Poor Prognosis In Glioma Research Articles

Expression and Prognostic Value of ARID5A and its Correlation With Tumor-Infiltrating Immune Cells in Glioma.

AT-rich interaction domain 5A (ARID5A) is a member of the ARID family with a function that has been linked to autoimmune as well as inflammatory diseases. Some ARID family members are involved in the initiation and progression of human cancers. However, the function of ARID5A in glioma remains unknown. In this study, ARID5A expression levels were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database. Subsequently, the relationship between ARID5A expression and the clinical characteristics of glioma patients was evaluated using the Chinese Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) database. The prognostic value of ARID5A in glioma was estimated by Kaplan-Meier analysis and the receiver operating characteristic (ROC) curve analysis. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were performed for functional prediction. The Tumor Immune Estimation Resource (TIMER) database was used to analyze the relationship between ARID5A and immune cell infiltration in glioma. Our results demonstrate that the expression of ARID5A was upregulated in glioma compared with that in nontumor brain tissues. High expression of ARID5A is associated with poor prognosis in glioma. We found that the expression of ARID5A was significantly upregulated with an increase in tumor malignancy. GO analysis revealed that co-expression genes of ARID5A are significantly involved in some important functions in glioma, and GSEA showed that multiple cancer-associated and immune-associated signaling pathways are enriched in the high ARID5A expression group. TIMER database indicated that ARID5A is correlated with tumor-infiltrating immune cells in glioma. Collectively, these findings indicate that ARID5A may be a potential prognostic biomarker and is correlated with immune infiltration in glioma.

Effects of SV2B on proliferation, invasion and migration of human glioma cells

Objective To study the effects of synaptic vesicle glycoprotein 2B（SV2B） on proliferation, invasion and migration of human glioma cells. Methods Bioinformatics analysis of the prognosis of malignant glioma related genes, and to establish a stable expression SV2B cell line U251 and U87, using the fluorescence microscope and image cells infected with fluorescence efficiency, further extraction cell protein and Westblot experiment, testing each SV2B protein expression, scratch test each cell migration ability, Transwell migration experiment testing each cell migration ability, Transwell invasion experiment testing each cell invasive, EdU experiment testing each cell proliferation, The cell proliferation ability was detected by plate colony formation assay. Results Bioinformatics analysis showed that SV2B was a gene associated with poor prognosis in glioma, and high expression of SV2B protein was associated with shorter survival time in GBM patients. In the stably expressing SV2B cell lines constructed by lentivirus, overexpression of SV2B family caused the enhancement of proliferation, invasion and migration of human glioma cells. Conclusion SV2B plays an important role in proliferation, invasion and migration of human glioma cells.

Nitidine chloride suppresses epithelial-mesenchymal transition and stem cell-like properties in glioblastoma by regulating JAK2/STAT3 signaling.

Glioblastoma is the most aggressive and common intracranial malignant tumor, and the prognosis is still poor after various treatments. Based on the poor prognosis of glioma, new drugs that suppress the rapid progression and aggressive growth of glioma are urgently needed. It has been reported that nitidine chloride (NC) can inhibit tumor growth and epithelial‐mesenchymal transition (EMT), and EMT is associated with cancer stem cell properties. The present study aimed to investigate the inhibitory effect of NC on the EMT process and stem cell‐like properties in glioma cells. The results showed that the migration and invasion abilities in U87 and LN18 glioma cells were significantly increased after the induction of EMT and these effects were inhibited by NC in a concentration‐dependent manner. NC treatment decreased the expression of EMT markers in glioma cells and self‐renewal capacity of glioma stem‐like cells. We demonstrated that these effects of NC were achieved via JAK2/STAT3 signaling. Taken together, these results indicate that NC inhibits the EMT process and glioma stem‐like properties via JAK2/STAT3 signaling pathway, suggesting that NC may be a potential anti‐glioma drug.

Overexpression of microRNA-939-5p Contributes to Cell Proliferation and Associates Poor Prognosis in Glioma.

Glioma is the main brain tumor worldwide and has a worse prognosis. MicroRNAs (miRNAs) are proved to involve in massive malignant tumors including glioma. In this study, we tried to detect the microRNA-939-5p (miR-939-5p) expression pattern and explore its prognostic significance in glioma. We performed the quantitative real-time PCR to examine the relative expression of miR-939-5p in glioma. The Kaplan-Meier method and Cox regression analysis were used to reveal the prognostic importance of miR-939-5p. The influence of miR-939-5p on cell proliferation, migration, and invasion was investigated by the Cell Counting kit-8 (CCK-8), colony formation assay, and Transwell assay. Besides, the target gene of miR-939-5p was provided by luciferase reporter assay. Our data substantiated the expression of miR-939-5p was obviously increased in glioma tissues and cell lines. The upregulation of miR-939-5p predicted a poor survival rate and might act as an alternative prognostic indicator in glioma. The elevated expression of miR-939-5p boosted proliferation, migration, and invasion in glioma cell lines. The alternation of miR-939-5p changed the protein expression of TIMP metallopeptidase inhibitor 2 (TIMP2). These findings indicated the overexpression of miR-939-5p was associated with the poor prognosis of glioma patients. MiR-939-5p may function as an oncogene by targeting TIMP2.

LncRNA MIR503HG inhibits cell proliferation and promotes apoptosis in TNBC cells via the miR-224-5p/HOXA9 axis

Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer. This study investigated the molecular mechanism and influences of MIR503HG, miR-224-5p, and homeobox A9 (HOXA9) on TNBC cell growth and migration. Dual-luciferase reporter gene and RNA immunoprecipitation were performed to examine the regulation of MIR503HG, miR-224-5p, and HOXA9. Cell proliferation, apoptosis, migration, and invasion were evaluated by colony formation, flow cytometry, and Transwell assays. Finally, nude mice were employed to investigate the influence of MIR503HG on TNBC tumor growth. HOXA9 protein levels were detected by immunohistochemical staining. MIR503HG and HOXA9 expression were reduced in TNBC, while miR-224-5p was increased. Overexpression of MIR503HG or HOXA9 reduced the cell migration ability and proliferation and promoted apoptosis, and knockdown of MIR503HG or overexpression of miR-224-5p exhibited the opposite effects. Furthermore, MIR503HG promoted HOXA9 expression by inhibiting miR-224-5p. Overexpression of miR-224-5p reversed the effects of MIR503HG overexpression on TNBC cells, while overexpression of HOXA9 reversed the effect of MIR503HG knockdown. Additionally, an in vivo study proved that MIR503HG inhibited TNBC tumor growth via the miR-224-5p/HOXA9 axis. MIR503HG inhibited cell proliferation and promoted the apoptosis of TNBC cells via the miR-224-5p/HOXA9 axis, which may function as a novel target for the treatment of TNBC.

ELF1 Transcription Factor Enhances the Progression of Glioma via ATF5 promoter.

A key transcriptional activator, activating transcription factor 5 (ATF5), is aberrantly overexpressed in glioma and supports both poor prognosis and antiapototic potential. Unfortunately, data on ATF5 is largely based on its regulatory mechanism. Further investigation of the upstream regulatory factor for ATF5 transcription in glioma is required. Clinical data for patients with diagnosed glioma were obtained from The Cancer Genome Atlas (TCGA). Additionally, transcription factors potentially regulating the ATF5 promoter in glioma were screened with bioinformatics. A further experimental study was performed to investigate both the role of E74-like factor 1 (ELF1) and the binding of ELF1 and the ATF5 promoter in glioma. We show that ATF5 expression is upregulated in glioma tissues and associated with tumor malignancy and worse prognosis. As a putative upstream regulator, silencing ELF1 inhibits glioma cell growth and migration with ATF5 involvement. Moreover, ELF1 upregulation is also associated with poor prognosis in glioma. Importantly, the luciferase assay and chromatin immunoprecipitation (ChIP) reveal that the ATF5 gene promoter is essential for ELF1-dependent activation of ATF5 gene transcription. These results indicate that a high expression of ELF1 may be related to the malignant behavior of human glioma and ELF1 promotes glioma development mediated by transactivation of the ATF5 gene.

