A circadian rhythm-related gene signature associated with tumor immunity, cisplatin efficacy, and prognosis in bladder cancer

Abstract Background: Bladder cancer is one of the most prevalent malignancies worldwide. However, traditional indicators have limited predictive effects on the clinical outcomes of bladder cancer. The aim of this study was to develop and validate a glycolysis-related gene signature for predicting the prognosis of patients with bladder cancer that have limited therapeutic options.Methods: mRNA expression profiling was obtained from patients with bladder cancer from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was conducted to identify glycolytic gene sets that were significantly different between bladder cancer tissues and paired normal tissues. A prognosis-related gene signature was constructed by univariate and multivariate Cox analysis. Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curves were utilized to evaluate the signature. A nomogram combined with the gene signature and clinical parameters was constructed. Correlations between glycolysis-related gene signature and molecular characterization as well as cancer subtypes were analyzed. RT-qPCR was applied to analyze gene expression. Functional experiments were performed to determine the role of PKM2 in the proliferation of bladder cancer cells.Results: Using a Cox proportional regression model, we established that a 4-mRNA signature (NUP205, NUPL2, PFKFB1 and PKM) was significantly associated with prognosis in bladder cancer patients. Based on the signature, patients were split into high and low risk groups, with different prognostic outcomes. The gene signature was an independent prognostic indicator for overall survival. The ability of the 4-mRNA signature to make an accurate prognosis was tested in two other validation datasets. GSEA was performed to explore the 4-mRNA related canonical pathways and biological processes, such as the cell cycle, hypoxia, p53 pathway, and PI3K/AKT/mTOR pathway. A heatmap showing the correlation between risk score and cell cycle signature was generated. RT-qPCR revealed the genes that were differentially expressed between normal and cancer tissues. Experiments showed that PKM2 plays essential roles in cell proliferation and the cell cycle.Conclusion: The established 4‑mRNA signature may act as a promising model for generating accurate prognoses for patients with bladder cancer, but the specific biological mechanism needs further verification.

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A Novel Ferroptosis-related Gene Signature for Overall Survival Prediction in Patients with Bladder cancer

10.21203/rs.3.rs-333257/v1 ◽

2021 ◽

Author(s):

Liyuan Wu ◽

Feiya Yang ◽

Nianzeng Xing

Keyword(s):

Overall Survival ◽

Bladder Cancer ◽

Cox Regression ◽

Risk Group ◽

Risk Groups ◽

Gene Signature ◽

Survival Prediction ◽

Related Gene ◽

Cox Regression Analysis ◽

Prognostic Prediction

Abstract Background Bladder cancer (BC) is a highly heterogeneous disease, which makes the prognostic prediction challenging. Ferroptosis is related to a variety of biological pathways, including those involved in the metabolism of amino acids, lipids, and iron. However, the prognostic value of ferroptosis-related genes in BC remains to be further elucidated. Methods In this study, the mRNA expression profiles and corresponding clinical data of BC patients were downloaded from public databases. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature and validated it. Results Our results showed 12 differentially expressed genes (DEGs) were correlated with overall survival (OS) in the univariate Cox regression analysis (all adjusted P< 0.05). A 9-gene signature was constructed to stratify patients into two risk groups. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group (P < 0.001). The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR> 1, P< 0.01). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups, especially in humoral immune response process. Conclusion In conclusion, a novel ferroptosis-related gene signature can be used for prognostic prediction in BC. Targeting ferroptosis may be a therapeutic alternative for BC.

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An immune cell infiltration-related gene signature predicts prognosis for bladder cancer

Scientific Reports ◽

10.1038/s41598-021-96373-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hualin Chen ◽

Yang Pan ◽

Xiaoxiang Jin ◽

Gang Chen

Keyword(s):

Bladder Cancer ◽

Immune Cells ◽

Immune Cell ◽

External Validation ◽

Gene Signature ◽

Gene Set Enrichment Analysis ◽

Cell Infiltration ◽

Prognostic Indicators ◽

Immune Cell Infiltration ◽

Related Gene

AbstractTo explore novel therapeutic targets, develop a gene signature and construct a prognostic nomogram of bladder cancer (BCa). Transcriptome data and clinical traits of BCa were downloaded from UCSC Xena database and Gene Expression Omnibus (GEO) database. We then used the method of Single sample Gene Set Enrichment analysis (ssGSEA) to calculate the infiltration abundances of 24 immune cells in eligible BCa samples. By weighted correlation network analysis (WGCNA), we identified turquoise module with strong and significant association with the infiltration abundance of immune cells which were associated with overall survival of BCa patients. Subsequently, we developed an immune cell infiltration-related gene signature based on the module genes (MGs) and immune-related genes (IRGs) from the Immunology Database and Analysis Portal (ImmPort). Then, we tested the prognostic power and performance of the signature in both discovery and external validation datasets. A nomogram integrated with signature and clinical features were ultimately constructed and tested. Five prognostic immune cell infiltration-related module genes (PIRMGs), namely FPR1, CIITA, KLRC1, TNFRSF6B, and WFIKKN1, were identified and used for gene signature development. And the signature showed independent and stable prognosis predictive power. Ultimately, a nomogram consisting of signature, age and tumor stage was constructed, and it showed good and stable predictive ability on prognosis. Our prognostic signature and nomogram provided prognostic indicators and potential immunotherapeutic targets for BCa. Further researches are needed to verify the clinical effectiveness of this nomogram and these biomarkers.

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Identification of Metabolic Reprogramming Related Gene Signature to Predict the Prognosis of Bladder Cancer Patients

10.21203/rs.3.rs-132465/v1 ◽

2020 ◽

Author(s):

Tinghao Li ◽

Hang Tong ◽

Hubin Yin ◽

Honghao Cao ◽

Junlong Zhu ◽

...

