scholarly journals Identifying novel cell glycolysis related gene signature predictive of overall survival in bladder urothelial carcinoma

2020 ◽  
Author(s):  
Xin Zhao ◽  
Jia Li ◽  
Jiafeng Li ◽  
Wenjun Xiong ◽  
Rui Jiang
Keyword(s):  
Data Mining ◽  
Overall Survival ◽  
High Risk ◽  
Urothelial Carcinoma ◽  
Risk Group ◽  
Gene Signature ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Related Gene ◽  
Bladder Urothelial Carcinoma

Abstract Background: Bladder urothelial carcinoma (BLCA) is the most common pathological type of bladder cancer and featured by a high risk for relapse and metastasis. Although many biomarkers have been developed by data mining and experimental studies to predict the prognosis of BLCA, a single-gene biomarker usually has poor specificity and sensitivity, leading to unsatisfactory prediction. Therefore, novel gene signatures are needed to more accurately predict the prognosis of BLCA.Methods: Data mining was performed for expression profile analysis of 433 mRNA expression data from the TCGA BLCA patients (n=412). Gene Set Enrichment Analysis (GSEA) was used to interpret the glycolysis-related gene sets. Gene signature related to the prognosis of BLCA was identified by univariate and multivariate Cox regression. A risk score was computed based on three genes by linear regression model and its relation with overall survival was investigated by Kaplan-Meier analysis.Results: Three genes (CHPF, AK3, NUP188) were found to be significantly correlated to the overall survival of BLCA patients. Based on the signature composed of these three genes, 412 BLCA patients were divided into high-risk and low-risk groups. The survival time of the high-risk group was significantly shorter than that of the low-risk group, indicating a worse prognosis.Conclusion: A signature composed of three glycolysis-related genes was developed as biomarkers to predict the prognosis of BLCA and to provide a meaningful reference for the clinical treatment of BLCA.

scholarly journals A Novel Glucose Metabolism-Related Gene Signature for Overall Survival Prediction in Patients with Glioblastoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Chaocai Zhang ◽  
Minjie Wang ◽  
Fenghu Ji ◽  
Yizhong Peng ◽  
Bo Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Glucose Metabolism ◽  
Cox Regression ◽  
Gene Signature ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Survival Prediction ◽  
Related Gene ◽  
Cox Regression Analysis

Introduction. Glioblastoma (GBM) is one of the most frequent primary intracranial malignancies, with limited treatment options and poor overall survival rates. Alternated glucose metabolism is a key metabolic feature of tumour cells, including GBM cells. However, due to high cellular heterogeneity, accurately predicting the prognosis of GBM patients using a single biomarker is difficult. Therefore, identifying a novel glucose metabolism-related biomarker signature is important and may contribute to accurate prognosis prediction for GBM patients. Methods. In this research, we performed gene set enrichment analysis and profiled four glucose metabolism-related gene sets containing 327 genes related to biological processes. Univariate and multivariate Cox regression analyses were specifically completed to identify genes to build a specific risk signature, and we identified ten mRNAs (B4GALT7, CHST12, G6PC2, GALE, IL13RA1, LDHB, SPAG4, STC1, TGFBI, and TPBG) within the Cox proportional hazards regression model for GBM. Results. Depending on this glucose metabolism-related gene signature, we divided patients into high-risk (with poor outcomes) and low-risk (with satisfactory outcomes) subgroups. The results of the multivariate Cox regression analysis demonstrated that the prognostic potential of this ten-gene signature is independent of clinical variables. Furthermore, we used two other GBM databases (Chinese Glioma Genome Atlas (CGGA) and REMBRANDT) to validate this model. In the functional analysis results, the risk signature was associated with almost every step of cancer progression, such as adhesion, proliferation, angiogenesis, drug resistance, and even an immune-suppressed microenvironment. Moreover, we found that IL31RA expression was significantly different between the high-risk and low-risk subgroups. Conclusion. The 10 glucose metabolism-related gene risk signatures could serve as an independent prognostic factor for GBM patients and might be valuable for the clinical management of GBM patients. The differential gene IL31RA may be a potential treatment target in GBM.

