scholarly journals Identifying Novel Cell Glycolysis-Related Gene Signature Predictive of Overall Survival in Gastric Cancer

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.

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Xiaofei Wang ◽  
Jie Qiao ◽  
Rongqi Wang

Abstract The present study aimed to construct a novel signature for indicating the prognostic outcomes of hepatocellular carcinoma (HCC). Gene expression profiles were downloaded from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. The prognosis-related genes with differential expression were identified with weighted gene co-expression network analysis (WGCNA), univariate analysis, the least absolute shrinkage and selection operator (LASSO). With the stepwise regression analysis, a risk score was constructed based on the expression levels of five genes: Risk score = (−0.7736* CCNB2) + (1.0083* DYNC1LI1) + (−0.6755* KIF11) + (0.9588* SPC25) + (1.5237* KIF18A), which can be applied as a signature for predicting the prognosis of HCC patients. The prediction capacity of the risk score for overall survival was validated with both TCGA and ICGC cohorts. The 1-, 3- and 5-year ROC curves were plotted, in which the AUC was 0.842, 0.726 and 0.699 in TCGA cohort and 0.734, 0.691 and 0.700 in ICGC cohort, respectively. Moreover, the expression levels of the five genes were determined in clinical tumor and normal specimens with immunohistochemistry. The novel signature has exhibited good prediction efficacy for the overall survival of HCC patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Xu ◽  
Yida Lu ◽  
Youliang Wu ◽  
Mingliang Wang ◽  
Xiaodong Wang ◽  
...  

Abstract Background Gastric cancer (GC) has a high mortality rate and is one of the most fatal malignant tumours. Male sex has been proven as an independent risk factor for GC. This study aimed to identify immune-related genes (IRGs) associated with the prognosis of male GC. Methods RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs between male GC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analyses were applied to screen survival-associated IRGs. Then, GC patients were separated into high- and low-risk groups based on the median risk score. Furthermore, a nomogram was constructed based on the TCGA dataset. The prognostic value of the risk signature model was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell’s concordance index and calibration curves. In addition, the gene expression dataset from the Gene Expression Omnibus (GEO) was also downloaded for external validation. The relative proportions of 22 types of infiltrating immune cells in each male GC sample were evaluated using CIBERSORT. Results A total of 276 differentially expressed IRGs were screened, including 189 up-regulated and 87 down-regulated genes. Subsequently, a seven-IRGs signature (LCN12, CCL21, RNASE2, CGB5, NRG4, AGTR1 and NPR3) was identified to be significantly associated with the overall survival (OS) of male GC patients. Survival analysis indicated that patients in the high-risk group exhibited a poor clinical outcome. The results of multivariate analysis revealed that the risk score was an independent prognostic factor. The established nomogram could be used to evaluate the prognosis of individual male GC patients. Further analysis showed that the prognostic model had excellent predictive performance in both TCGA and validated cohorts. Besides, the results of tumour-infiltrating immune cell analysis indicated that the seven-IRGs signature could reflect the status of the tumour immune microenvironment. Conclusions Our study developed a novel seven-IRGs risk signature for individualized survival prediction of male GC patients.


2022 ◽  
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.


2021 ◽  
Author(s):  
Xin Xu ◽  
Yida Lu ◽  
Youliang Wu ◽  
Mingliang Wang ◽  
Xiaodong Wang ◽  
...  

