Comprehensive Analysis of the Clinical and Biological Significances of Endoplasmic Reticulum Stress in Diffuse Gliomas

Huang, Ruoyu; Li, Guanzhang; Wang, Kuanyu; Wang, Zhiliang; Zeng, Fan; Hu, Huimin; Jiang, Tao

doi:10.3389/fcell.2021.619396

Cited by 16 publications

(14 citation statements)

References 64 publications

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“…In Figure 3B , we can find that the curve is the flattest when k = 2 (u1 = 0.2, u2 = 0.8). So, the ideal number of clusters (k = 2) was found using CDF curves and consensus matrices, with patients being divided into two stable clusters ( Huang et al, 2021 ) ( Figure 3B ). Of the 406 BLCA samples, cluster 1 included 333 samples and cluster 2 included 73 samples.…”

Section: Resultsmentioning

confidence: 99%

“…After removing overlapping genes, the obtained ER stress-related gene collection had 272 genes. Among these, 256 genes were discovered in the TCGA dataset ( Huang et al, 2021 ) ( Supplementary Table S1 ), which were screened in this study using differential expression and univariate analysis. The analyses revealed 23 key ER-related genes in BLCA.…”

Section: Resultsmentioning

confidence: 99%

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Prognosis and immune infiltration analysis of endoplasmic reticulum stress-related genes in bladder urothelial carcinoma

2022

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Background: Abnormal activation of endoplasmic reticulum (ER) stress sensors and their downstream signalling pathways is a key regulator of tumour growth, tumour metastasis and the response to chemotherapy, targeted therapy and immunotherapy. However, the study of ER stress on the immune microenvironment of bladder urothelial carcinoma (BLCA) is still insufficient.Methods: Firstly, 23 ER stress genes were selected to analyse their expression differences and prognostic value in BLCA based on the existing BLCA genome atlas data. According to the expression level of ER stress-related genes in BLCA, two independent clusters were identified using consensus cluster analysis. Subsequently, the correlation between these two clusters in terms of the immune microenvironment and their prognostic value was analysed. Finally, we analysed the prognostic value of the key ER stress gene HSP90B1 in BLCA and its corresponding mechanism that affects the immune microenvironment.Results: Consensus clustering showed a worse prognosis and higher expression of immunoassay site-related genes (HAVCR2, PDCD1, CTLA4, CD274, LAG3, TIGIT and PDCD1LG2) in cluster 1 compared with cluster 2. Additionally, both TIMER and CIBERSORT algorithms showed that the expression of immune infiltrating cells in cluster 1 was significantly higher than that in cluster 2. Subsequently, HSP90B1 was identified as a key ER stress gene in BLCA, and its high expression indicated poor prognosis and was closely related to PD1. We also analysed the correlation between HSP90B1 expression and immune-infiltrating cell related biomarkers, which showed positive results. Finally, we verified the prognostic value of HSP90B1 in BLCA using an immunohistochemical assay in a tissue microarray of 100 patients with BLCA, validating the potential of HSP90B1 as a prognostic biomarker in patients with BLCA.Conclusion: Our work reveals that ER stress genes play a crucial role in the BLCA immunological milieu, and HSP90B1 is a potential prognostic biomarker and therapeutic target for cancer immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Prognosis and immune infiltration analysis of endoplasmic reticulum stress-related genes in bladder urothelial carcinoma

2022

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“…Huang et al. ( 18 ) uncovered a ERS-related signature which may serve as a marker for prognosis prediction and individualized therapy of glioma. Zhou et al.…”

Section: Discussionmentioning

confidence: 99%

“…We downloaded the RNA sequencing data, gene mutation data and corresponding clinical information of bladder cancer from TCGA database 1 , and extracted an ERS-related genes from published literature ( 18 ). On the premise that correlation coefficient |R 2 | > 0.3 and p < 0.05 were considered to be statistically significant, we identified ERS-related lncRNAs through Pearson correlation analysis.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of the endoplasmic reticulum stress-related long non-coding RNA in bladder cancer

Wang

Yan

et al. 2022

Front. Oncol.