scholarly journals Establishment and Validation of a Ferroptosis-Related Gene Signature to Predict Overall Survival in Lung Adenocarcinoma

2022 ◽  
Vol 12 ◽  
Author(s):  
Su Wang ◽  
Zhen Xie ◽  
Zenghong Wu
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Risk Group ◽  
Risk Groups ◽  
Gene Signature ◽  
Low Risk ◽  
Functional Enrichment ◽  
Related Gene ◽  
Prognostic Signature

Background: Lung adenocarcinoma (LUAD) is the most common and lethal subtype of lung cancer. Ferroptosis, an iron-dependent form of regulated cell death, has emerged as a target in cancer therapy. However, the prognostic value of ferroptosis-related genes (FRGs)x in LUAD remains to be explored.Methods: In this study, we used RNA sequencing data and relevant clinical data from The Cancer Genome Atlas (TCGA) dataset and Gene Expression Omnibus (GEO) dataset to construct and validate a prognostic FRG signature for overall survival (OS) in LUAD patients and defined potential biomarkers for ferroptosis-related tumor therapy.Results: A total of 86 differentially expressed FRGs were identified from LUAD tumor tissues versus normal tissues, of which 15 FRGs were significantly associated with OS in the survival analysis. Through the LASSO Cox regression analysis, a prognostic signature including 11 FRGs was established to predict OS in the TCGA tumor cohort. Based on the median value of risk scores calculated according to the signature, patients were divided into high-risk and low-risk groups. Kaplan–Meier analysis indicated that the high-risk group had a poorer OS than the low-risk group. The area under the curve of this signature was 0.74 in the TCGA tumor set, showing good discrimination. In the GEO validation set, the prognostic signature also had good predictive performance. Functional enrichment analysis showed that some immune-associated gene sets were significantly differently enriched in two risk groups.Conclusion: Our study unearthed a novel ferroptosis-related gene signature for predicting the prognosis of LUAD, and the signature may provide useful prognostic biomarkers and potential treatment targets.

Development and validation of a novel ten-gene prognostic signature for hepatocellular carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16665-e16665
Author(s):  
Taicheng Zhou ◽  
Zhihua Cai ◽  
Ning Ma ◽  
Wenzhuan Xie ◽  
Chan Gao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
High Risk Group ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Prognosis Prediction

e16665 Background: Hepatocellular carcinoma (HCC) remains a major challenge for public health worldwide and long-term outcomes remained dismal despite availability of curative treatment. We aimed to construct a multi-gene model for prognosis prediction to inform clinical management of HCC. Methods: RNA-seq data of paired tumor and normal tissue samples of HCC patients from the TCGA and GEO database were used to identify differentially expressed genes (DEGs). DEGs shared by both cohorts along with patients’ survival data of the TCGA cohort were further analyzed using univariate Cox regression and LASSO Cox regression to build a prognostic 10-gene signature, followed by validation of the signature via ICGC cohort and identification of independent prognostic predictors. A nomogram for prognosis prediction was built and Gene Set Enrichment Analysis (GSEA) was performed to further understand the underlying molecular mechanisms. Results: Of 571 patients (70.93% men and 29.07% women; median age [IQR], 65 [56-72] years), a signature of 10 genes was constructed using the training cohort. In the testing and validation cohorts, the signature significantly stratified patients into low- vs high-risk groups in terms of overall survival across and within subpopulations with stage I/II and III/IV disease and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 0.13 [95% CI, 0.07-0.24; P < 0 .001] to 0.38 [95% CI, 0.2-0.71; P < 0.001]) after adjusting for clinicopathological factors. Prognosis was significantly worse in the high-risk group than in the low-risk group across cohorts (P < 0.001 for all). The 10-gene signature achieved a higher accuracy (C-index, 0.84; AUCs for 1-, 3- and 5-year OS, 0.84, 0.81 and 0.85, respectively) than 8 previously reported multigene signatures (C-index range, 0.67 to 0.73; AUCs range, 0.68 to 0.79, 0.68 to 0.80 and 0.67 to 0.78, respectively) for estimation of survival in comparable cohorts. A nomogram incorporating tumor stage and signature-based risk group showed better predictive performance for 1- and 3- year survival than for 5 year survival. Moreover, GSEA revealed that the pathways related to cell cycle regulation were more prominently enriched in the high-risk group while the low-risk group had higher enrichment of metabolic process. Conclusions: Taken together, we established a robust 10-gene signature and a nomogram to predict overall survival of HCC patients, which may help recognize high-risk patients potentially benefiting from more aggressive treatment.

