), an easily applicable blood test based on platelet and lymphocyte counts has been associated with poor prognosis in patients with different types of cancer. The present study was aimed to investigate the prognostic significance of the preoperative PLR in a large cohort of breast cancer patients.MethodsData from 793 consecutive non-metastatic breast cancer patients, treated between 1999 and 2004, were evaluated retrospectively. The optimal cutoff values for the PLR were calculated using receiver operating curve analysis. Cancer-specific survival (CSS), overall survival (OS) as well as distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of PLR, multivariable Cox regression models were applied for all three different end points.ResultsUnivariable analysis revealed a significant association between the elevated preoperative PLR and CSS (hazard ratio (HR): 2.75, 95% confidence interval (CI): 1.57-4.83, P<0.001) that remained statistically significant in multivariable analysis (HR: 2.03, 95% CI: 1.03-4.02, P=0.042). An increased PLR was also significantly associated with decreased OS in univariable (HR: 2.45, 95% CI: 1.43-4.20, P=0.001) and in multivariable analysis (HR: 1.92, 95% CI: 1.01-3.67, P=0.047). Furthermore, univariable analysis showed a significant impact of increased PLR on DMFS (HR: 2.02, 95% CI: 1.18-3.44, P=0.010). Subgroup analysis revealed significant associations of the elevated PLR on the primary end point CSS for all breast cancer subtypes. This association retained its significance in multivariable analysis in patients with luminal B tumours (HR: 2.538, 95% CI: 1.043-6.177, P=0.040).ConclusionsIn this study, we identified the preoperative PLR as an independent prognostic marker for survival in breast cancer patients. Independent validation of our findings is needed.
| S-EPMC4021515 | biostudies-literature