Identification of Candidate Genes Associated With Prognosis in Glioblastoma

Li, Rongjie; Jiang, Qiulan; Tang, Chunhai; Chen, Liechun; Kong, Deyan; Zou, Chun; Lin, Yan; Luo, Jiefeng; Zou, Donghua

doi:10.3389/fnmol.2022.913328

Cited by 7 publications

(6 citation statements)

References 49 publications

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“…More importantly, in terms of clinical value, ANXA2R was only reported to correlate with the prognosis of glioma patients. 55 In our study, ANXA2R showed excellent diagnostic ability for TCMR and AR. The aberrant upregulation of ANXA2R expression indicated the explosion of rejection and significantly worse graft survival for kidney transplant recipients.…”

Section: Discussionsupporting

confidence: 60%

Multiomics Data Reveal the Important Role of ANXA2R in T Cell–mediated Rejection After Renal Transplantation

Zhang,

et al. 2023

Transplantation

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Background. T cell–mediated rejection (TCMR) is a severe issue after renal transplantation, but research on its T cell–receptor (TCR) repertoire is lacking. This study intended to elucidate the TCR repertoire landscape in TCMR and hence identify novel potential targets. Methods. A total of 12 multiomics data sets were collected. The TRUST4 algorithm was used to construct and analyze the TCR repertoire in renal allografts with TCMR and stable renal function. Then, novel TCR-related key genes were identified through various criteria and literature research. In bulk transcriptome, cell line, single-cell transcriptome data sets, multiple immune cell infiltration algorithms, and gene set enrichment analysis were used to analyze potential mechanisms of the identified key gene. Twenty-three pathological sections were collected for immunofluorescence staining in the clinical cohort. Finally, the diagnostic and prognostic values of ANXA2R were evaluated in multiple renal transplant data sets. Results. Allografts with TCMR showed significantly increased clonotype and specific clonal expansion. ANXA2R was found to be a novel key gene for TCMR and showed strong positive connections with the TCR complex and lymphocyte cells, especially CD8+ T cells. Immunofluorescence staining confirmed the existence of ANXA2R+ CD8+ T cells, with their percentage significantly elevated in TCMR compared with stable renal function. Finally, both mRNA and protein levels of ANXA2R showed promising diagnostic and prognostic value for renal transplant recipients. Conclusions. ANXA2R, identified as a novel TCR-related gene, had critical roles in clinicopathology, diagnosis, and prognosis in renal transplantation, which offered promising potential therapeutic targets.

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Section: Discussionsupporting

confidence: 60%

Multiomics Data Reveal the Important Role of ANXA2R in T Cell–mediated Rejection After Renal Transplantation

Zhang,

et al. 2023

Transplantation

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“…For instance, our data identified RPS4X, RPL34, and VMP1 as having more inhibitory effects in ER + BC cells compared to ESR1 inhibition. The RPS4X ribosomal protein has been linked to numerous cancer types, including glioblastoma [ 28 ], lung adenocarcinoma [ 29 ], hepatocellular carcinoma [ 30 ], ovarian cancer [ 31 ], and many others. RPL34 is another ribosomal protein that has been implicated in several cancer types [ 32 , 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptome Analysis Revealed Heterogeneity and Identified Novel Therapeutic Targets for Breast Cancer Subtypes

