scholarly journals The Diagnostic and Prognostic Value of BEN-Domain (BEND) Family Genes in Gastric Cancer

Author(s):  
Jiaxin Fan ◽  
Min Yang ◽  
Chaojie Liang ◽  
Chaowei Liang ◽  
Jiansheng Guo

Abstract BEND(BEN domain-containing protein)is a domain protein-coding gene, whose abnormal expression is related to the occurrence of malignant tumors. But studies on gastric cancer are rare. We attempted to investigate the role of BEND family genes in evaluating the prognosis of gastric cancer and guiding clinical treatment. We analyzed the BEND family genes expression, prognostic value, and drug sensitivity in pan-cancer, and the correlation between their expression and tumor microenvironment of gastric cancer, stemness index, immune subtypes, and clinicopathological characteristics were analyzed. We constructed a model using BEND3P1 and BEND6 to evaluate the prognosis of gastric cancer patients. Multivariate Cox proportional risk model analysis showed that risk score is an independent risk factor for gastric cancer patients. To assess the value of risk score for prognosis, patients were divided into high-risk and low-risk groups based on median risk scores, and survival analyses were performed. The results showed that the OS of patients with high-risk scores is significantly lower. We also constructed a nomogram to predict individual survival probability using the BEND risk score and clinical case characteristics. In conclusion, the BEND family genes can predict the prognosis and guide the treatment of gastric cancer patients.

2020 ◽  
Author(s):  
Jieping Qiu ◽  
Mengyu Sun ◽  
Yaoqun Wang ◽  
Bo Chen

Abstract Background: The purpose of this study is to perform bioinformatics analysis of autophagy-related genes in gastric cancer, and to construct a multi-gene joint signature for predicting the prognosis of gastric cancer.Methods: GO and KEGG analysis were applied for differentially expressed autophagy-related genes in gastric cancer, and PPI network was constructed in Cytoscpae software. In order to optimize the prognosis evaluation system of gastric cancer, we established a prognosis model integrating autophagy-related genes. We used single factor Cox proportional risk regression analysis to screen genes related to prognosis from 222 autophagy-related genes in The Atlas Cancer Genome (TCGA) gastric cancer cohort. Then, the generated genes were applied to the Least Absolute Shrinkage and Selection Operator (LASSO). Finally, the selected genes were further included in the multivariate Cox proportional hazard regression analysis to establish the prognosis model. According to the median risk score, patients were divided into high-risk group and low-risk group, and survival analysis was conducted to evaluate the prognostic value of risk score. Finally, by combining clinical features and prognostic gene signatures, a nomogram was established to predict individual survival probability.Results: GO analysis showed that the 38 differently expressed autophagy-related genes was enriched in cell growth, neuron death, and regulation of cell growth. KEGG analysis showed that the 38 differently expressed autophagy-related genes were related to platinum drug resistance, apoptosis and p53 signaling pathway. The risk score was constructed based on 4 genes (GRID2, ATG4D,GABARAPL2, CXCR4), and gastric cancer patients were significantly divided into high-risk and low-risk groups according to overall survival. In multivariate Cox regression analysis, risk score was still an independent prognostic factor (HR = 1.922, 95% CI = 1.573-2.349, P < 0.001). Cumulative curve showed that the survival time of patients with low-risk score was significantly longer than that of patients with high-risk score (P < 0.001). The external data GSE62254 proved that nomograph had a great ability to evaluate the prognosis of individual gastric cancer patients.Conclusions: This study provides a potential prognostic marker for predicting the prognosis of GC patients and the molecular biology of GC autophagy.


