Project description:Integrin, beta-like 1 (ITGBL1), a β-integrin-related extracellular matrix protein, was found more commonly up-regulated in gastric cancer (GC) by screening and analyzing Gene Expression Omnibus (GEO) and Oncomine databases, reminding us to explore its prognostic significance in GC. In our current study, we observed that ITGBL1 expression was significantly up-regulated in GC compared with normal controls in clinical specimens. In addition, elevated ITGBL1 expression was positively correlated with patients' tumor-node-metastasis (TNM) stage and distant metastasis. Kaplan-Meier analysis indicated that high ITGBL1 expression was significantly associated with shorter survival times in GC patients. Multivariate Cox regression analysis confirmed ITGBL1 expression as an independent prognostic factor in GC. Gene set enrichment analysis (GSEA) of multiple GEO datasets revealed a close relationship between ITGBL1 expression and the KRAS/epithelial-mesenchymal transition (EMT) signaling pathway. In conclusion, these data provide evidences that ITGBL1 is a potential predictor and may be involved in cancer cell invasion and metastasis via inducing EMT, and the ITGBL1-related pathways may represent a novel therapeutic strategy for treatment of GC.
Project description:Although gastric cancer is a common cause of cancer mortality worldwide, its biological heterogeneity limits the available therapeutic options. Therefore, identifying novel therapeutic targets for developing effective targeted therapy of gastric cancer is a pressing need. Here, we investigate molecular function and regulatory mechanisms of Vestigial-like 1 (VGLL1) in gastric cancer. Microarray analysis of 556 gastric cancer tissues revealed that VGLL1 was a prognostic biomarker that correlated with PI3KCA and PI3KCB. VGLL1 regulates the proliferation of gastric cancer cells, as shown in live cell imaging, sphere formation, and in vivo xenograft model. Tail vein injection of NUGC3 cells expressing shVGLL1 resulted in less lung metastasis occurring when compared to the control. In contrast, larger metastatic lesions in lung and liver were detected in the VGLL1-overexpressing NUGC3 cell xenograft excision mouse model. Importantly, VGLL1 expression is transcriptionally regulated by the PI3K-AKT-β-catenin pathway. Subsequently, MMP9, a key molecule in gastric cancer, was explored as one of target genes that were transcribed by VGLL1-TEAD4 complex, a component of the transcription factor. Taken together, PI3K/AKT/β-catenin signaling regulates the transcription of VGLL1, which promotes the proliferation and metastasis in gastric cancer. This finding suggests VGLL1 as a novel prognostic biomarker and a potential therapeutic target.
Project description:Background: Diacylglycerol kinase iota (DGKI) is overexpressed in a variety of cancers and is associated with poor prognosis in colon cancer. This study evaluated the prognostic value of DGKI in gastric cancer (GC) using data from The Cancer Genome Atlas (TCGA). Methods: RNA sequencing results and clinical data of gastric adenoma and adenocarcinoma samples were obtained from the TCGA database (https://portal.gdc.cancer.gov). The Wilcoxon or Kruskal-Wallis test and logistic regression were used to analyze the relationship between DGKI and the clinicopathological characteristics of GC patients. Univariate Cox regression and Kaplan-Meier analysis were used to analyze the clinicopathological characteristics of GC patients and the relationship between DGKI and overall survival time, and multivariate Cox regression analysis was used to identify independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. Results: DGKI was overexpressed in gastric tumors and was related to poor prognosis (p = 0.003). Overexpression of DGKI in GC was significantly correlated with high grade (OR = 1.71 for G3 vs. G2), stage (OR = 2.08 for II vs. I) and T classification (OR = 4.64 for T4 vs. T1; OR = 3.99 for T3 vs. T1; OR = 3.37 for T2 vs. T1) (all p <0.05). DGKI (OR = 7.34; p = 0.000) was an independent risk factor affecting the survival of GC patients. The MAPK signaling pathway was differentially enriched with DGKI overexpression. Conclusion: DGKI overexpression may be a potential molecular marker for poor prognosis in GC. The MAPK signaling pathway may be one of the key pathways related to DGKI regulation in GC.
Project description:Background: The aim of this study was to investigate the prognostic significance of faciogenital dysplasia 6 (FGD6) in gastric cancer (GC). Methods: The data of GC patients from The Cancer Genome Atlas (TCGA) database were used for the primary study. Then, our data were validated by the GEO database and RuiJin cohort. The relationship between the FGD6 level and various clinicopathological features was analyzed by logistic regression and univariate Cox regression. Multivariate Cox regression analysis was used to evaluate whether FGD6 was an independent prognostic factor for survival of patients with GC. The relationship between FGD6 and overall survival time was explored by the Kaplan-Meier method. In addition, gene set enrichment analysis (GSEA) was performed to investigate the possible biological processes of FGD6. Results: The FGD6 level was significantly overexpressed in GC tissues, compared with adjacent normal tissues. The high expression of FGD6 was related to a high histological grade, stage, and T classification and poor prognosis of GC. Multivariate Cox regression analysis showed that FGD6 was an independent prognostic factor for survival of patients with GC. GSEA identified that the high expression of FGD6 was mainly enriched in regulation of actin cytoskeleton. Conclusion: FGD6 may be a prognostic biomarker for predicting the outcome of patients with GC.
