The correlation of WDR76 expression with survival outcomes and immune infiltrates in lung adenocarcinoma

Fang, Lingling; Yu, Guocan; Yu, Wenfeng; Chen, Gang; Ye, Bo

doi:10.7717/peerj.12277

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…Similar results have also confirmed that WDR76 causes instability of the RAS in CRC, impairing the proliferation and activation of cancer stem cells by inhibiting the Wnt/β-catenin signaling pathway [ 12 ]. Nevertheless, an opposing argument claims that WDR76 specifically acts as an oncogenic factor in lung adenocarcinoma, which is an independent risk factor for prognosis, and that high expression of WDR76 is significantly associated with immune cell infiltration, thereby participating in tumor immunity [ 13 ]. These controversial results illustrate the complexity of WDR76 function in different cancer types.…”

Section: Discussionmentioning

confidence: 99%

WD repeat domain 76 predicts poor prognosis in lower grade glioma and provides an original target for immunotherapy

Cheng,

Liu,

Chang

et al. 2024

Eur J Med Res

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Background The WD40 repeat (WDR) domain provides scaffolds for numerous protein–protein interactions in multiple biological processes. WDR domain 76 (WDR76) has complex functionality owing to its diversified interactions; however, its mechanism in LGG has not yet been reported. Methods Transcriptomic data from public databases were multifariously analyzed to explore the role of WDR76 in LGG pathology and tumor immunity. Laboratory experiments were conducted to confirm these results. Results The results first confirmed that high expression of WDR76 in LGG was not only positively associated with clinical and molecular features of malignant LGG, but also served as an independent prognostic factor that predicted shorter survival in patients with LGG. Furthermore, high expression of WDR76 resulted in the upregulation of oncogenes, such as PRC1 and NUSAP1, and the activation of oncogenic mechanisms, such as the cell cycle and Notch signaling pathway. Finally, WDR76 was shown to be involved in LGG tumor immunity by promoting the infiltration of immune cells, such as M2 macrophages, and the expression of immune checkpoints, such as PDCD1 (encoding PD-1). Conclusions This study shows for the first time the diagnostic and prognostic value of WDR76 in LGG and provides a novel personalized biomarker for future targeted therapy and immunotherapy. Thus, WDR76 may significantly improve the prognosis of patients with LGG.

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Section: Discussionmentioning

confidence: 99%

WD repeat domain 76 predicts poor prognosis in lower grade glioma and provides an original target for immunotherapy

Cheng,

Liu,

Chang

et al. 2024

Eur J Med Res

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“…It has been reported that uncontrollable immune dysfunction promotes the occurrence and development of cancer 29,30 . The inextricable link between lung cancer and immune infiltration has been repeatedly demonstrated 31‐33 . However, the association between immune infiltration and RAGE expression has not been reported.…”

Section: Discussionmentioning

confidence: 99%

“… 29 , 30 The inextricable link between lung cancer and immune infiltration has been repeatedly demonstrated. 31 , 32 , 33 However, the association between immune infiltration and RAGE expression has not been reported. In the present study, GO‐BP enrichment analysis indicated that these co‐expressed genes of RAGE were implicated in the immune‐related pathways, including neutrophil activation involved in immune response, neutrophil degranulation, and regulation of leukocyte‐mediated immunity.…”

Section: Discussionmentioning

confidence: 99%

“…29,30 The inextricable link between lung cancer and immune infiltration has been repeatedly demonstrated. [31][32][33] However, the association between immune infiltration and RAGE expression has not been reported. In the present study, GO-BP enrichment analysis indicated Cellular senescence has been involved in various diseases progression, including tumor, wound healing, and aging.…”

Section: Ta B L E 2 Correlation Analysis Between Rage Expression and ...mentioning

confidence: 99%

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RAGE is a potential biomarker implicated in immune infiltrates and cellular senescence in lung adenocarcinoma