2020 ◽  
Author(s):  
Jieping Qiu ◽  
Mengyu Sun ◽  
Yaoqun Wang ◽  
Bo Chen

Abstract Background : The purpose of this study is to perform bioinformatics analysis of autophagy-related genes in gastric cancer, and to construct a multi-gene joint signature for predicting the prognosis of gastric cancer. Methods : GO and KEGG analysis were applied for differentially expressed autophagy-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. In order to optimize the prognosis evaluation system of gastric cancer, we established a prognosis model integrating autophagy-related genes. We used single factor Cox proportional risk regression analysis to screen genes related to prognosis from 204 autophagy-related genes in The Atlas Cancer Genome (TCGA) gastric cancer cohort. Then, the generated genes were applied to the Least Absolute Shrinkage and Selection Operator (LASSO). Finally, the selected genes were further included in the multivariate Cox proportional hazard regression analysis to establish the prognosis model. According to the median risk score, patients were divided into high-risk group and low-risk group, and survival analysis was conducted to evaluate the prognostic value of risk score. Finally, by combining clinic-pathological features and prognostic gene signatures, a nomogram was established to predict individual survival probability. Results : GO analysis showed that the 28 differently expressed autophagy-related genes was enriched in cell growth, neuron death, and regulation of cell growth. KEGG analysis showed that the 28 differently expressed autophagy-related genes were related to platinum drug resistance, apoptosis and p53 signaling pathway. The risk score was constructed based on 4 genes (GRID2, ATG4D,GABARAPL2, CXCR4), and gastric cancer patients were significantly divided into high-risk and low-risk groups according to overall survival. In multivariate Cox regression analysis, risk score was still an independent prognostic factor (HR = 1.922, 95% CI = 1.573-2.349, P < 0.001). Cumulative curve showed that the survival time of patients with low-risk score was significantly longer than that of patients with high-risk score (P < 0.001). The external data GSE62254 proved that nomograph had a great ability to evaluate the prognosis of individual gastric cancer patients. Conclusions: This study provides a potential prognostic marker for predicting the prognosis of GC patients and the molecular biology of GC autophagy.


2020 ◽  
Vol 19 ◽  
pp. 153303382097167
Author(s):  
Tianqi Luo ◽  
Yufei Du ◽  
Jinling Duan ◽  
Chengcai Liang ◽  
Guoming Chen ◽  
...  

Gastric cancer is a malignant tumor with high morbidity and mortality worldwide. However, increasing evidences have revealed the correlation between the glycolysis process and tumorigenesis. This study is aim to develop a list of glycolysis-related genes for risk stratification in gastric cancer patients. We included 500 patients’ sample data from GSE62254 and GSE26942 datasets, and classified patients into training (n = 350) and testing sets (n = 150) at a ratio of 7: 3. Univariate and multivariate Cox regression analysis were performed to screen genes having prognostic value. Based on HALLMARK gene sets, we identified 9 glycolysis-related genes (BPNT1, DCN, FUT8, GMPPA, GPC3, LDHC, ME2, PLOD2, and UGP2). On the basis of risk score developed by the 9 genes, patients were classified into high- and low-risk groups. The survival analysis showed that the high-risk patients had a worse prognosis ( p < 0.001). Similar finding was observed in the testing cohort and 2 independent cohorts (GSE13861 and TCGA-STAD, all p < 0.001). The multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for overall survival ( p < 0.001). Furthermore, we constructed a nomogram that integrated the risk score and tumor stage, age, and adjuvant chemotherapy. Through comparing the results of the receiver operating characteristic curves and decision curve analysis, we found that the nomogram had a superior predictive accuracy than conventional TNM staging system, suggesting that the risk score combined with other clinical factors (age, tumor stage, and adjuvant chemotherapy) can develop a robust prediction for survival and improve the individualized clinical decision making of the patient. In conclusion, we identified 9 glycolysis-related genes from hallmark glycolysis pathway. Based on the 9 genes, gastric cancer patients were separated into different risk groups related to survival.


2009 ◽  
Vol 99 (7) ◽  
pp. 395-401 ◽  
Author(s):  
Jun Chul Park ◽  
Yong Chan Lee ◽  
Jie-Hyun Kim ◽  
Yu Jin Kim ◽  
Sang Kil Lee ◽  
...  

2017 ◽  
Vol 24 (2) ◽  
pp. 393-400 ◽  
Author(s):  
Lorenzo De Franco ◽  
Daniele Marrelli ◽  
Costantino Voglino ◽  
Carla Vindigni ◽  
Francesco Ferrara ◽  
...  

2020 ◽  
Author(s):  
Bin Wu ◽  
Yi Yao ◽  
Yi Dong ◽  
Si Qi Yang ◽  
Deng Jing Zhou ◽  
...  

