Dataset Information

High expression of fibronectin 1 indicates poor prognosis in gastric cancer.

ABSTRACT: Fibronectin 1 (FN1) is involved in the occurrence and development of various tumors and is upregulated in multiple cancer types. FN1 has been demonstrated to promote cell proliferation and migration in gastric cancer cell lines. However, the relationship between the expression of FN1 and clinicopathological factors and prognosis is not clear in gastric cancer (GC). The aim of the present study was to investigate the association between FN1 expression and clinicopathology and prognosis of gastric cancer. In this study, 17 publicly available GC cohorts (n=2,376) with gene expression data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine databases were tested. In addition, FN1 protein expression was validated by immunohistochemistry in a separate cohort (n=190). The meta-analysis results demonstrated an increase in FN1 expression at the protein and mRNA level in GC tissues, and the FN1 gene was highly expressed at the mRNA level in the advanced T stage (T2 + T3 + T4) group compared with that in the early T stage (T1) group. In addition, the expression of epithelial FN1 at the protein level was positively correlated with tumor size. FN1 expression at the protein and mRNA level was a predictor of poor prognosis following radical resection of GC. In conclusion, the expression of FN1 in GC tissues is upregulated compared with adjacent normal tissues, and it is a potential biomarker of poor prognosis in patients with GC.

SUBMITTER: Sun Y

PROVIDER: S-EPMC6923922 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High expression of fibronectin 1 indicates poor prognosis in gastric cancer.

Sun Yang Y Zhao Chunlin C Ye Yanwei Y Wang Zhen Z He Yuanhang Y Li Yulin Y Mao Haoxun H

Oncology letters 20191113 1

Fibronectin 1 (FN1) is involved in the occurrence and development of various tumors and is upregulated in multiple cancer types. FN1 has been demonstrated to promote cell proliferation and migration in gastric cancer cell lines. However, the relationship between the expression of FN1 and clinicopathological factors and prognosis is not clear in gastric cancer (GC). The aim of the present study was to investigate the association between FN1 expression and clinicopathol ...[more]

PMID: 31897119

Similar Datasets

Project description:BackgroundMethylated DNA in fluids may be a suitable biomarker for cancer patients. XAF1 has been shown to be frequently down-regulated in human gastric cancer (GC). Here, we investigated if XAF1 methylation in GC could be a useful biomarker.MethodsReal-time RT-PCR was used to detect XAF1 mRNA expression; immunohistochemistry and western blot were used to examine XAF1 protein expression in GC tissues (n = 202) and their corresponding para-cancerous histological normal tissues (PCHNTs). Real-time methylation specific-PCR was used to investigate XAF1 promoter methylation in the same panel of GC tissues, their PCHNTs and sera.ResultsWe confirmed frequent XAF1 down-regulation in both mRNA and protein levels in GC tissues as compared to normal controls and PCHNTs. XAF1 hypermethylation was evidenced in 83.2% (168/202) of GC tissues and 27.2% (55/202) of PCHNTs, while no methylation was detected in the 88 normal controls. The methylation level in GC tissues was significantly higher than that in PCHNTs (p<0.05). The hypermethylation of XAF1 significantly correlated with the down-regulation of XAF1 in GC tissues in both mRNA and protein levels (p<0.001 each). Moreover, we detected high frequency of XAF1 methylation (69.8%, 141 out of 202) in the sera DNAs from the same patients, while the sera DNAs from 88 non-tumor controls were negative for XAF1 methylation. The XAF1 methylation in both GC tissues and in the sera could be a good biomarker for diagnosis of GC (AUC = 0.85 for tissue and AUC = 0.91 for sera) and significantly correlated with poorer prognosis (p<0.001). In addition, after-surgery negative-to-positive transition of XAF1 methylation in sera strongly associated with tumor recurrence.Conclusions1) Dysfunction of XAF1 is frequent and is regulated through XAF1 promoter hypermethylation; 2) Detection of circulating methylated XAF1 DNAs in the serum may be a useful biomarker in diagnosis, evaluating patient's outcome (prognosis and recurrence) for GC patients.

