Notch2 as a promising prognostic biomarker for oesophageal squamous cell carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang C
PROVIDER: S-EPMC4860585 | biostudies-other | 2016
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BackgroundOur previous study found that dysregulated microRNA-146a-5p (miR-146a-5p) is involved in oesophageal squamous cell cancer (ESCC) proliferation. This article aimed to evaluate its detailed mechanisms in ESCC epithelial-mesenchymal transition (EMT) progression.MethodsInvasion assay, qRT-PCR and western blotting were used to validate the roles of miR-146a-5p and Notch2 in EMT progression. miRNA target gene prediction databases and dual-luciferase reporter assay were used to validate the target gene.ResultsmiR-146a-5p inhibitor led to increase of invaded ESCC cells, while miR-146a-5p mimics inhibited invasion ability of ESCC cells. Protein level of E-cadherin decreased, whereas those of Snail and Vimentin increased in the anti-miR-146a-5p group, which demonstrated that miR-146a-5p inhibits EMT progression of ESCC cells. miRNA target gene prediction databases indicated the potential of Notch2 as a direct target gene of miR-146a-5p and dual-luciferase reporter assay validated it. Importantly, shRNA-Notch2 restrained EMT and partially abrogated the inhibiting effects of miR-146a-5p on EMT progression of ESCC cells.ConclusionsmiR-146a-5p functions as a tumour-suppressive miRNA targeting Notch2 and inhibits the EMT progression of ESCC.
| S-EPMC5155362 | biostudies-literature
Project description:BackgroundGABRP has been reported to play an oncogenic role in various carcinomas. However, no report has been found for its involvement in lung squamous cell carcinoma (LUSC) development yet. We aimed to explore the expression and prognostic roles of GABRP and assessment of its association with tumor microenvironment in LUSC.MethodsThe GABRP expression in LUSC was analyzed using TCGA, GEO, and HPA databases. The Kaplan-Meier, Cox regression analysis, and receiver operating characteristic (ROC) curve were applied to assess the prognostic and diagnostic values of GABRP in LUSC. We also performed ESTIMATE and ssGSEA to explore the association between GABRP expression and immune cell infiltrations. GABRP was highly expressed in LUSC patients, and up-regulation of GABRP was associated with shorter overall survival (OS). Cox regression analysis indicated that GABRP was an independent prognostic factor for LUSC patients. KEGG analysis revealed that GABRP may play an important role in starch and sucrose metabolism and nicotine addiction. Specifically, GABRP expression showed significant positive correlations with the infiltration levels of most types of immune cells, as well as immune checkpoint molecules expression.ConclusionUp-regulation of GABRP in LUSC could be severed as a prognostic marker and a potential target for immunotherapy in LUSC.
| S-EPMC10115206 | biostudies-literature
Project description:Survivin, a new member of the family of apoptosis inhibitors, is expressed almost exclusively in proliferating cells, above all in cancers. Subcellular localisation and prognostic implications of the survivin protein have not yet been determined in oesophageal squamous cell carcinoma. The survival of 84 patients with oesophageal squamous cell carcinomas was correlated with the extent of immunohistochemical survivin expression in tumour cell nuclei. Tumours were scored positive when >5% cells stained positive. Patients were followed up for at least 5 years or until death. In normal oesophageal squamous cell epithelium, some cytoplasmic survivin expression was detected in the basal cells, whereas proliferating cells showed nuclear staining of survivin. Nuclear expression of survivin was also detected in 67 cancers (80%). The mean survival for patients of this group (28 months, range 20-36) was significantly less than that for patients without survivin expression in the tumour cell nuclei (108 months, range 62-154, P=0.003). Using univariate analysis, nuclear survivin expression (P=0.003), tumour depth (P=0.001), lymph node metastasis (P=0.003) and stage (P<0.001) were the best predictors of survival. In contrast, cytoplasmic survivin staining was noted in 53 (63%) tumours and had no prognostic relevance. In conclusion, the analysis of nuclear survivin expression identifies subgroups in oesophageal squamous cell cancer with favourable (survivin(-)) or with poor prognosis (survivin(+)). We suggest that the determination of nuclear survivin expression could be used to individualise therapeutic strategies in oesophageal squamous cell cancer in the future.
