KDELR1 Is an Independent Prognostic Predictor and Correlates With Immunity in Glioma

Yuan, Yifan; Yang, Biao; Qi, Zengxin; Han, Zhaolong; Cai, Jiajun; Song, Jianping

doi:10.3389/fonc.2022.783721

Cited by 3 publications

(3 citation statements)

References 42 publications

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“…Additionally, among the genes downregulated with MUC4 expression in GBM, PTPN9 is a tumor suppressor gene in glioma, and its overexpression reduces glioma cell proliferation [107]. Moreover, KDELR1 and LGALS3 overexpression are linked to malignancy and poor prognosis [108][109][110].…”

Section: Discussionmentioning

confidence: 99%

MUC1andMUC4expression are inversely correlated and trigger immunological response and transport pathways in gliomas

Machado,

Ferrer

2024

Preprint

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Diffuse gliomas are tumors that arise from glial or glial progenitor cells. They are currently classified as astrocytoma isocitrate dehydrogenase (IDH)-mutant or oligodendroglioma IDH-mutant, and chromosome arms 1p/19q-codeleted, both slower-growing tumors, or glioblastoma (GBM), a more aggressive tumor. Despite advances in the diagnosis and treatment of gliomas, the median survival time after diagnosis of GBM remains low, approximately 15 months, with a 5-year overall survival rate of only 6.8%. Therefore, new biomarkers and therapy targets that could support better prognosis of these tumors would be of great value. MUC1 and MUC4, membrane-bound mucins, has been identified as a potential biomarker in several tumors. However, the role of these mucins in adult gliomas has not yet been well explored. Here, we show for the first time, in a retrospective study and byin silicoanalysis, the relevance and correlation of these genes in adult gliomas. Analysis of adult diffuse glioma patient cohorts revealed differential methylation and expression patterns of MUC1 and MUC4 across GBM and non-GBM subtypes. GBM patients exhibited decreased MUC1 methylation and elevated expression (r-0.25, p < 0.0001) whereas increased MUC4 methylation and its lower expression (r-0.13, p = 0.1344). Conversely, in non-GBM patients, MUC1 showed higher methylation levels and low expression (r-0.27, p < 0.0001) whereas MUC4 showed lower methylation levels and high expression (r-0.32, p < 0.0001). The expression levels of these genes influenced overall survival (OS) in gliomas patients (p = 0.0344), with high MUC1 and low MUC4 expression associated with worse OS. MUC1 and MUC4 correlated with MUC20 in both GBM (r = 0.54) and non-GBM (r = 0.53) patients (p < 0.0001). Functional enrichment analysis revealed distinct biological roles for co-expressed genes with MUC1 involvement in innate immunity, antigen processing, pro-inflammatory responses in both non-GBM and GBM cohorts, and integrin-based signaling pathways in GBM patients. MUC4 co-expressed genes were involved in ion transport in GBM patients. Using molecular docking, we observed that MUC1 has domains that are physically capable of interacting with immune response-related proteins such as Receptor for Advanced Glycation End-products (RAGE), Major Histocompatibility Complex II (MHCII), and extracellular matrix receptor integrin alpha 2 (ITGA2). These findings shed light on the molecular mechanisms underlying glioma progression and highlight MUC1 and MUC4 as potential prognostic markers and therapeutic targets in glioma management.

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Section: Discussionmentioning

confidence: 99%

MUC1andMUC4expression are inversely correlated and trigger immunological response and transport pathways in gliomas

Machado,

Ferrer

2024

Preprint

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“…COLGALT1 was identi ed as a biomarker for predicting prognosis and immune responses for kidney renal clear cell carcinoma (31). KDELR1 was involved in regulating T cell homeostasis (32) and correlated with the prognosis of glioma (33). MCTS1 was identi ed as an oncogene in various tumors, including HNSC (34), and correlated with immune cell in ltration (35).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-4776-5p acts as a radiosensitizer and predicts the prognosis of patients with head and neck cancer receiving radiotherapy

Lai,

Wang,

et al. 2023

Preprint

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Background Head and neck cancer (HNC) is the most common worldwide. Radiation therapy plays an important role in treating HNC. MicroRNAs (miRNAs) have been associated with tumor progression and radiosensitivity. However, their mechanisms remain largely unknown, and the evidence remains limited. This study aimed to identify miRNAs associated with the radiosensitivity of head and neck tumor cells, leading to the poor prognosis of patients with HNC receiving radiation therapy. The miRNA expression profiles and clinical information of patients with HNC were obtained from The Cancer Genome Atlas. The miRNAs were identified through an integrated bioinformatics analysis and validated through in vitro and in vivo studies. Results MiR-4776-5p was identified as a radiosensitizer and predictor of the prognosis of patients with HNC receiving radiotherapy. Eleven of 16 genes targeted by miR-4776-5p were found to regulate mechanisms related to radiosensitivity via functional annotation. Conclusion In this study, we identified a miRNA, miR-4776-5p, related to the clinical outcome of patients with HNSC receiving RT alone, which could be potentially selected as a miRNA-based therapeutic target to block radioresistant characteristics and lead to better treatment outcomes for HNC.

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“…COLGALT1 has been reported as a biomarker for predicting prognosis and immune responses for kidney renal clear cell carcinoma [31]. KDELR1 involved the regulation of T cell homeostatsis [32] and correlated with the prognosis glioma [33]. MCTS1 has been identified as oncogenes in various tumor entities including HNSC [34] and correlated to immune cell infiltration [35].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-4776-5p acts as a radiosensitizer and predicts the prognosis of patients with head and neck cancer receiving radiotherapy

Lai

Wang

Lin

et al. 2022

Preprint

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Head and neck cancer is the leading cancer worldwide. Radiation therapy plays important role of treatment for head and neck cancer. MicroRNAs have been shown to be related to tumor progression and radiosensitivity. However, the mechanisms are still largely unknown and evidence are still limited. In the current study, we sought to identify the miRNA related the radiosensi-tivity of head and neck tumor cell, which leading to the disappointed prognosis of patients with head and neck cancer receiving radiation therapy. The miRNA expression profiles and clinical information of patients with head and neck cancer were obtained from The Cancer Genome Atlas. The identification of miRNA was carried out through an integrated bioinformatics analysis. The miRNA identified in previous approach was validated through in vitro and in vivo studies. MiR-4776-5p was finally identified as the role of radiosensitizer and predicts the prognosis of patients with head and neck cancer receiving radiotherapy. 11 of 16 genes targeted by the miR-4776-5p have been discovered to regulate the mechanisms related to radiosensitivity using functional annotation.

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KDELR1 Is an Independent Prognostic Predictor and Correlates With Immunity in Glioma

Cited by 3 publications

References 42 publications

MUC1andMUC4expression are inversely correlated and trigger immunological response and transport pathways in gliomas

MUC1andMUC4expression are inversely correlated and trigger immunological response and transport pathways in gliomas

MicroRNA-4776-5p acts as a radiosensitizer and predicts the prognosis of patients with head and neck cancer receiving radiotherapy

MicroRNA-4776-5p acts as a radiosensitizer and predicts the prognosis of patients with head and neck cancer receiving radiotherapy

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