Abstract Background: Gastric cancer (GC) has a high mortality rate and is one of the most fatal malignant tumours. Male sex has been proven as an independent risk factor for GC. This study aimed to identify immune-related genes (IRGs) associated with the prognosis of male GC.Method: RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs between male GC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analyses were applied to screen survival-associated IRGs. Then, GC patients were separated into high- and low-risk groups based on the median risk score. Furthermore, a nomogram was constructed based on the TCGA dataset. The prognostic value of the risk signature model was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell’s concordance index and calibration curves. In addition, the gene expression dataset from the Gene Expression Omnibus (GEO) was also downloaded for external validation. The relative proportions of 22 types of infiltrating immune cells in each male GC sample were evaluated using CIBERSORT.Results: A total of 276 differentially expressed IRGs were screened, including 189 up-regulated and 87 down-regulated genes. Subsequently, a seven-IRGs signature (LCN12, CCL21, RNASE2, CGB5, NRG4, AGTR1 and NPR3) was identified to be significantly associated with the overall survival (OS) of male GC patients. Survival analysis indicated that patients in the high-risk group exhibited a poor clinical outcome. The results of multivariate analysis revealed that the risk score was an independent prognostic factor. The established nomogram could be used to evaluate the prognosis of individual male GC patients. Further analysis showed that the prognostic model had excellent predictive performance in both TCGA and validated cohorts. Besides, the results of tumour-infiltrating immune cell analysis indicated that the seven-IRGs signature could reflect the status of the tumour immune microenvironment.Conclusions: Our study developed a novel seven-IRGs risk signature for individualized survival prediction of male GC patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Feng Jiang ◽  
Chuyan Wu ◽  
Ming Wang ◽  
Ke Wei ◽  
Jimei Wang

AbstractOne of the most frequently identified tumors and a contributing cause of death in women is breast cancer (BC). Many biomarkers associated with survival and prognosis were identified in previous studies through database mining. Nevertheless, the predictive capabilities of single-gene biomarkers are not accurate enough. Genetic signatures can be an enhanced prediction method. This research analyzed data from The Cancer Genome Atlas (TCGA) for the detection of a new genetic signature to predict BC prognosis. Profiling of mRNA expression was carried out in samples of patients with TCGA BC (n = 1222). Gene set enrichment research has been undertaken to classify gene sets that vary greatly between BC tissues and normal tissues. Cox models for additive hazards regression were used to classify genes that were strongly linked to overall survival. A subsequent Cox regression multivariate analysis was used to construct a predictive risk parameter model. Kaplan–Meier survival predictions and log-rank validation have been used to verify the value of risk prediction parameters. Seven genes (PGK1, CACNA1H, IL13RA1, SDC1, AK3, NUP43, SDC3) correlated with glycolysis were shown to be strongly linked to overall survival. Depending on the 7-gene-signature, 1222 BC patients were classified into subgroups of high/low-risk. Certain variables have not impaired the prognostic potential of the seven-gene signature. A seven-gene signature correlated with cellular glycolysis was developed to predict the survival of BC patients. The results include insight into cellular glycolysis mechanisms and the detection of patients with poor BC prognosis.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sheng Zheng ◽  
Zizhen Zhang ◽  
Ning Ding ◽  
Jiawei Sun ◽  
Yifeng Lin ◽  
...  

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qian Yan ◽  
Wenjiang Zheng ◽  
Boqing Wang ◽  
Baoqian Ye ◽  
Huiyan Luo ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is a disease with a high incidence and a poor prognosis. Growing amounts of evidence have shown that the immune system plays a critical role in the biological processes of HCC such as progression, recurrence, and metastasis, and some have discussed using it as a weapon against a variety of cancers. However, the impact of immune-related genes (IRGs) on the prognosis of HCC remains unclear. Methods Based on The Cancer Gene Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort) datasets, we integrated the ribonucleic acid (RNA) sequencing profiles of 424 HCC patients with IRGs to calculate immune-related differentially expressed genes (DEGs). Survival analysis was used to establish a prognostic model of survival- and immune-related DEGs. Based on genomic and clinicopathological data, we constructed a nomogram to predict the prognosis of HCC patients. Gene set enrichment analysis further clarified the signalling pathways of the high-risk and low-risk groups constructed based on the IRGs in HCC. Next, we evaluated the correlation between the risk score and the infiltration of immune cells, and finally, we validated the prognostic performance of this model in the GSE14520 dataset. Results A total of 100 immune-related DEGs were significantly associated with the clinical outcomes of patients with HCC. We performed univariate and multivariate least absolute shrinkage and selection operator (Lasso) regression analyses on these genes to construct a prognostic model of seven IRGs (Fatty Acid Binding Protein 6 (FABP6), Microtubule-Associated Protein Tau (MAPT), Baculoviral IAP Repeat Containing 5 (BIRC5), Plexin-A1 (PLXNA1), Secreted Phosphoprotein 1 (SPP1), Stanniocalcin 2 (STC2) and Chondroitin Sulfate Proteoglycan 5 (CSPG5)), which showed better prognostic performance than the tumour/node/metastasis (TNM) staging system. Moreover, we constructed a regulatory network related to transcription factors (TFs) that further unravelled the regulatory mechanisms of these genes. According to the median value of the risk score, the entire TCGA cohort was divided into high-risk and low-risk groups, and the low-risk group had a better overall survival (OS) rate. To predict the OS rate of HCC, we established a gene- and clinical factor-related nomogram. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve showed that this model had moderate accuracy. The correlation analysis between the risk score and the infiltration of six common types of immune cells showed that the model could reflect the state of the immune microenvironment in HCC tumours. Conclusion Our IRG prognostic model was shown to have value in the monitoring, treatment, and prognostic assessment of HCC patients and could be used as a survival prediction tool in the near future.