Project description:The switching/sucrose non-fermenting (SWI/SNF) chromatin remodeling complexes use the energy of ATP hydrolysis to remodel nucleosomes and modulate transcription, which plays an important role in tumors by regulating epigenetics. SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily C, Member 1 (SMARCC1) has dual roles in tumors but its role in gastric cancer remains unclear. This study was aimed to find the role of SMARCC1 in gastric cancer. SMARCC1 expression across various tumors from The Cancer Genome Atlas was analyzed using TIMER 2.0 (http://timer.comp-genomics.org/). SMARCC1 mRNA expression profiles in gastric cell lines and gastric tissues were compared with normal tissues and analyzed in the Cancer Cell Line Encyclopedia, Oncomine, and Gene Expression Omnibus databases. SMARCC1 mRNA and protein were then examined in fresh gastric cancer tissues and compared with adjacent normal tissues using quantitative real-time PCR, western blotting, and immunohistochemistry. Associations between SMARCC1 expression and clinicopathological factors, overall survival, and disease-free survival were further evaluated using 130 gastric cancer samples harvested from patients after radical total gastrectomy or subtotal gastrectomy at the Xiangya Hospital of Central South University (Changsha, China). SMARCC1 was frequently upregulated in gastric cancer cells and tissues. SMARCC1 overexpression was significantly associated with tumor size (P=0.002), differentiation (P=0.006), depth of invasion (P=0.001), lymph node involvement (P=0.016), and TNM stage (P=0.007). Furthermore, univariate and multivariate Cox analysis revealed that high SMARCC1 expression, depth invasion, lymph node involvement, and TNM stage were independent risk factors for both overall and disease-free survival in gastric cancer patients (all P<0.05). Kaplan-Meier survival analysis revealed that high SMARCC1 expression predicted poor prognosis in gastric cancer patients (P<0.01). High SMARCC1 expression contributes to poor prognosis in gastric cancer patients. SMARCC1 may be a prognostic biomarker and therapeutic target in gastric cancer.

Project description:P53-induced gene 11 (PIG11) is an early transcription-related target of p53 that is involved in cell apoptosis and tumor development. However, its biological function in gastric cancer (GC) tissues and relationship with the prognosis of patients with GC have remained elusive. In the present retrospective study, 60 fresh and 790 paraffin-embedded samples of GC were obtained from the Affiliated Hospital of Nantong University (Nantong, China) with complete clinical data from all patients. Reverse transcription-quantitative PCR and tissue microarray-immunohistochemical analysis were used to determine the expression of PIG11 in the respective GC tissues. A receiver operating characteristic (ROC) curve was plotted to determine the diagnostic utility of PIG11 expression in GC. Furthermore, three online databases, including Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine and Kaplan-Meier plotter, were used for bioinformatics analysis of PIG11. PIG11 expression in GC tissues was high, which was positively correlated with invasive depth (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.019), TNM staging (P<0.001) and carcinoembryonic antigen in serum (P<0.001), and negatively associated with the overall survival of patients with GC. The ROC curve analysis suggested that based on PIG11 expression, it was possible to distinguish GC tissues from adjacent normal tissues (P<0.0001) with a sensitivity and specificity of 81.67 and 76.67%, respectively. In addition, Cox logistic regression analysis demonstrated that high PIG11 expression is a novel biomarker for unfavorable prognosis of patients with GC. Furthermore, the results obtained from the GEPIA database indicated that PIG11 expression is correlated with TNF, carcinoembryonic antigen related cell adhesion molecule 5, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha, VEGFA and kinase insert domain receptor. Therefore, PIG11 expression may be associated with the malignancy of GC and may serve as a potential diagnostic and prognostic biomarker for GC.

Project description:BackgroundGastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Long noncoding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. Although downregulation of lncRNA GAS5 (Growth Arrest-Specific Transcript) in several cancers has been studied, its role in gastric cancer remains unknown. Our studies were designed to investigate the expression, biological role and clinical significance of GAS5 in gastric cancer.MethodsExpression of GAS5 was analyzed in 89 gastric cancer tissues and five gastric cancer cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of GAS5. The effect of GAS5 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by hochest stainning. Gastric cancer cells transfected with pCDNA3.1 -GAS5 were injected into nude mice to study the effect of GAS5 on tumorigenesis in vivo. Protein levels of GAS5 targets were determined by western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed).ResultsWe found that GAS5 expression was markedly downregulated in gastric cancer tissues, and associated with larger tumor size and advanced pathologic stage. Patients with low GAS5 expression level had poorer disease-free survival (DFS; P = 0.001) and overall survival (OS; P < 0.001) than those with high GAS5 expression. Further multivariable Cox regression analysis suggested that decreased GAS5 was an independent prognostic indicator for this disease (P = 0.006, HR = 0.412; 95%CI = 2.218-0.766). Moreover, ectopic expression of GAS5 was demonstrated to decrease gastric cancer cell proliferation and induce apoptosis in vitro and in vivo, while downregulation of endogenous GAS5 could promote cell proliferation. Finally, we found that GAS5 could influence gastric cancer cells proliferation, partly via regulating E2F1 and P21 expression.ConclusionOur study presents that GAS5 is significantly downregulated in gastric cancer tissues and may represent a new marker of poor prognosis and a potential therapeutic target for gastric cancer intervention.

Dataset Information

High expression of fibronectin 1 indicates poor prognosis in gastric cancer.

Publications

High expression of fibronectin 1 indicates poor prognosis in gastric cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets