High expression of GPNMB indicates an unfavorable prognosis in glioma: Combination of data from the GEO and CGGA databases and validation in tissue microarray

Xiao, Feng; Zhang, Lina; Ke, Shanbao; Liu, Tao; Hao, Liuwei; Zhao, Pan; Tu, Wenzhi; Cang, Shundong

doi:10.3892/ol.2020.11787

Cited by 16 publications

(12 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We immunostained GPNMB biopsy specimens to investigate the association between OS and PFS, and cases with high GPNMB expression had a very poor prognosis. The same result has been reported for various carcinomas, such as hepatocellular carcinoma (26), epithelial ovarian carcinoma (27), glioma (28), and breast cancer (29); HNSCC was no exception. In renal cell carcinoma, GPNMB expression is closely related to bone metastasis, which is a poor prognostic factor (30); in terms of poor prognostic factors, they are the same as ours.…”

Section: Discussionsupporting

confidence: 86%

GPNMB-Positive Cells in Head and Neck Squamous Cell Carcinoma—Their Roles in Cancer Stemness, Therapy Resistance, and Metastasis

Kawasaki¹,

Suzuki²,

Suzuki³

et al. 2022

Pathol. Oncol. Res.

View full text Add to dashboard Cite

Objective: Despite the use of surgical and chemoradiation therapies, head and neck squamous cell carcinoma (HNSCC) still has a poor prognosis. Immune checkpoint inhibitors have been shown to prolong life expectancy but have limited efficacy. Glycoprotein nonmetastatic melanoma protein B (GPNMB) has received significant attention in breast cancer treatment, in which it has been associated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT); however, the function of GPNMB in HNSCC is completely unknown. This study aimed to clarify the characteristics of GPNMB-positive cells in vitro and their association with the prognosis by immunostaining clinical specimens.Methods: We examined the sphere formation, invasion, and migration ability of GPNMB-positive cells in four HNSCC cell lines in vitro. We also immunostained biopsy specimens with GPNMB from 174 patients with HNSCC diagnosed, treated, and followed-up in our institution to evaluate overall survival and progression-free survival.Results: GPNMB-positive cells showed enhanced sphere formation, invasion, and migration, suggesting that they could have CSC characteristics and the ability to induce EMT, as reported for breast cancer. Clinical specimens showed that overall survival was 39.4% and 57.8% (p = 0.045) and that progression-free survival was 27.6% and 51.6% (p = 0.013) for the high-expression and the low-expression groups, respectively, indicating poor prognosis for the high GPNMB group. The high GPNMB group was also more resistant to chemoradiation and bioradiotherapy. GPNMB was more highly expressed in metastatic lymph nodes than in the primary tumor.Conclusion: GPNMB-positive cells might have CSC characteristics and induce EMT. Detailed functional analyses of GPNMB in HNSCC and the establishment of therapies targeting GPNMB will lead to improved prognoses.

show abstract

Section: Discussionsupporting

confidence: 86%

GPNMB-Positive Cells in Head and Neck Squamous Cell Carcinoma—Their Roles in Cancer Stemness, Therapy Resistance, and Metastasis

Kawasaki¹,

Suzuki²,

Suzuki³

et al. 2022

Pathol. Oncol. Res.

View full text Add to dashboard Cite

show abstract

“…The abnormal expression of many genes is related to the pathological mechanism and malignant progression of glioma (Guan et al, 2018;Wang et al, 2018;Feng et al, 2020;Liu Z. et al, 2020). To determine whether ESPL1 associates with other genes to promote the malignant development of glioma, we further analyzed its co-expression and identified genes with co-expression relationships with ESPL1, confirming ESPL1 as a cancer gene with abnormally high expression that promotes the malignant progression of glioma.…”

Section: Discussionmentioning

confidence: 96%

ESPL1 Is a Novel Prognostic Biomarker Associated With the Malignant Features of Glioma