Abstract Background:We aimed to investigate an immune-related long non-coding RNA (lncRNA) signature that may be exploited as a potential immunotherapy target in colon cancer. Materials and methods: Colon cancer samples from The Cancer Genome Atlas (TCGA) containing available clinical information and complete genomic mRNA expression data were used in our study. We then constructed immune-related lncRNA co-expression networks to identify the most promising immune-related lncRNAs. According to the risk score developed from screened immune-related lncRNAs, the high-risk and low-risk groups were separated on the basis of the median risk score, which served as the cutoff value. An overall survival analysis was then performed to confirm that the risk score developed from screened immune-related lncRNAs could predict colon cancer prognosis. The prediction reliability was further evaluated in the independent prognostic analysis and receiver operating characteristic curve (ROC). A principal component analysis (PCA) and gene set enrichment analysis (GSEA) were performed for functional annotation. Results: Information for a total of 514 patients was included in our study. After multiplex analysis, 12 immune-related lncRNAs were confirmed as a signature to evaluate the risk scores for each patient with cancer. Patients in the low-risk group exhibited a longer overall survival (OS) than those in the high-risk group. Additionally, the risk scores were an independent factor, and the Area Under Curve (AUC) of ROC for accuracy prediction was 0.726. Moreover, the low-risk and high-risk groups displayed different immune statuses based on principal components and gene set enrichment analysis.Conclusions: Our study suggested that the signature consisting of 12 immune-related lncRNAs can provide an accessible approach to measuring the prognosis of colon cancer and may serve as a valuable antitumor immunotherapy.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xin Zhao ◽  
Jiaxuan Zou ◽  
Ziwei Wang ◽  
Ge Li ◽  
Yi Lei

Background. Gastric cancer (GC) is believed to be one of the most common digestive tract malignant tumors. The prognosis of GC remains poor due to its high malignancy, high incidence of metastasis and relapse, and lack of effective treatment. The constant progress in bioinformatics and molecular biology techniques has given rise to the discovery of biomarkers with clinical value to predict the GC patients’ prognosis. However, the use of a single gene biomarker can hardly achieve the satisfactory specificity and sensitivity. Therefore, it is urgent to identify novel genetic markers to forecast the prognosis of patients with GC. Materials and Methods. In our research, data mining was applied to perform expression profile analysis of mRNAs in the 443 GC patients from The Cancer Genome Atlas (TCGA) cohort. Genes associated with the overall survival (OS) of GC were identified using univariate analysis. The prognostic predictive value of the risk factors was determined using the Kaplan-Meier survival analysis and multivariate analysis. The risk scoring system was built in TCGA dataset and validated in an independent Gene Expression Omnibus (GEO) dataset comprising 300 GC patients. Based on the median of the risk score, GC patients were grouped into high-risk and low-risk groups. Results. We identified four genes (GMPPA, GPC3, NUP50, and VCAN) that were significantly correlated with GC patients’ OS. The high-risk group showed poor prognosis, indicating that the risk score was an effective predictor for the prognosis of GC patients. Conclusion. The signature consisting of four glycolysis-related genes could be used to forecast the GC patients’ prognosis.


2021 ◽  
Vol 11 ◽  
Author(s):  
Fen Liu ◽  
Zongcheng Yang ◽  
Lixin Zheng ◽  
Wei Shao ◽  
Xiujie Cui ◽  
...  

BackgroundGastric cancer is a common gastrointestinal malignancy. Since it is often diagnosed in the advanced stage, its mortality rate is high. Traditional therapies (such as continuous chemotherapy) are not satisfactory for advanced gastric cancer, but immunotherapy has shown great therapeutic potential. Gastric cancer has high molecular and phenotypic heterogeneity. New strategies for accurate prognostic evaluation and patient selection for immunotherapy are urgently needed.MethodsWeighted gene coexpression network analysis (WGCNA) was used to identify hub genes related to gastric cancer progression. Based on the hub genes, the samples were divided into two subtypes by consensus clustering analysis. After obtaining the differentially expressed genes between the subtypes, a gastric cancer risk model was constructed through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis. The differences in prognosis, clinical features, tumor microenvironment (TME) components and immune characteristics were compared between subtypes and risk groups, and the connectivity map (CMap) database was applied to identify potential treatments for high-risk patients.ResultsWGCNA and screening revealed nine hub genes closely related to gastric cancer progression. Unsupervised clustering according to hub gene expression grouped gastric cancer patients into two subtypes related to disease progression, and these patients showed significant differences in prognoses, TME immune and stromal scores, and suppressive immune checkpoint expression. Based on the different expression patterns between the subtypes, we constructed a gastric cancer risk model and divided patients into a high-risk group and a low-risk group based on the risk score. High-risk patients had a poorer prognosis, higher TME immune/stromal scores, higher inhibitory immune checkpoint expression, and more immune characteristics suitable for immunotherapy. Multivariate Cox regression analysis including the age, stage and risk score indicated that the risk score can be used as an independent prognostic factor for gastric cancer. On the basis of the risk score, we constructed a nomogram that relatively accurately predicts gastric cancer patient prognoses and screened potential drugs for high-risk patients.ConclusionsOur results suggest that the 7-gene signature related to tumor progression could predict the clinical prognosis and tumor immune characteristics of gastric cancer.


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