Vishnubalaji

Alajez

2023

Cells

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Breast cancer (BC) is a heterogeneous disease, which is primarily classified according to hormone receptors and HER2 expression. Despite the many advances in BC diagnosis and management, the identification of novel actionable therapeutic targets expressed by cancerous cells has always been a daunting task due to the large heterogeneity of the disease and the presence of non-cancerous cells (i.e., immune cells and stromal cells) within the tumor microenvironment. In the current study, we employed computational algorithms to decipher the cellular composition of estrogen receptor-positive (ER+), HER2+, ER+HER2+, and triple-negative BC (TNBC) subtypes from a total of 49,899 single cells’ publicly available transcriptomic data derived from 26 BC patients. Restricting the analysis to EPCAM+Lin− tumor epithelial cells, we identified the enriched gene sets in each BC molecular subtype. Integration of single-cell transcriptomic with CRISPR-Cas9 functional screen data identified 13 potential therapeutic targets for ER+, 44 potential therapeutic targets for HER2+, and 29 potential therapeutic targets for TNBC. Interestingly, several of the identified therapeutic targets outperformed the current standard of care for each BC subtype. Given the aggressive nature and lack of targeted therapies for TNBC, elevated expression of ENO1, FDPS, CCT6A, TUBB2A, and PGK1 predicted worse relapse-free survival (RFS) in basal BC (n = 442), while elevated expression of ENO1, FDPS, CCT6A, and PGK1 was observed in the most aggressive BLIS TNBC subtype. Mechanistically, targeted depletion of ENO1 and FDPS halted TNBC cell proliferation, colony formation, and organoid tumor growth under 3-dimensional conditions and increased cell death, suggesting their potential use as novel therapeutic targets for TNBC. Differential expression and gene set enrichment analysis in TNBC revealed enrichment in the cycle and mitosis functional categories in FDPShigh, while ENO1high was associated with numerous functional categories, including cell cycle, glycolysis, and ATP metabolic processes. Taken together, our data are the first to unravel the unique gene signatures and to identify novel dependencies and therapeutic vulnerabilities for each BC molecular subtype, thus setting the foundation for the future development of more effective targeted therapies for BC.

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“…Among them, TMEM60 was the gene with the highest risk score, which belongs to the transmembrane protein family (TMEM), and TMEMs are mostly involved in adverse events related to tumors, such as TMEM88 that leads to proliferation, migration, and invasion of gastric cancer tumors through the JAK2/STAT3 pathway ( 82 ). It has been previously reported that TMEM60 was closely associated with poor prognosis in GBM patients ( 83 ), but no correlation analysis was given, while Yang et al. ( 84 ) also found that high expression of TMEM60 would lead to poor prognosis in GBM patients and hypothesized that it might be related to immunosuppression.…”

Section: Discussionmentioning

confidence: 98%

Unraveling the intricacies of glioblastoma progression and recurrence: insights into the role of NFYB and oxidative phosphorylation at the single-cell level

Liu,

Xing,

Xiahou

et al. 2024

Front. Immunol.

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BackgroundGlioblastoma (GBM), with its high recurrence and mortality rates, makes it the deadliest neurological malignancy. Oxidative phosphorylation is a highly active cellular pathway in GBM, and NFYB is a tumor-associated transcription factor. Both are related to mitochondrial function, but studies on their relationship with GBM at the single-cell level are still scarce.MethodsWe re-analyzed the single-cell profiles of GBM from patients with different subtypes by single-cell transcriptomic analysis and further subdivided the large population of Glioma cells into different subpopulations, explored the interrelationships and active pathways among cell stages and clinical subtypes of the populations, and investigated the relationship between the transcription factor NFYB of the key subpopulations and GBM, searching for the prognostic genes of GBM related to NFYB, and verified by experiments.ResultsGlioma cells and their C5 subpopulation had the highest percentage of G2M staging and rGBM, which we hypothesized might be related to the higher dividing and proliferating ability of both Glioma and C5 subpopulations. Oxidative phosphorylation pathway activity is elevated in both the Glioma and C5 subgroup, and NFYB is a key transcription factor for the C5 subgroup, suggesting its possible involvement in GBM proliferation and recurrence, and its close association with mitochondrial function. We also identified 13 prognostic genes associated with NFYB, of which MEM60 may cause GBM patients to have a poor prognosis by promoting GBM proliferation and drug resistance. Knockdown of the NFYB was found to contribute to the inhibition of proliferation, invasion, and migration of GBM cells.ConclusionThese findings help to elucidate the key mechanisms of mitochondrial function in GBM progression and recurrence, and to establish a new prognostic model and therapeutic target based on NFYB.

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Identification of Candidate Genes Associated With Prognosis in Glioblastoma

Cited by 7 publications

References 49 publications

Multiomics Data Reveal the Important Role of ANXA2R in T Cell–mediated Rejection After Renal Transplantation

Multiomics Data Reveal the Important Role of ANXA2R in T Cell–mediated Rejection After Renal Transplantation

Single-Cell Transcriptome Analysis Revealed Heterogeneity and Identified Novel Therapeutic Targets for Breast Cancer Subtypes

Unraveling the intricacies of glioblastoma progression and recurrence: insights into the role of NFYB and oxidative phosphorylation at the single-cell level

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