PDIA5 is Correlated With Immune Infiltration and Predicts Poor Prognosis in Gliomas.

Gliomas are the most common and lethal primary malignant tumor of the brain. Routine treatment including surgical resection, chemotherapy, and radiotherapy produced limited therapeutic effect, while immunotherapy targeting the glioma microenvironment has offered a novel therapeutic option. PDIA5 protein is the member of PDI family, which is highly expressed in glioma and participates in glioma progression. Based on large-scale bioinformatics analysis, we discovered that PDIA5 expression level is upregulated in aggressive gliomas, with high PDIA5 expression predicting poor clinical outcomes. We also observed positive correlation between PDIA5 and immune infiltrating cells, immune related pathways, inflammatory activities, and other immune checkpoint members. Patients with high PDIA5 high-expression benefited from immunotherapies. Additionally, immunohistochemistry revealed that PDIA5 and macrophage biomarker CD68 were upregulated in high-grade gliomas, and patients with low PDIA5 level experienced favorable outcomes among 33 glioma patients. Single cell RNA sequencing exhibited that PDIA5 was in high level presenting in neoplastic cells and macrophages. Cell transfection and co-culture of glioma cells and macrophages revealed that PDIA5 in tumor cells mediated macrophages exhausting. Altogether, our findings indicate that PDIA5 overexpression is associated with immune infiltration in gliomas, and may be a promising therapeutic target for glioma immunotherapy.

Germline ALK variations are associated with a poor prognosis in glioma and IDH-wildtype glioblastoma.

Glioma is the most common primary brain tumor. Clear classification is crucial for accurate diagnosis and individualized treatment. Histopathological characteristics and genetic alterations have shown to be related to prognosis and treatment response. Germline variants are important components of genetic alterations. However, the distribution of germline variations in glioma patients and their association with survival remain unknown. We carried out whole-exome sequencing on 99 cases to explore germline variants in glioma. We also analyzed the association of germline variants with clinicopathological features and other prognostic indicators. All the glioma cases harbored rare germline variants. Germline ALK variants (gALK-Mut) were identified in 12/99 (12.12%) patients. The gALK-Mut patients had significantly shorter overall survival than germline ALK wildtype (gALK-WT) patients in the all glioma group (99 cases) and the subset of patients with IDH-wildtype glioblastoma (IDH-WT-GBM, 39 cases) (P = 0.013 and 0.027, respectively). The gALK-Mut patients also had higher frequency of BIRC5, PIK3CA and RPN1 somatic mutations than the gALK-WT patients in IDH-WT-GBM. Other confounding factors appeared to contribute to patient survival. The subgroup of patients in IDH-WT-GBM with gALK-Mut/TP53-Mut had worse prognosis than the gALK-WT/TP53-Mut subgroup (P = 0.031); The gALK-Mut/TERT-WT and gALK-Mut/TERT-Mut subgroups both had a worse prognosis than the gALK-WT/TERT-Mut subgroup (P = 0.031 and 0.018, respectively). Our study revealed ALK variation was an independent indicator of poor prognosis in glioma and IDH-WT-GBM. It could be a promising biomarker and tractable therapeutic target for this deadly disease.

Knocking down of Polo-like kinase 2 inhibits cell proliferation and induced cell apoptosis in human glioma cells

AimsPolo-like kinase 2 (PLK2) belongs to a family of serine/threonine kinases, and it is involved in tumorigenesis. The present study aimed to explore the potential clinical significance of PLK2 in the development of gliomas. Main methodsImmunohistochemistry (IHC) was performed to detect the expression of PLK2 in glioma tissues. Cell proliferation and apoptosis were determined by Cell Counting Kit 8 (CCK8) and flow cytometry analysis, respectively. Key findingsPLK2 expression gradually increased with the degree of glioma malignancy. High PLK2 expression was associated with a poor prognosis in glioma. Short hairpin RNAs targeting PLK2 (shPLK2) inhibited the viability and induced apoptosis of glioma cells, both in vitro and in vivo. Ring finger protein 180 (RNF180), an E3 ubiquitin ligase, interacted with PLK2 and induced the ubiquitination of PLK2. Overexpression of PLK2 in glioma cells significantly inhibited RNF180 upregulation-induced cell apoptosis. The expression level of RNF180 gradually decreased with the degree of glioma malignancy. SignificanceKnocking down of PLK2 may suppress the glioma development through cancer cell proliferation inhibition and cell apoptosis promotion. Furthermore, RNF180 may mediate the ubiquitination of PLK2. The present findings may help improve the clinical management of glioma in the future.

Identification of Glioma Specific Genes as Diagnostic and Prognostic Markers for Glioma

Background: Malignant gliomas are the most prevalent malignancy of the brain. However, there was still lack of sensitive and accurate biomarkers for gliomas. Objective: To explore the mechanisms underlying glioma progression and identify novel diagnostic and prognostic markers for glioma. Methods: By analyzing TCGA dataset, whole-genome genes expression levels were evaluated in 19 different types of human cancers. A protein-protein interacting network was constructed to reveal the potential roles of these glioma special genes. KEGG and GO analysis revealed the potential effect of these genes. Results: We identified 698 gliomas specially expressed genes by analyzing TCGA dataset. A protein-protein interacting network was constructed to reveal the potential roles of these glioma special genes. KEGG and GO analysis showed gliomas specially expressed genes were involved in regulating neuroactive ligand-receptor interaction, retrograde endocannabinoid signaling, Glutamatergic synapse, chemical synaptic transmission, nervous system development, central nervous system development, and learning. Of note, GRIA1, GNAO1, GRIN1, CACNA1A, CAMK2A, and SYP were identified to be down-regulated and associated with poor prognosis in gliomas. Conclusion: GRIA1, GNAO1, GRIN1, CACNA1A, CAMK2A, and SYP were identified to be down-regulated and associated with poor prognosis in gliomas. We thought this study will provide novel biomarkers for gliomas.

High expression of cluster of differentiation 276 indicates poor prognosis in glioma.

Background:Glioma is the central nervous system tumor with the highest incidence rate and the molecular detection of gliomas has been the focus of research. This study aimed to investigate the guiding effect of cluster of differentiation 276 (CD276) expression on the clinical prognosis of glioma.Methods:The TCGA and CGGA databases were used to study whether CD 276 can be used as an independent prognostic factor for gliomas. Immunohistochemistry was used to detect the expression of CD276, isocitrate dehydrogenase-1 (IDH1), matrix metallopeptidase 9 (MMP9), p53, and Ki-67, and 1p/19q co-deletion was detected by fluorescence in situ hybridization (FISH). The effects of CD276 RNA interference (RNAi) on cell invasion, cell cycle and the expression of β-catenin, tumor necrosis factor receptor 1 (TNFR1), and MMP9 were observed. Furthermore, the biological effects of CD276 gene knockout on intracranial transplanted tumors in nude mice were studied.Results:CD276 expression was positively correlated with the extracellular matrix, collagen decomposition, and cell adhesion molecules. Immunohistochemistry and FISH showed that CD276 expression positively correlated with the glioma grade, p53 mutation, Ki-67 proliferation, and MMP9 expression; however, it negatively correlated with IDH1 mutation, 1p/19q co-deletion, and the survival rate. CD276 RNAi in U87 cells inhibited cell proliferation, migration, and invasion, but had no effect on the cell cycle. CD276 inhibited the expression of β-catenin, TNFR1, and MMP9 in U87 cells at the mRNA and protein levels. In vivo experiments showed that the tumor formation and invasion of the CD276 small interfering RNA glioma cell line in nude mice were reduced and the survival time was prolonged.Conclusions:The present study demonstrated that high expression of CD276 in gliomas indicates a poor prognosis.

Downregulation of Brain Enriched Type 2 MAGEs Is Associated With Immune Infiltration and Poor Prognosis in Glioma.

Melanoma associated antigen (MAGE) is an extensively studied family of tumor-associated genes that share a common MAGE homology domain (MHD). Based upon their expression pattern, MAGE genes have been broadly classified into type 1 MAGEs (T1Ms) and type 2 MAGEs (T2Ms) categories. Interestingly, several T2Ms are highly expressed in the brain and involved in the regulation of neuronal development, differentiation, and survival. Available literature suggests possible tumor suppressor functions of a few T2Ms, while information available about their expression, regulation, and clinical significance in glioma is scanty. This prompted us to perform a comprehensive analysis of T2M expression in glioma. Gene expression data from glioma datasets: Oncomine, TCGA, and REMBRANDT study, were used to assess the mRNA expression of T2M genes (MAGED1, MAGED2, MAGED3, MAGED4, MAGED4B, MAGEE1, MAGEE2, MAGEF1, MAGEH1, MAGEL2, NSMCE3, and NDN), and their association with clinical characteristics and composition of the tumor microenvironment. Further, mutation, copy number alteration, and DNA methylation data from TCGA were assessed for determining potential mechanisms of T2Ms expression in glioma. Expression analysis revealed overexpression of MAGED subfamily genes in glioma, while other genes of this family exhibited reduced expression in advanced grades of this malignancy. Further, the expression of T2Ms exhibited varying extent of positive correlations with each other. Amongst downregulated T2Ms, MAGEH1 expression exhibited negative correlations with DNA methylation. Additionally, genes associated with MAGEH1 were enriched in Myc and Hedgehog signaling. Furthermore, T2Ms downregulation was associated with immune infiltration in glioma tissues and poor overall survival of glioma patients. In multivariate Cox regression analysis, MAGEH1 emerged as an independent prognosticator in lower grade glioma. Conclusively, these results suggest that expression of T2Ms is associated with important clinical and molecular features in glioma. Mechanistic studies may further provide novel insights into their role in glioma progression.

SRRM4 Expands the Repertoire of Circular RNAs by Regulating Microexon Inclusion.

High-throughput RNA sequencing (RNA-seq) and dedicated bioinformatics pipelines have synergized to identify an expansive repertoire of unique circular RNAs (circRNAs), exceeding 100,000 variants. While the vast majority of these circRNAs comprise canonical exonic and intronic sequences, microexons (MEs)—which occur in 30% of functional mRNA transcripts—have been entirely overlooked. CircRNAs which contain these known MEs (ME-circRNAs) could be identified with commonly utilized circRNA prediction pipelines, CIRCexplorer2 and CIRI2, but were not previously recognized as ME-circRNAs. In addition, when employing a bespoke bioinformatics pipeline for identifying RNA chimeras, called Hyb, we could also identify over 2000 ME-circRNAs which contain novel MEs at their backsplice junctions, that are uncalled by either CIRCexplorer2 or CIRI2. Analysis of circRNA-seq datasets from gliomas of varying clinical grades compared with matched control tissue has shown circRNAs have potential as prognostic markers for stratifying tumor from healthy tissue. Furthermore, the abundance of microexon-containing circRNAs (ME-circRNAs) between tumor and normal tissues is correlated with the expression of a splicing associated factor, Serine/arginine repetitive matrix 4 (SRRM4). Overexpressing SRRM4, known for regulating ME inclusion in mRNAs critical for neural differentiation, in human HEK293 cells resulted in the biogenesis of over 2000 novel ME-circRNAs, including ME-circEIF4G3, and changes in the abundance of many canonical circRNAs, including circSETDB2 and circLRBA. This shows SRRM4, in which its expression is correlated with poor prognosis in gliomas, acts as a bona fide circRNA biogenesis factor. Given the known roles of MEs and circRNAs in oncogenesis, the identification of these previously unrecognized ME-circRNAs further increases the complexity and functional purview of this non-coding RNA family.