| S-EPMC2376783 | biostudies-other
Project description:Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck. In OSCC patients, the prognosis was dramatically different. In this research, we aimed to study the expressions and prognostic values of IgG Fc binding protein (FCGBP) in OSCC patients. The expression of FCGBP was analyzed using TCGA datasets and GEO datasets. FCGBP was evaluated for its predictive significance in OSCC patients by the use of a Kaplan-Meier and Cox regression model. Enrichment analysis for the GO and KEGG databases were conducted. CIBERSORT used TCGA datasets to show immune cell infiltration. In addition, researchers looked into the relationships between FCGBP and immune cells. The levels of FCGBP in OSCC cells was examined through the use of RT-PCR. FCGBP overexpression was tested for its effects on OSCC cell proliferation and invasion using CCK-8 and Transwell assays. We observed that FCGBP expressions were distinctly downregulated in OSCC specimens compared with nontumor tissues in both TCGA and GEO datasets, which was further confirmed by RT-PCR. OSCC patients with advanced clinical stages and poor prognoses had lower levels of FCGBP expression. Many immune-related biological activities and signaling pathways were found to be considerably abundant in KEGG tests and GO analysis results. The correlation analysis indicated that FCGBP was associated with a number of immune cells in a positive way. We found that FCGBP expressions were strongly and distinctly linked to the expressions of known immunological checkpoints, and FCGBP expression had significant positive connections with tumor mutational burden. FCGBP upregulation distinctly slowed the growth and invasion of OSCC cells in functional experiments. FCGBP has the potential to be a therapeutic target for OSCC and a biomarker for OSCC patients' prognosis.
| S-EPMC9207623 | biostudies-literature
Project description:BackgroundThere are few data evaluating the extent of downstaging in patients with oesophageal adenocarcinoma and oesophageal squamous cell carcinoma and the difference in outcomes for a similar pathological stage in neoadjuvant-naive patients. The aim of this study was to characterize the prognostic value of downstaging extent in patients receiving neoadjuvant therapy for oesophageal cancer.MethodsOesophageal adenocarcinoma and oesophageal squamous cell carcinoma patients receiving either neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy between 2004 and 2017 were identified from the National Cancer Database. The extent of downstaging was defined as the extent of migration between groups (for example stage IVa to IIIb = one stage). Cox multivariable regression was used to produce adjusted models for downstaging extent.ResultsOf 13 594 patients, 11 355 with oesophageal adenocarcinoma and 2239 with oesophageal squamous cell carcinoma were included. In oesophageal adenocarcinoma, patients with downstaged disease by three or more stages (hazards ratio (HR) 0.40, 95 per cent c.i. 0.36 to 0.44, P < 0.001), two stages (HR 0.43, 95 per cent c.i. 0.39 to 0.48, P < 0.001), or one stage (HR 0.57, 95 per cent c.i. 0.52 to 0.62, P < 0.001) had significantly longer survival than those with upstaged disease in adjusted analyses. In oesophageal squamous cell carcinoma, patients with downstaged disease by three or more stages had significantly longer survival than those with less downstaged disease, no change, or upstaged disease. Patients with downstaged disease by three or more stages (HR 0.55, 95 per cent c.i. 0.43 to 0.71, P < 0.001), two stages (HR 0.58, 95 per cent c.i. 0.46 to 0.73, P < 0.001), or one stage (HR 0.69, 95 per cent c.i. 0.55 to 0.86, P = 0.001) had significantly longer survival than those with upstaged disease in adjusted analyses.ConclusionThe extent of downstaging is an important prognosticator, whereas the optimal neoadjuvant therapy remains controversial. Identifying biomarkers associated with response to neoadjuvant regimens may permit individualized treatment.