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BackgroundBladder cancer is ranked the second most frequent tumor among urological malignancies. The research strived to establish a prognostic model based on endoplasmic reticulum stress (ERS)-related long non-coding RNA (lncRNA) in bladder cancer.MethodsWe extracted the ERS-related genes from the published research and bladder cancer data from the Cancer Genome Atlas database. ERS-related lncRNAs with prognostic significance were screened by univariate Cox regression, least absolute shrinkage and selection operator regression analysis and Kaplan-Meier method. Multivariate Cox analysis was leveraged to establish the risk score model. Moreover, an independent dataset, GSE31684, was used to validate the model’s efficacy. The nomogram was constructed based on the risk score and clinical variables. Furthermore, the biological functions, gene mutations, and immune landscape were investigated to uncover the underlying mechanisms of the ERS-related signature. Finally, we employed external datasets (GSE55433 and GSE89006) and qRT-PCR to investigate the expression profile of these lncRNAs in bladder cancer tissues and cells.ResultsSix ERS-related lncRNAs were identified to be closely coupled with patients’ prognosis. On this foundation, a risk score model was created to generate the risk score for each patient. The ERS-related risk score was shown to be an independent prognostic factor. And the results of GSE31684 dataset also supported this conclusion. Then, a nomogram was constructed based on risk scores and clinical characteristics, and proven to have excellent predictive value. Moreover, the gene function analysis demonstrated that ERS-related lncRNAs were closely linked to fatty extracellular matrix, cytokines, cell adhesion, and tumor pathways. Further analysis revealed the association of the 6-lncRNAs signature with gene mutations and immunity in bladder cancer. Finally, the external datasets and qRT-PCR verified high expressions of the ERS-related lncRNAs in bladder cancer tissues and cells.ConclusionsOverall, our findings indicated that ERS-related lncRNAs, which may affect tumor pathogenesis in a number of ways, might be exploited to assess the prognosis of bladder cancer patients.

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“…TIMER2.0 (Tumor Immune Estimation Resource 2.0, , accessed on 1 March 2022) [ 19 , 20 , 21 , 22 ] is a comprehensive resource for the systematic analysis of immune infiltrates across diverse cancer types. In the outcome module, the Cox proportional hazard model covariates were overall survival and FDCSP expression, and the normalized coefficient of the infiltrate for each model across HPV status in HNSC cancer types is presented in a heatmap.…”

Section: Methodsmentioning

confidence: 99%

FDCSP Is an Immune-Associated Prognostic Biomarker in HPV-Positive Head and Neck Squamous Carcinoma

Shao

Huang

et al. 2022

Biomolecules

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Background: Head and neck squamous carcinoma (HNSC) poses a major threat to human life. The role of human papillomavirus (HPV) infection in the initiation and progression of HNSC is becoming more widely accepted. HPV-positive (HPV+) HNSC has shown unique responses to cancer therapies, which may be due to differences in immune cell infiltration. It is critical to determine how the immune responses to HPV in HNSC are regulated. Methods: Transcriptome data of HNSC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database were analyzed. Then, the CIBERSORT algorithm was used to calculate immune cell infiltration in HNSC. FDCSP expression level was detected by qPCR in the HNSC tissues collected from the Nanfang Hospital. Results: Follicular dendritic cell secreted protein (FDCSP) was highly expressed in HPV+ HNSC, and higher expression of FDSCP was associated with a favorable prognosis. In HPV+ HNSC samples, FDCSP significantly increased the proportion of T follicular helper cells (TFHs). FDCSP expression was also found to be associated with TP53 mutation status in HPV+ HNSC. The function of FDCSP was intimately connected to chemokine pathways, particularly with the C-X-C motif chemokine ligand 13 (CXCL13). We verified that the high expression of FDCSP in HPV+ HNSC and higher FDCSP is closely related to prognosis in HNSC samples we collected by qPCR. Conclusions: Collectively, these findings may provide fresh evidence that FDCSP is a potential chemokine-associated prognostic biomarker in HPV+ HNSC.

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Comprehensive Analysis of the Clinical and Biological Significances of Endoplasmic Reticulum Stress in Diffuse Gliomas

Cited by 16 publications

References 64 publications

Prognosis and immune infiltration analysis of endoplasmic reticulum stress-related genes in bladder urothelial carcinoma

Prognosis and immune infiltration analysis of endoplasmic reticulum stress-related genes in bladder urothelial carcinoma

Comprehensive analysis of the endoplasmic reticulum stress-related long non-coding RNA in bladder cancer

FDCSP Is an Immune-Associated Prognostic Biomarker in HPV-Positive Head and Neck Squamous Carcinoma

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