Keyword(s):

Bladder Cancer ◽

Treatment Options ◽

External Validation ◽

Gene Signature ◽

Gene Expression Omnibus ◽

Metabolic Reprogramming ◽

The Cancer Genome Atlas ◽

Related Gene ◽

Delayed Treatment ◽

Emerging Treatments

Abstract Background: Different kinds of metabolic reprogramming have been widely researched in multifarious cancer types and show up as a guaranteed prognostic predictor, while bladder cancer (BLCA) is most frequent urothelium carcinoma but with poor prognosis despite there are emerging treatments, for lack of reliable predicting biomarkers to early predict the prognosis and delayed treatment options for patients in the terminal stage. Our study aims to explore new prognostic factors related to metabolism in BLCA and make these genes up as novel risk stratification.Methods: We selected a large number of samples downloaded from TCGA (The Cancer Genome Atlas) to find out the possible glycolysis-related genes that correlated with differentiation from cancer sample to normal tissue, aimed to find out a more credible model. To make our signature more believable, we chose the clinical features information from GEO (Gene Expression Omnibus) database as external validation cohort.Results: Finally, we established a three glycolysis-related gene signature based on the expression of AK3, GALK1 and NUP205 to make a prediction on the prognosis of BLCA patients, which were also validated by external cohort and whole mixed cohort. As a result, we built a three glycolysis-related gene signature and found its prognosis value is more valuable in high malignancy patients, which may help physicians to make a more aggressive choice.

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Development of an Aging-Related Gene Signature for Predicting Prognosis, Immunotherapy, and Chemotherapy Benefits in Rectal Cancer

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.775700 ◽

2022 ◽

Vol 8 ◽

Author(s):

Yangyang Wang ◽

Yan Liu ◽

Chunchao Zhu ◽

Xinyu Zhang ◽

Guodong Li

Keyword(s):

Rectal Cancer ◽

Tumor Immunity ◽

Stromal Cell ◽

Cox Regression ◽

Disease Free Survival ◽

Gene Signature ◽

Chemotherapeutic Agents ◽

Related Gene ◽

Data Set ◽

Stromal Activation

Objective: Aging is the major risk factor for human cancers, including rectal cancer. Targeting the aging process provides broad-spectrum protection against cancers. Here, we investigate the clinical implications of aging-related genes in rectal cancer.Methods: Dysregulated aging-related genes were screened in rectal cancer from TCGA project. A LASSO prognostic model was conducted, and the predictive performance was evaluated and externally verified in the GEO data set. Associations of the model with tumor-infiltrating immune cells, immune and stromal score, HLA and immune checkpoints, and response to chemotherapeutic agents were analyzed across rectal cancer. Biological processes underlying the model were investigated through GSVA and GSEA methods. Doxorubicin (DOX)-induced or replicative senescent stromal cells were constructed, and AGTR1 was silenced in HUVECs. After coculture with conditioned medium of HUVECs, rectal cancer cell growth and invasion were investigated.Results: An aging-related model was established, consisting of KL, BRCA1, CLU, and AGTR1, which can stratify high- and low-risk patients in terms of overall survival, disease-free survival, and progression-free interval. ROC and Cox regression analyses confirmed that the model was a robust and independent predictor. Furthermore, it was in relation to tumor immunity and stromal activation as well as predicted the responses to gemcitabine and sunitinib. AGTR1 knockdown ameliorated stromal cell senescence and suppressed senescent stromal cell-triggered rectal cancer progression.Conclusion: Our findings suggest that the aging-related gene signature was in relation to tumor immunity and stromal activation in rectal cancer, which might predict survival outcomes and immuno- and chemotherapy benefits.

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Scoring System Based on RNA Modification Writer-Related Genes to Predict Overall Survival and Therapeutic Response in Bladder Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2021.724541 ◽

2021 ◽

Vol 12 ◽

Author(s):

Pu Zhang ◽

Zijian Liu ◽

Decai Wang ◽

Yunxue Li ◽

Yifei Xing ◽

...

Keyword(s):

Overall Survival ◽

Bladder Cancer ◽

Immune Cell ◽

Cox Regression ◽

Gene Signature ◽

Rna Modification ◽

Lasso Regression ◽

Related Gene ◽

Mutation Burden ◽

Selection Operator

IntroductionIt’s widely reported the “writer” enzymes mediated RNA adenosine modifications which is known as a crucial mechanism of epigenetic regulation in development of tumor and the immunologic response in many kinds of cancers. However, the potential roles of these writer genes in the progression of bladder cancer (BLCA) remain unclear.Materials and MethodsWe comprehensively described the alterations of 26 RNA modification writer genes in BLCA from the genetic and transcriptional fields and identified writer-related genes from four independent datasets. Utilizing least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression, we constructed a ten writer-related gene signature. After that, we confirmed the predictive and prognostic value of this signature on another six independent datasets and established a nomogram to forecast the overall survival (OS) and mortality odds of BLCA patients clinically.ResultsThe writer-related genes signature showed good performance in predicting the OS for BLCA patients. Moreover, the writer-related gene signature was related to EMT-related pathways and immune characteristics. Furthermore, the immune cell infiltration levels of CD8 T cells, cytotoxic cells, M1/2 macrophage cells and tumor mutation burden might be able to predict which patients will benefit from immunotherapy. This could also be reflected by the writer-related gene signature.ConclusionsThis signature might play an important role in precision individualized immunotherapy. The present work highlights the crucial clinical implications of RNA modifications and may help developing individualized therapeutic strategies for patients with BLCA.

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