Project description:Hepsin, a membrane-associated serine protease, is frequently upregulated in epithelial cancers and involved in cancer progression. Our study aims to describe the expression pattern and evaluate the clinical implication of hepsin in gastric cancer patients. The mRNA expression of hepsin was analyzed in 50 gastric cancer and matched non-tumor tissues, which was downregulated in 78% (39/50) of gastric cancer. By searching and analyzing four independent datasets from Oncomine, we obtained the similar results. Furthermore, we evaluated the hepsin expression by IHC in tissue microarray (TMA) containing 220 Gastric Cancer specimens. More importantly, Kaplan-Meier survival and Cox regression analyses were taken to access the prognosis of gastric cancer and predicted that hepsin protein expression was one of the significant and independent prognostic factors for overall survival of Gastric Cancer.
Project description:The cell surface protein Trop2 is overexpressed in a variety of human cancers. Trop2 expression increases tumor development and metastasis and reduces patient survival. However, little is known about the role of Trop2 expression and its prognostic value in gastric cancer (GC), particularly in Chinese populations. We analyzed Trop2 expression in GC tissues collected from Chinese GC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry on tissue microarrays were performed to assess levels of Trop2 mRNA and protein in GC, and correlations between Trop2 expression and clinical characteristics and prognosis were analyzed. Trop2 expression was higher in GC tissues than in neighboring non-tumor tissues. Increased Trop2 protein levels in GC were associated with increased differentiation, tumor node metastasis stage, tumor size, lymph node metastasis, distant metastasis, and H. pylori infection. GC patients with high Trop2 expression also had poor overall survival rates. These data suggest Trop2 is a useful prognostic biomarker for GC.
Project description:The serine protease inhibitor clade E member 1 (SERPINE1) is a major inhibitor of tissue plasminogen activator and urokinase, and has been implicated in the development and progression of a variety of tumors. In this study, mRNA microarray and TCGA database were used to comprehensively analyze the upregulation of SERPINE1 in gastric cancer (GC) tissues compared with the normal stomach tissues. Kaplan-Meier results confirmed that patients with high SERPINE1 expression exhibited worse overall survival and disease-free survival. In addition, cell proliferation, cell scratches, transwell migration and invasion assay showed that SERPINE1 knockdown inhibited the proliferation, migration and invasion of GC ells. Western blot showed that the expression of VEGF and IL-6 was significantly upregulated after overexpression of SERPINE1. Meanwhile, SERPINE1 was positively correlated with the level of immune infiltration using the online analysis tools TISIDB and TIMER. And SERPINE1 expression increased with the increase of malignancy of GC which were detected by Immunohistochemistry. Finally, tumorigenesis experiments in nude mice further demonstrated that SERPINE1 could promote the occurrence and development of GC, while deletion of SERPINE1 inhibited the progression of GC. In summary, SERPINE1 was highly expressed in GC tissues, and SERPINE1 was helpful for differential diagnosis of pathological grade of gastric mucosal lesions. SERPINE1 might regulate the expression of VEGF and IL-6 through the VEGF signaling pathway and JAK-STAT3 inflammatory signaling pathway, thus ultimately affecting the invasion and migration of GC cells.
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:TP53 gene is often mutated in gastric cancer (GC), nonetheless its relationship with clinicopathological characteristics and prognosis is still unclear. Here, we sought to ascertain the difference in clinical phenotypes between TP53 wild-type and mutant tumors in confirmed gastric cancer patients. To this end, we analyzed TP53 mutation status of 415 TCGA GC patients in relation to their clinical and pathological features as well as prognosis. Longrank Test showed that the survival rate of gastric cancer patients with TP53 WT was significantly lower than that of TP53 mut. Compared with TP53 mut gastric cancer patients with low mRNA expression, TP53 WT patients with low mRNA expression have lower overall survival rate. The death risk of TP53 WT gastric cancer patients is 1.395 times that of TP53 mut gastric cancer patients. The death risk of TP53 mut gastric cancer patients is not related to age, and advanced age is not a risk factor. However, the death risk of TP53 WT patients with gastric cancer increases with age, and the death risk of patients over 70 years old is 1.899 times that of patients under 60 years old. These results suggest that the prognosis of elderly gastric cancer patients with TP53 WT is worse.Conclusionour results indicate that the status of TP53 mutation in GC is significantly correlated with clinical or molecular categories and that the prognosis of GC patients with WT TP53 is worse than that of patients with mutant TP53. Therefore, our data emphasize the importance of distinguishing TP53 WT to predict poor overall survival and relapse-free survival in patients with GC.
Project description:Preoperative pulmonary function assessment is used to select surgical candidates and predict the occurrence of postoperative complications. The present study enrolled 1210 gastric cancer patients (949 males and 261 females). Forced vital capacity (FVC) and maximal voluntary ventilation (MVV) were measured as a percent of predicted values. We then analyzed associations between patient pulmonary function and both prognosis and postoperative complications. Patient 1-, 3- and 5-year overall survival rates were 88.8%, 65.7% and 53.0%, respectively. FVC and MVV optimal cutoff values were 87.0 (P=0.003) and 83.6 (P=0.026), respectively. Low FVC and low MVV were associated with higher rates of postoperative fever (23.8% vs. 13.9%, P<0.001; 17.8% vs. 13.3%, P=0.049, respectively) and poor patient prognosis (5-year overall survival: 43.5% vs. 57.6%, P=0.003; 51.8% vs. 54.3%, P=0.026, respectively). Only low FVC was an independent prognostic predictor for gastric cancer (P=0.012). In subgroup analyses, FVC was not associated with stage I or II gastric cancer patient prognoses (P>0.05), but low FVC was an independent risk factor for poor prognosis in stage III gastric cancer cases (P=0.004). These findings indicate that low FVC is predictive of poorer prognosis and higher risk of postoperative fever in gastric cancer patients.