2018 ◽  
Vol 46 (4) ◽  
pp. 323-329
Author(s):  
E. S. Gershtein ◽  
A. A. Ivannikov ◽  
V. L. Chang ◽  
N. A. Ognerubov ◽  
М. M. Davydov ◽  
...  

Background: Over the last 10 years the incidence of gastric cancer has declined significantly. Nevertheless, it remains one of the most prevalent malignancies both in Russia and worldwide. Therefore, the problems of early diagnostics, prognosis and individualized treatment choice are still on the agenda. Much attention is paid to the evaluation of molecular biological characteristics of the tumor, as well as to the development of multiparametric prognostic systems for gastric cancer based on its identified characteristics. An important place among potential tumor biological markers belongs to matrix metalloproteinases (MMPs) involved into all the stages of tumor progression, first of all, into the regulation of invasion and metastasizing.Aim: Comparative quantitative evaluation of some MMP family members (MMP-2, 7, and 9) and one of the tissue MMP inhibitors (TIMP-2) levels in the tumors and adjacent histologically unchanged mucosa in gastric cancer patients, the analysis of their associations with the main clinical and pathological features of the disease and its prognosis.Materials and methods: Sixty six (66) primary gastric cancer patients (32 male and 34 female) aged 24 to 82 years (median, 61 year) were recruited into the study. Twenty two (22) patients were with stage I of the disease, 11 with stage II, 28 with stage III, and 5 with stage IV. The concentrations of the proteins studied were measured in the tumor and unchanged mucosa extracts by standard direct ELISA kits (Quantikine®, R&D Systems, USA).Results: Tumor MMP-2, 7 and 9 levels were significantly increased, compared to those in the adjacent histologically unchanged mucosa, in 80, 70 and 72% of gastric cancer patients, respectively, while the increase of TIMP-2 level found in 61% of the tumors was not statistically significant. Tumor MMP-2 and TIMP-2 content was increasing significantly with higher T index – size and advancement of the primary tumor (p < 0.01 and p < 0.05 respectively). Tumor MMP-2 level was also increasing in parallel with the N index (regional lymph node involvement; p < 0.01); it was significantly higher in the patients with distant metastases than in those without them (p < 0.05). Tumor MMP-9 and MMP-7 concentrations were not significantly associated with the indices of the tumor progression. The patients were followed up for 1 to 85 months (median, 18.3 months). According to the univariate analysis, high (> 32.6 ng/mg protein) MMP-2 and low MMP-7 (< 1.1 ng/mg protein) levels in the gastric cancer tissue represent statistically significant unfavorable prognostic factors for overall survival. Increased TIMP-2 level is associated with a non-significant decrease in the overall survival (p > 0.05), whereas the MMP-9 level was unrelated to the gastric cancer prognosis. Only T index (p = 0.0034) and tumor MMP-7 content (p = 0.026) remained independent prognostic factors in the multivariate regression analysis.Conclusion: The majority of gastric cancer patients demonstrate a significant increase in the expression of three MMP family members, i.e. gelatinases (MMP-2 and 9), and matrilysin (MMP-7), in the tumors, as compared to adjacent histologically unchanged mucosa. Only MMP-2 levels were associated with the disease progression, increasing with higher TNM system indices. High MMP-2 and low MMP-7 content in the gastric cancer tissue are significant unfavorable prognostic factors for the overall survival in the univariate analysis, but only MMP-7 has retained its independent prognostic value in the multivariate assessment.