scholarly journals A Novel Autophagy-Related lncRNA Gene Signature to Improve the Prognosis of Patients with Melanoma

2020 ◽  
Author(s):  
Yi Ding ◽  
Tian Li ◽  
Min Li ◽  
Tuersong Tayier ◽  
MeiLin Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Model ◽  
Risk Group ◽  
Clinical Information ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Positive Regulation ◽  
Risk Patients ◽  
Cox Analysis

Abstract Background: Autophagy and long non-coding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma.Methods: We downloaded RNA-sequencing data and clinical information of melanoma from The Cancer Genome Atlas. The co-expression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate COX regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups.Results: According to the results of the univariate COX analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate COX analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group (p<0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism.Conclusion: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNAs risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.

scholarly journals Identification of a Pyroptosis-Related Gene Signature for Predicting Overall Survival and Response to Immunotherapy in Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Susu Zheng ◽  
Xiaoying Xie ◽  
Xinkun Guo ◽  
Yanfang Wu ◽  
Guobin Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Regression Model ◽  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
High Risk Group ◽  
Related Gene

Pyroptosis is a novel kind of cellular necrosis and shown to be involved in cancer progression. However, the diverse expression, prognosis and associations with immune status of pyroptosis-related genes in Hepatocellular carcinoma (HCC) have yet to be analyzed. Herein, the expression profiles and corresponding clinical characteristics of HCC samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then a pyroptosis-related gene signature was built by applying the least absolute shrinkage and selection operator (LASSO) Cox regression model from the TCGA cohort, while the GEO datasets were applied for verification. Twenty-four pyroptosis-related genes were found to be differentially expressed between HCC and normal samples. A five pyroptosis-related gene signature (GSDME, CASP8, SCAF11, NOD2, CASP6) was constructed according to LASSO Cox regression model. Patients in the low-risk group had better survival rates than those in the high-risk group. The risk score was proved to be an independent prognostic factor for overall survival (OS). The risk score correlated with immune infiltrations and immunotherapy responses. GSEA indicated that endocytosis, ubiquitin mediated proteolysis and regulation of autophagy were enriched in the high-risk group, while drug metabolism cytochrome P450 and tryptophan metabolism were enriched in the low-risk group. In conclusion, our pyroptosis-related gene signature can be used for survival prediction and may also predict the response of immunotherapy.

scholarly journals Ferroptosis-related gene signature predicts the prognosis of papillary thyroid carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinyuan Shi ◽  
Pu Wu ◽  
Lei Sheng ◽  
Wei Sun ◽  
Hao Zhang
Keyword(s):  
High Risk ◽  
Immune Cells ◽  
Risk Group ◽  
Gene Signature ◽  
High Risk Group ◽  
Low Risk ◽  
Lasso Regression ◽  
Papillary Thyroid ◽  
Related Gene ◽  
Normal Thyroid

