Identification of a novel metabolism-related gene signature associated with the survival of bladder cancer

Li, Xiaotao; Shi, Fang; Huang, Yinglong; Luan, Ting; Wang, Haifeng; Wang, Jiansong

doi:10.1186/s12885-021-09006-w

Cited by 11 publications

(5 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Li X et al. identified LRP1 as a metabolism-related gene that is associated with the survival of BLCA ( 29 ), and Xing P et al. revealed that LRP1 was involved in regulating the immune infiltration level in BLCA ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

LDL receptor related protein 1 is an adverse prognostic biomarker that correlates with stromal remodeling and macrophages infiltration in bladder cancer

Liu

Cao

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

IntroductionBladder cancer (BLCA) is a highly heterogeneous disease influenced by the tumor microenvironment, which may affect patients' response to immune checkpoint blockade therapy. Therefore, identifying molecular markers and therapeutic targets to improve treatment is essential. In this study, we aimed to investigate the prognostic significance of LRP1 in BLCA.MethodsWe analyzed TCGA and IMvigor210 cohorts to investigate the relationship of LRP1 with BLCA prognosis. We utilized gene mutation analysis and enrichment to identify LRP1-associated mutated genes and biological processes. Deconvolution algorithms and single-cell analysis were used to understand the tumor-infiltrated cells and biological pathways associated with LRP1 expression. Immunohistochemistry was conducted to validate the bioinformatics analysis.ResultsOur study revealed that LRP1 was an independent risk factor for overall survival in BLCA patients and was associated with clinicopathological features and FGFR3 mutation frequency. Enrichment analysis demonstrated that LRP1 was involved in extracellular matrix remodeling and tumor metabolic processes. Furthermore, the ssGSEA algorithm revealed that LRP1 was positively correlated with the activities of tumor-associated pathways. Our study also found that high LRP1 expression impaired patients' responsiveness to ICB therapy in BLCA, which was predicted by TIDE prediction and validated by IMvigor210 cohort. Immunohistochemistry confirmed the expression of LRP1 in Cancer-Associated Fibroblasts (CAFs) and macrophages in the tumor microenvironment of BLCA.DiscussionOur study suggests that LRP1 may be a potential prognostic biomarker and therapeutic target in BLCA. Further research on LRP1 may improve BLCA precision medicine and enhance the efficacy of immune checkpoint blockade therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

LDL receptor related protein 1 is an adverse prognostic biomarker that correlates with stromal remodeling and macrophages infiltration in bladder cancer

Liu

Cao

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Growing research has shown that lipid metabolic dysregulation is directly related to the emergence of inflammation, cancer, and medication resistance [ 23 ]. Recent research indicates that all metabolic pathways, including those for glucose, amino acids, nucleotides, and other pathways, may function as possible prognostic biomarkers for BLCA [ 24 ], on their molecular-level metabolic control, few investigations have been conducted.…”

Section: Discussionmentioning

confidence: 99%

Prognosis analysis and validation of lipid metabolism-associated lncRNAs and tumor immune microenvironment in bladder cancer

Tan,

Fu,

Zuo

et al. 2023

Aging

Self Cite

View full text Add to dashboard Cite

Background: Numerous types of research revealed that long noncoding RNAs (lncRNAs) played a significant role in immune response and the tumor microenvironment of bladder cancer (BLCA). Dysregulated lipid metabolism is considered to be one of the major risk factors for BLCA, the study aimed to detect the lipid metabolism-related lncRNAs (LMRLs) along with their potential prognostic values and immune correlations in BLCA. Methods: We collected lipid metabolism-related genes, expression profiles, and clinical information on BLCA from the Molecular Signature Database (MSigDB) and the TCGA database, respectively. Differentially expressed lipid metabolism genes (DE-LMRGs) and differentially expressed long non-coding RNAs (DE-lncRNAs) were selected using the limma package. Spearman correlation analysis was employed to explore the correlations between DE-lncRNAs and DE-LMRGs and to further develop protein-protein interaction (PPI) networks and perform mutational analysis. The least absolute shrinkage and selection operator (LASSO) and univariate Cox analysis were then employed to construct a prognostic risk model. The performance of the model was evaluated using Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, and consistency indices. In addition, we downloaded the GSE31684 dataset for external validation of the prognostic signature. Moreover, we explored the association of the risk model with immune cell infiltration and chemotherapy response analysis to reveal the tumor immune microenvironment of BLCA. Finally, RT-qPCR was utilized to validate the expression of prognostic genes. Results: A total of 48 DE-LncRNAs and 33 DE-LMRGs were found to be robustly correlated, and were used to construct a lncRNA-mRNA co-expression network, in which ACACB, ACOX2, and BCHE showed high mutation rates. Then, a risk model based on three LMRLs (RP11-465B22.8, MIR100HG, and LINC00865) was constructed. The risk model effectively distinguished between the clinical outcomes of BLCA patients, with high-risk scores indicating a worse prognosis and with substantial prognostic prediction accuracy. The model's results were consistent in the GSE31684 dataset. In addition, a nomogram was constructed based on the risk score, age, pathological T-stage, and pathological N-stage, which showed robust predictive power. Immune landscape analysis indicated that the risk model was significantly associated with T-cell CD4 memory activation, M1 macrophage, M2 macrophage, dendritic cell activation, and T-cell regulatory. We predicted that 49 drugs would perform satisfactorily in the high-risk group. Additionally, we found five m6A regulators associated with the high- and low-risk groups, suggesting that upstream regulation of LncRNA could be a novel target for BLCA treatment. Finally, RT-qPCR showed that RP11-465B22.8 was highly expressed in BLCA, while MIR100HG and LINC00865 were downregulated in BLCA. Conclusion: Our findings suggest that the three LMRLs may serve as potential prognostic ...