2021 ◽  
Vol 11 ◽  
Author(s):  
Meng Cheng ◽  
Libo Sun ◽  
Kebing Huang ◽  
Xiaoyu Yue ◽  
Jie Chen ◽  
...  

Glioma is one of the most common malignant tumors of the central nervous system, and its prognosis is extremely poor. Aberrant methylation of lncRNA promoter region is significantly associated with the prognosis of glioma patients. In this study, we investigated the potential impact of methylation of lncRNA promoter region in glioma patients to establish a signature of nine lncRNA methylated genes for determining glioma patient prognosis. Methylation data and clinical follow-up data were obtained from The Cancer Genome Atlas (TCGA). The multistep screening strategy identified nine lncRNA methylated genes that were significantly associated with the overall survival (OS) of glioma patients. Subsequently, we constructed a risk signature that containing nine lncRNA methylated genes. The risk signature successfully divided the glioma patients into high-risk and low-risk groups. Compared with the low-risk group, the high-risk group had a worse prognosis, higher glioma grade, and older age. Furthermore, we identified two lncRNAs termed PCBP1-AS1 and LINC02875 that may be involved in the malignant progression of glioma cells by using the TCGA database. Loss-of-function assays confirmed that knockdown of PCBP1-AS1 and LINC02875 inhibited the proliferation, migration, and invasion of glioma cells. Therefore, the nine lncRNA methylated genes signature may provide a novel predictor and therapeutic target for glioma patients.


2020 ◽  
Author(s):  
Rui Zhang ◽  
Chen Chen ◽  
Qi Li ◽  
Jialu Fu ◽  
Dong Zhang ◽  
...  

Abstract Background: Immune-related genes (IRGs) play a crucial role in the initiation and progression of cholangiocarcinoma (CCA). However, immune signatures have rarely been used to predict prognosis of CCA. The aim of this study was to construct a novel model for CCA to predict survival based on IRGs expression data.Methods: The gene expression profiles and clinical data of CCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were integrated to establish and validate prognostic IRG signatures. Differentially expressed immune-related genes were screened. Univariate and multivariate Cox analysis were performed to identify prognostic IRGs, and the risk model that predicts outcomes was constructed. Furthermore, receiver operating characteristic (ROC) and Kaplan-Meier curve were plotted to examine predictive accuracy of the model, and a nomogram was constructed based on IRGs signature, combining with other clinical characteristics. Finally, CIBERSORT was used to analyze the association of immune cells infiltration with risk score.Results: We identified that 223 IRGs were significantly dysregulated in patients with CCA, among which five IRGs (AVPR1B, CST4, TDGF1, RAET1E and IL9R) were identified as robust indicators for overall survival (OS), and a prognostic model was built based on the IRGs signature. Meanwhile, patients with high risk had worse OS in training and validation cohort, and the area under the ROC was 0.898 and 0.846, respectively. Nomogram demonstrated that immune risk score contributed much more points than other clinicopathological variables, with a C-index of 0.819 (95% CI, 0.727-0.911). Finally, we found that IRGs signature was positively correlated with the proportion of CD8+ T cells, neurophils and T gamma delta, while negatively with that of CD4+ memory resting T cells.Conclusions: We established and validated an effective five IRGs-based prediction model for CCA, which could accurately classify patients into groups with low and high risk of poor prognosis.


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