Abstract Background Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC), accounting for more than 80% of all cases. Ferroptosis is a novel iron-dependent and Reactive oxygen species (ROS) reliant type of cell death which is distinct from the apoptosis, necroptosis and pyroptosis. Considerable studies have demonstrated that ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in PTC remains unclear. This study aims at exploring the expression of ferroptosis-related genes (FRG) and their prognostic values in PTC. Methods A ferroptosis-related gene signature was constructed using lasso regression analysis through the PTC datasets of the Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the bioinformatics functions of significantly different genes (SDG) of ferroptosis. Additionally, the correlations of ferroptosis and immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT database. Finally, SDG were test in clinical PTC specimens and normal thyroid tissues. Results LASSO regression model was utilized to establish a novel FRG signature with 10 genes (ANGPTL7, CDKN2A, DPP4, DRD4, ISCU, PGD, SRXN1, TF, TFRC, TXNRD1) to predicts the prognosis of PTC, and the patients were separated into high-risk and low-risk groups by the risk score. The high-risk group had poorer survival than the low-risk group (p < 0.001). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Multivariate regression analysis identified the prognostic signature-based risk score was an independent prognostic indicator for PTC. The functional roles of the DEGs in the TGCA PTC cohort were explored using GO enrichment and KEGG pathway analyses. Immune related analysis demonstrated that the most types of immune cells and immunological function in the high-risk group were significant different with those in the low-risk group. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) verified the SDG have differences in expression between tumor tissue and normal thyroid tissue. In addition, cell experiments were conducted to observe the changes in cell morphology and expression of signature’s genes with the influence of ferroptosis induced by sorafenib. Conclusions We identified differently expressed FRG that may involve in PTC. A ferroptosis-related gene signature has significant values in predicting the patients’ prognoses and targeting ferroptosis may be an alternative for PTC’s therapy.

scholarly journals An autophagy-related long non-coding RNA signature for patients with colorectal cancer

2021 ◽  
Author(s):  
Dongyan Zhao ◽  
Xizhen Sun ◽  
Sidan Long ◽  
Shukun Yao
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
High Risk Group ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Cox Regression Analysis

AbstractAimLong non-coding RNAs (lncRNAs) have been identified to regulate cancers by controlling the process of autophagy and by mediating the post-transcriptional and transcriptional regulation of autophagy-related genes. This study aimed to investigate the potential prognostic role of autophagy-associated lncRNAs in colorectal cancer (CRC) patients.MethodsLncRNA expression profiles and the corresponding clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, autophagy-related lncRNAs were identified by Pearson correlation test. Univariate Cox regression analysis and the least absolute shrinkage and selection operator analysis (LASSO) Cox regression model were performed to construct the prognostic gene signature. Gene set enrichment analysis (GSEA) was used to further clarify the underlying molecular mechanisms.ResultsWe obtained 210 autophagy-related genes from the whole dataset and found 1187 lncRNAs that were correlated with the autophagy-related genes. Using Univariate and LASSO Cox regression analyses, eight lncRNAs were screened to establish an eight-lncRNA signature, based on which patients were divided into the low-risk and high-risk group. Patients’ overall survival was found to be significantly worse in the high-risk group compared to that in the low-risk group (log-rank p = 2.731E-06). ROC analysis showed that this signature had better prognostic accuracy than TNM stage, as indicated by the area under the curve. Furthermore, GSEA demonstrated that this signature was involved in many cancer-related pathways, including TGF-β, p53, mTOR and WNT signaling pathway.ConclusionsOur study constructed a novel signature from eight autophagy-related lncRNAs to predict the overall survival of CRC, which could assistant clinicians in making individualized treatment.

scholarly journals The m6A-related gene signature for predicting the prognosis of breast cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11561
Author(s):  
Shanliang Zhong ◽  
Zhenzhong Lin ◽  
Huanwen Chen ◽  
Ling Mao ◽  
Jifeng Feng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Cancer Survival ◽  
Risk Group ◽  
Gene Signature ◽  
Breast Cancer Survival ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Rna Methylation

N6-methyladenosine (m6A) modification has been shown to participate in tumorigenesis and metastasis of human cancers. The present study aimed to investigate the roles of m6A RNA methylation regulators in breast cancer. We used LASSO regression to identify m6A-related gene signature predicting breast cancer survival with the datasets downloaded from Gene Expression Omnibus and The Cancer Genome Atlas (TCGA). RNA-Seq data of 3409 breast cancer patients from GSE96058 and 1097 from TCGA were used in present study. A 10 m6A-related gene signature associated with prognosis was identified from 22 m6A RNA methylation regulators. The signature divided patients into low- and high-risk group. High-risk patients had a worse prognosis than the low-risk group. Further analyses indicated that IGF2BP1 may be a key m6A RNA methylation regulator in breast cancer. Survival analysis showed that IGF2BP1 is an independent prognostic factor of breast cancer, and higher expression level of IGF2BP1 is associated with shorter overall survival of breast cancer patients. In conclusion, we identified a 10 m6A-related gene signature associated with overall survival of breast cancer. IGF2BP1 may be a key m6A RNA methylation regulator in breast cancer.