| S-EPMC10282921 | biostudies-literature
Project description:Background and aimCirculating microRNAs (miRNAs) are potential biomarkers for cancer detection; however, little is known about their prognostic impact on oesophageal squamous cell carcinoma (ESCC). The current study aims to uncover novel miRNAs for prognostic biomarkers in ESCC patients.Patients and methodsWe initially screened the expression of 754 serum miRNAs using TaqMan Low Density Array in two pooled samples respectively from 28 ESCC and 28 normal controls. Markedly upregulated miRNAs in ESCC and some miRNAs reported to be differently expressed in ESCC tissue were then validated individually by RT-qPCR in another 83 patients and 83 controls arranged in two phases. The changes of the selected miRNAs during the esophagectomy and their prognostic value were examined.ResultsSeven serum miRNAs were found to be significantly higher in ESCC than in controls; namely, miR-25, miR-100, miR-193-3p, miR-194, miR-223, miR-337-5p and miR-483-5p (P<0.0001), and the area under the receiver-operating-characteristic (ROC) curve (AUC) for the seven-miRNA panel was 0.83 (95% CI 0.75-0.90). Most of these miRNAs declined markedly in postoperative samples versus preoperative samples (P<0.05). Moreover, high level of miR-25 was significantly correlated with shorter overall survival in patients (P = 0.027). Cox regression analysis identified lymph node metastasis, miR-25 and miR-100 as the independent risk factors for overall survival (hazard ratio (HR) 2.98 [1.36-6.55], P = 0.006; HR 3.84 [1.02-14.41], P = 0.029; HR 4.18 [1.21-14.50], P = 0.024, respectively).ConclusionThe seven serum miRNAs could potentially serve as novel biomarkers for ESCC; moreover, specific miRNAs such as miR-25 and miR-100 can predict poor survival in ESCC.
| S-EPMC3961321 | biostudies-literature
Project description:Till now, no appropriate biomarkers for high-risk population screening and prognosis prediction have been identified for patients with oesophageal squamous cell carcinoma (ESCC). In this study, by the combined use of data from the Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA)-oesophageal carcinoma (ESCA), we aimed to screen dysregulated genes with prognostic value in ESCC and the genetic and epigenetic alterations underlying the dysregulation. About 222 genes that had at least fourfold change in ESCC compared with adjacent normal tissues were identified using the microarray data in GDS3838. Among these genes, only PDLIM2 was associated with nodal invasion and overall survival (OS) at the same time. The high PDLIM2 expression group had significantly longer OS and its expression was independently associated with better OS (HR: 0.64, 95% CI: 0.43-0.95, P = 0.03), after adjustment for gender and pathologic stages. The expression of its exon 7/8/9/10 had the highest AUC value (0.724) and better prognostic value (HR: 0.43, 95% CI: 0.22-0.83, P = 0.01) than total PDLIM2 expression. PDLIM2 DNA copy deletion was common in ESCC and was associated with decreased gene expression. The methylation status of two CpG sites (cg23696886 and cg20449614) in the proximal promoter region of PDLIM2 showed a moderate negative correlation with the gene expression in PDLIM2 copy neutral/amplification group. In conclusion, we infer that PDLIM2 expression might be a novel prognostic indicator for ESCC patients. Its exon 7/8/9/10 expression had the best prognostic value. Its down-regulation might be associated with gene-level copy deletion and promoter hypermethylation.