et al. 2021

View full text Add to dashboard Cite

Research has confirmed that extra spindle pole bodies-like 1 (ESPL1), an etiological factor, promotes the malignant progression of cancers. However, the relationship between ESPL1 and glioma has not yet been demonstrated. The purpose of this study was to reveal the potential mechanisms of ESPL1-mediated malignant glioma progression. Gene expression data and detailed clinical information of glioma cases were obtained from multiple public databases. Subsequently, a series of bioinformatics analyses were used to elucidate the effects of ESPL1 on glioma. The results demonstrated that the mRNA and protein levels of ESPL1 in glioma were higher than those in normal brain tissues. In addition, ESPL1 expression was considerably associated with the clinical and pathological features of gliomas, such as World Health Organization grade, histology, and 1p19q co-deletion status. Importantly, ESPL1 reduced the overall survival (OS) of glioma patients and had prognostic value for gliomas. Gene set enrichment analysis (GSEA) indirectly revealed that ESPL1 regulates the activation of cancer-related pathways, such as the cell cycle and base excision repair pathways. In addition, we used the Connectivity Map (CMap) database to screen three molecular drugs that inhibit ESPL1: thioguanosine, antimycin A, and zidovudine. Finally, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of ESPL1 in glioma cell lines. This study plays an important role in revealing the etiology of glioma by revealing the function of ESPL1, providing a potential molecular marker for the diagnosis and treatment of glioma, especially low-grade glioma.

show abstract

“…Nowadays, lacking of corresponding molecular markers and understanding of the mechanism of glioma pathogenesis bring about a huge challenge to the early diagnosis of glioma [ 8 ]. Although there are some predictive molecular markers such as 1p/19q codeletion and IDH mutations, the high complexity of the molecular mechanism of glioma urgently requires more prognostic markers for glioma [ 9 ]. Therefore, it is imperative to discover new therapeutic strategies to enhance the overall survival of patients with glioma.…”

Section: Introductionmentioning

confidence: 99%

HAUS Augmin-Like Complex Subunit 1 Influences Tumour Microenvironment and Prognostic Outcomes in Glioma

Yao

et al. 2022

Journal of Oncology

View full text Add to dashboard Cite

Background. The expression of HAUS Augmin-like complex subunit 1 (HAUS1), a protein-coding gene, is low in normal samples among various cancers with pan-cancer analysis. The depletion of HAUS1 in cells decreases the G2/M cell compartment and induces apoptosis. However, the detailed expression pattern of HAUS1 and its correlation with immune infiltration in glioma (LGG and GBM) (LGG: low-grade glioma; GBM: glioblastoma) remain unknown. Therefore, in this study, we examined the role and prognostic value of HAUS1 in glioma. Methods. Transcriptional expression data of HAUS1 were collected from the CGGA and TCGA databases. The Kaplan–Meier analysis, univariate and multivariate Cox analyses, and receiver operating characteristic (ROC) curves were used to analyse the clinical significance of HAUS1 in glioma. The STRING database was used to analyse protein-protein interactions (PPI), and the “ClusterProfiler” package was used for functional enrichment analysis to examine the possible biological roles of HAUS1. In addition, the HAUS1 promoter methylation modification was analysed using MEXPRESS, and the association between HAUS1 expression and tumour-infiltrating immune cells was investigated using CIBERSORT. Results. Based on the data retrieved from TCGA (703 samples) and CGGA (1018 samples), an elevated expression of HAUS1 was observed in glioma samples, which was associated with poorer survival of patients, unfavourable clinical characteristics, 1p/19q codeletion status, WHO grade, and IDH mutation status. Furthermore, multivariate and univariate Cox analyses revealed that HAUS1 was an independent predictor of glioma. HAUS1 expression level was associated with several tumour-infiltrating immune cells, such as Th2 cells, macrophages, and activated dendritic cells. The outcomes of ROC curve analysis showed that HAUS1 was good to prognosticate immune infiltrating levels in glioma with a higher area under the curve (AUC) value (AUC = 0.974). Conclusions. HAUS1 was upregulated and served as a biomarker for poor prognosis in patients with glioma. High HAUS1 expression was associated with several tumour-infiltrating immune cells such as Th2 cells, macrophages, and activated dendritic cells, which had high infiltration levels. Therefore, these findings suggest that HAUS1 is a potential biomarker for predicting the prognosis of patients with glioma and plays a pivotal role in immune infiltration in glioma.

show abstract

High expression of GPNMB indicates an unfavorable prognosis in glioma: Combination of data from the GEO and CGGA databases and validation in tissue microarray

Cited by 16 publications

References 60 publications

GPNMB-Positive Cells in Head and Neck Squamous Cell Carcinoma—Their Roles in Cancer Stemness, Therapy Resistance, and Metastasis

GPNMB-Positive Cells in Head and Neck Squamous Cell Carcinoma—Their Roles in Cancer Stemness, Therapy Resistance, and Metastasis

ESPL1 Is a Novel Prognostic Biomarker Associated With the Malignant Features of Glioma

HAUS Augmin-Like Complex Subunit 1 Influences Tumour Microenvironment and Prognostic Outcomes in Glioma

Contact Info

Product

Resources

About