scholarly journals A glycolysis-related gene expression signature in predicting recurrence of breast cancer

2020 ◽  
Author(s):  
Jianing Tang ◽  
Gaosong Wu
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Group ◽  
Gene Signature ◽  
Low Risk ◽  
Individual Treatment ◽  
Breast Cancer Patients ◽  
Related Gene

Abstract Background Metabolic change is the hallmark of cancer. Even in the presence of oxygen, cancer cells reprogram their glucose metabolism to enhance glycolysis and reduce oxidative phosphorylation. In the present study, we aimed to develop a glycolysis-related gene signature to predict the prognosis of breast cancer patients.Methods Gene expression profiles and clinical data of breast cancer patients were obtained from the GEO database. Univariate, Lasso-penalized, and multivariate Cox analysis were performed to construct the glycolysis-related gene signature.Results A four-gene based signature (ALDH2, PRKACB, STMN1 and ZNF292) was developed to separate patients into high-risk and low-risk groups. Kaplan-Meier survival analysis demonstrated that patients in low-risk group had significantly better prognosis than those in the high-risk group. Time-dependent ROC analysis demonstrated that the glycolysis-related gene signature had excellent prognostic accuracy. We further confirmed the expression of the four prognostic genes in breast cancer and paracancerous tissues samples using qRT-PCR analysis. Expression level of PRKACB was higher in paracancerous tissues, while STMN1 and ZNF292 were overexpressed in tumor samples. No difference was found in ALDH2 expression. The same results were observed in the IHC data from the human protein atlas. Global proteome data of 105 TCGA breast cancer samples obtained from the Clinical Proteomic Tumor Analysis Consortium were used to evaluate the prognostic value of their protein levels. Consistently, high expression of PRKACB protein level was associated with better prognosis, while high ZNF292 and STMN1 protein expression levels indicated poor prognosis.Conclusions The glycolysis-related gene signature might provide an effective prognostic predictor and a new view for individual treatment of breast cancer patients.

An Immune-Related Gene Pairs Signature Predicts Overall Survival in Melanoma

2021 ◽  
Author(s):  
Ding Pan ◽  
Qi-Feng Ou ◽  
Pan-Feng Wu ◽  
Fang Yu ◽  
Ju-Yu Tang
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Related Gene ◽  
Immune Genes ◽  
Gene Pairs ◽  
Immune Related Gene ◽  
Public Data

Abstract Background:The incidence rate and mortality rate of melanoma have been increasing in recent decades. Increasing evidence has depicted the correlation between melanoma prognosis and immune signature. Therefore, the aim of this study is to develop a robust prognostic immune-related gene pairs (IRGPs) signature for estimating overall survival (OS) of melanoma.Methods:Gene expression profiling and clinical information of melanoma patients were derived from two public data sets, divided into training and validation cohorts. Immune genes significantly associated with prognosis were selected. Results:Among 1,646 immune genes, a 25 IRGPs signature was built which was significantly associated with OS in the training cohort (P=1.80×10−22; hazard ratio [HR] =9.50 [6.04, 14.93]). In the validation datasets, the IRGPs signature significantly divided patients into high- vs low- risk groups considering their prognosis (P=2.47×10−4; HR =2.99 [1.66, 5.38]) and was prognostic in multivariate analysis. Functional analysis showed that several biological processes, including keratinization and pigment phenotype-related pathways, enriched in the high-risk group. Macrophages M0, NK cells resting and T cells gamma delta were significantly higher in the high-risk group compared with the low-risk group. Conclusions:We successfully constructed a robust IRGPs signature with prognostic values for melanoma, providing new insights into post-operational treatment strategies.

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