| S-EPMC6653303 | biostudies-literature
Project description:Background and aimsMicroRNAs including miR146a have a regulatory role on the expression of genes and act with binding to 3'-UTR region of the genes. Cyclooxygenase-2 (COX-2) is involved in carcinogenesis as an inflammatory marker, and microRNA-146a (miR-146a) as a negative regulatory factor. We aimed to evaluate miR146a expression as a prognostic or diagnostic biomarker for esophageal squamous cell carcinoma (ESCC) and also an association between miR146a and COX2 expression.Materials and methodsWe quantified the level of miR-146a and COX-2 expression in cancerous and adjacent normal tissue samples obtained from 34 patients with ESCC, using real-time-PCR. Statistical analyses were conducted using one-sample t-test. Receiver-operating characteristic (ROC) curve and Kaplan-Meier analysis were applied to assay miR146a as a diagnostic and prognostic marker, respectively, during 4 years of the study. Furthermore, the Cox regression model was performed to assay the hazard ratio (HR). The association between miR-146a and COX2 expression level in ESCC patients was evaluated by nonparametric Spearman's rho analysis.ResultsThe results revealed a reduction of miR-146a expression in 50% of cancerous tissue when compared with adjacent normal regions (P-value=0.127). COX-2 expression in 80% of ESCC patients was higher than in the controls (P-value=0.001). Overall, in 60% of cases, direct association was seen between microRNA-146a and COX-2 expression level (correlation coefficient= 0.438, P-value=0.011). COX2 can be considered as a diagnostic biomarker (AUC=0.834, sensitivity=72%, specificity =83%, P-value<0.0001) but miR146a cannot be considered as a diagnostic biomarker (AUC=0.553, sensitivity=88%, specificity =28%, P-value=0.453). Survival analysis by Kaplan-Meier method showed miR146a and COX2 expression can be probably considered as prognostic biomarkers for ESCC because patients with high expression of miR146a had 7 months shorter life span and patients with low expression of COX2 had 8 months shorter life span.ConclusionCOX2 expression is a diagnostic biomarker. MiR-146a and COX2 expression can probably be considered as prognostic biomarkers for survival in ESCC.
| S-EPMC7023856 | biostudies-literature
Project description:AimThe main of the present study was to investigate the role of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in oral squamous cell carcinoma (OSCC) with the overarching of providing new biomarkers or potential therapeutic targets for OSCC.MethodsWe combined datasets downloaded from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and samples collected from the clinic to evaluate the expression of IGF2BP2 in OSCC. IGF2BP2 survival analysis was respectively performed based on TCGA, GEO, and clinical samples. Correlations between IGF2BP2 expression and clinicopathological parameters were then analyzed, and signaling pathways associated with IGF2BP2 expression were identified using gene set enrichment analysis (GSEA 4.1.0). Moreover, an IGF2BP2 co-expressed gene network was constructed, followed by gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on IGF2BP2 co-expressed genes. Finally, TIMER and CIBERSORT were used to analyze the correlations among IGF2BP2, IGF2BP2-coexpressed genes, and tumor-infiltrating immune cells (TICs).ResultsIGF2BP2 was highly expressed in OSCC and significantly correlated with overall survival of OSCC patients (P<0.01). High IGF2BP2 expression correlated with poor overall survival. The GSEA results showed that cell apoptosis-, tumor-, and immune-related pathways were significantly enriched in samples with high IGF2BP2 expression. Furthermore, GO and KEGG enrichment analyses results of IGF2BP2 co-expressed genes indicated that these genes are mainly associated with immunity/inflammation and tumorigenesis. In addition, IGF2BP2 and its co-expressed genes are associated with TICs (P<0.01).ConclusionIGF2BP2 may be a potential prognostic biomarker in OSCC and correlates with immune infiltrates.
| S-EPMC8859425 | biostudies-literature
Project description:Chromosomal instability (CIN) plays a key role in the carcinogenesis of several human cancers and can be related to the deregulation of core components of the spindle assembly checkpoint (SAC) including BUBR1 protein kinase. These proteins have been related to tumor development and poor survival rates in human patients with oral squamous cell carcinoma (OSCC). To investigate the expression of the SAC proteins BUBR1, BUB3 and SPINDLY and also Ki-67 in canine OSCC, we performed an immunohistochemical evaluation in 60 canine OSCCs and compared them with clinical and pathological variables. BUBR1, Ki-67, BUB3 and SPINDLY protein expressions were detected in all cases and classified as with a high-expression extent score in 31 (51.7%) cases for BUBR1, 33 (58.9%) cases for BUB3 and 28 (50.9%) cases for SPINDLY. Ki-67 high expression was observed in 14 (25%) cases. An independent prognostic value for BUBR1 was found, where high BUBR1 expression was associated with lower survival (p = 0.012). These results indicate that BUBR1 expression is an independent prognostic factor in these tumors, suggesting the potential use for clinical applications as a prognostic biomarker and also as a pharmacological target in canine OSCC.
| S-EPMC9687056 | biostudies-literature