Lin

et al. 2022

Clinical Laboratory Analysis

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Background Receptor for Advanced Glycation End‐products (RAGE) is an oncogene abnormally expressed in various cancers. However, the clinical value of RAGE and the biological role of RAGE in lung cancer have not been fully investigated. Methods We compared the RAGE expression using several public databases. The relationship between RAGE expression and clinicopathological variables was assessed. The R software package was used to carry out enrichment analyses of RAGE co‐expression and gene set enrichment analysis (GSEA). Additionally, we used the TIMER database to assess the association between immune infiltration and RAGE expression. The correlation between RAGE expression and senescence biomarkers in lung adenocarcinoma was analyzed using the TCGA database. Results Our findings indicated that the expression of RAGE was downregulated in lung adenocarcinoma, and down‐regulation of RAGE was related to poor overall survival and disease‐free survival. Functional enrichment analysis indicated that RAGE co‐expression genes were mainly associated with neutrophil activation involved in immune response, neutrophil degranulation, and regulation of leukocyte‐mediated immunity. Correlation analysis revealed that RAGE expression was closely related to the purity of the tumor and immune infiltration. GSEA indicated that the RAGE‐related differential genes were mainly enriched in senescence‐related pathways. Besides, the RAGE expression was significantly associated with senescence‐related genes. Conclusion Down‐regulation of RAGE expression was associated with poor prognosis, as well as defective immune infiltration and cellular senescence in lung adenocarcinoma.

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“…We used nonlinear dimension reduction (t-distributed stochastic neighbour embedding; t-SNE) clustering and the "FindAllMarkers" function (parameters: minimum% = 0:3, log function threshold = 0:25) to identify marker genes based on between-cluster differences. The cell clusters were then annotated based on reported cellspecific marker genes [23][24][25][26][27][28][29].…”

Section: Methodsmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals the Role of Epithelial Cell Marker Genes in Predicting the Prognosis of Colorectal Cancer Patients

2022

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Single-cell RNA sequencing (scRNA-seq) is increasingly used in studies on gastrointestinal cancers. This study investigated the prognostic value of epithelial cell-associated biomarkers in colorectal cancer (CRC) using scRNA-seq data. We downloaded and analysed scRNA-seq data from four CRC samples from the Gene Expression Omnibus (GEO), and we identified marker genes of malignant epithelial cells (MECs) using CRC transcriptome and clinical data downloaded from The Cancer Genome Atlas (TCGA) and GEO as training and validation cohorts, respectively. In the TCGA training cohort, weighted gene correlation network analysis, univariate Cox proportional hazard model (Cox) analysis, and least absolute shrinkage and selection operator regression analysis were performed on the marker genes of MEC subsets to identify a signature of nine prognostic MEC-related genes (MECRGs) and calculate a risk score based on the signature. CRC patients were divided into high- and low-risk groups according to the median risk score. We found that the MECRG risk score was significantly correlated with the clinical features and overall survival of CRC patients, and that CRC patients in the high-risk group showed a significantly shorter survival time. The univariate and multivariate Cox regression analyses showed that the MECRG risk score can serve as an independent prognostic factor for CRC patients. Gene set enrichment analysis revealed that the MECRG signature genes are involved in fatty acid metabolism, p53 signalling, and other pathways. To increase the clinical application value, we constructed a MECRG nomogram by combining the MECRG risk score with other independent prognostic factors. The validity of the nomogram is based on receiver operating characteristics and calibration curves. The MECRG signature and nomogram models were well validated in the GEO dataset. In conclusion, we established an epithelial cell marker gene-based risk assessment model based on scRNA-seq analysis of CRC samples for predicting the prognosis of CRC patients.

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The correlation of WDR76 expression with survival outcomes and immune infiltrates in lung adenocarcinoma

Cited by 6 publications

References 33 publications

WD repeat domain 76 predicts poor prognosis in lower grade glioma and provides an original target for immunotherapy

WD repeat domain 76 predicts poor prognosis in lower grade glioma and provides an original target for immunotherapy

RAGE is a potential biomarker implicated in immune infiltrates and cellular senescence in lung adenocarcinoma

Single-Cell RNA Sequencing Reveals the Role of Epithelial Cell Marker Genes in Predicting the Prognosis of Colorectal Cancer Patients

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