show abstract

“…LRP1, a member of the low density lipoprotein receptor family of proteins encoded by this gene, is involved in a variety of cellular processes, including intracellular signal transduction, lipid homeostasis and the elimination of apoptotic cells [23] . It was included in one of the prognostic evaluation genes of BLCA by many authors [24,25] .…”

Section: Discussionmentioning

confidence: 99%

The Characteristics of Natural Killer Cells and Prediction of Prognosis in Bladder Urothelial Carcinoma

Zhang

Zeng

Song

et al. 2023

Preprint

View full text Add to dashboard Cite

Background：Bladder urothelial carcinoma (BLCA) is a malignant tumor occurring in the bladder and derived from urothelial cells. It is one of the ten most common cancers in the world. There has been no significant progress in the treatment of patients with recurrence of BLCA in the past decades. With the progress of systemic treatment, the overall survival period (OS) of patients has improved, but the prognosis is still poor, which needs improvement clinically. The development of immunotherapy has changed the status initially. Natural killer (NK) cells, as an important type of innate immunomodulatory cells, have proved their potential in the treatment of several malignant tumors, so which received widespread attention in recent years. Objective: The clinical data in TCGA and GEO was used to provide ideas for the diagnosis, treatment and evaluation of prognosis indicators of BLCA. And the relationship between BLCA and the expression of NRGs was investigated. Methods: In this study, the normal and tumor samples of TCGA-BLCA and GSE3167 were analyzed to find out differential expression genes based on the "limma" R package. The genes and the natural killer cell-related genes (NRGs) were intersected to obtain NRGs with differential expression. We used univariate COX regression analysis, LASSO and multifactor COX analysis to obtain the risk score and build the prognosis gene model. GSE31684 queue has been verified externally. In order to further confirm the reliability of genes, we analyzed their mechanism of action, divided them into groups by the risk score, and performed immune analysis on subgroups to evaluate the immune treatment response. Results: There are differences in the expression of LRP1 and INHBB, which are independent risk factors for the prognosis of BLCA. The nomogram was established based on the characteristics of 2-NRGs and clinicopathological characteristics. The low risk group has more abundant immune infiltration, suggesting a better immune response and better prognosis, which verifies the reliability of grouping. The sensitivity of the hig-risk and low-risk group to the two target sites, PDL1 and FGFR3, is significantly different. And the risk score is closely related to the relevant chemotherapy drugs. These suggested that the risk score can screen the patients well at the drug level, and also providing a meaningful reference for the patients in drug selection. Conclusion: NK cell core genes, LRP1 and INHBB, may play a crucial role in the occurrence and progression of BLCA. We constructed nomogram according to the NK core genes and verified its feasibility, which can provide a reference for clinical prognosis.

show abstract

Identification of a novel metabolism-related gene signature associated with the survival of bladder cancer

Cited by 11 publications

References 78 publications

LDL receptor related protein 1 is an adverse prognostic biomarker that correlates with stromal remodeling and macrophages infiltration in bladder cancer

LDL receptor related protein 1 is an adverse prognostic biomarker that correlates with stromal remodeling and macrophages infiltration in bladder cancer

Prognosis analysis and validation of lipid metabolism-associated lncRNAs and tumor immune microenvironment in bladder cancer

The Characteristics of Natural Killer Cells and Prediction of Prognosis in Bladder Urothelial Carcinoma

Contact Info

Product

Resources

About