Methylation associated miR-1246 contributes to poor prognosis in gliomas treated with temozolomide

ObjectiveGlioblastoma (GBM) is the most aggressive type of glioma. In this study, we aimed to investigate the biological functions and the possible mechanisms of miR-1246 in glioma. MethodsA miRNA-seq array was conducted in both the tumor tissues and the glioma cell lines treated with 5-Aza to determine the methylation statues of miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to verify the miR-1246 expressions. We used overall survival (OS) and the progress-free survival (PFS) to investigate the clinical significance of miR-1246 in the prognosis of glioma patients. Additionally, bioinformatic analysis was used for discovering the potential targets of miR-1246. Cell viability, wound-healing assay and protein expression tests were conducted after the transfection or knockdown of miR-1246 and CCNG2, respectively. ResultsWe found the reduced expression of miR-1246 in IDH1MUT tumor tissues and the increased expression in the glioma cell lines treated with 5-Aza. Therefore, miR-1246 was selected as a candidate for further analysis. Kaplan-Meier analysis showed that the glioma patients with the high level of miR-1246 had the worst survival rate compared to the low level counterparts. Overexpression of miR-1246 promoted cell proliferation, migration and invasion in glioma cells. Moreover, the results showed that the downregulation of miR-1246 decreased chemoresistance by targeting CCNG2. In addition, Gene ontology (GO) analysis revealed that miR-1246 was associated with the regulations of transcription, cell cycle, cell proliferation, cell adhesion and apoptosis. ConclusionThese results indicated that the miR-1246/CCNG2 axis might be a potential target for improving the drug resistance in glioma.

KIF23 enhances cell proliferation in pancreatic ductal adenocarcinoma and is a potent therapeutic target.

BackgroundIn recent research, high expression of kinesin family member 23 (KIF23), one of the kinesin motor proteins involved in the regulation of cytokinesis, has been shown to be related to poor prognosis in glioma and paclitaxel-resistant gastric cancer, as a results of the enhancement of proliferation, migration, and invasion. In this study, we analyzed the role of KIF23 in the progression of pancreatic ductal adenocarcinoma.MethodsA bioinformatic method was used to analyze the KIF23 mRNA level in pancreatic tumor tissues compared with normal pancreatic tissues and to analyze the connection between high KIF23 expression and prognosis. We examined the expression of KIF23 using immunohistochemistry and analyzed the connection between the expression of KIF23 and clinicopathological features in pancreatic ductal adenocarcinoma patients. In addition, a colony formation assay, MTT assay, and western blot assay were performed in vitro, along with a mouse xenograft model in vivo, to analyze the effect of KIF23 on proliferation. Further, the correlation between KIF23 and CDCA8 was analyzed by TCGA and immunohistochemical data.ResultsBioinformatic results showed that KIF23 mRNA expression was higher in pancreatic tumor tissues than in normal pancreatic tissues and a poor prognosis has been linked to the high expression of KIF23. Immunohistochemistry revealed that KIF23 was highly expressed at the protein level and high expression of KIF23 correlated with adverse clinicopathological features. Our experimental results demonstrated that knockdown of KIF23 could inhibit the proliferation of pancreatic cells. Further, a positive correlation between KIF23 and CDCA8 expression existed, and KIF23 might promote pancreatic cancer proliferation by affecting CDCA8 expression.ConclusionsOur data showed that high expression of KIF23 is associated with a poor prognosis, and KIF23 might be a potential therapeutic target for pancreatic ductal adenocarcinoma.

Profiling pro-neural to mesenchymal transition identifies a lncRNA signature in glioma

BackgroundMolecular classification has laid the framework for exploring glioma biology and treatment strategies. Pro-neural to mesenchymal transition (PMT) of glioma is known to be associated with aggressive phenotypes, unfavorable prognosis, and treatment resistance. Recent studies have highlighted that long non-coding RNAs (lncRNAs) are key mediators in cancer mesenchymal transition. However, the relationship between lncRNAs and PMT in glioma has not been systematically investigated.MethodsGene expression profiles from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), GSE16011, and Rembrandt with available clinical and genomic information were used for analyses. Bioinformatics methods such as weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), Cox analysis, and least absolute shrinkage and selection operator (LASSO) analysis were performed.ResultsAccording to PMT scores, we confirmed that PMT status was positively associated with risky behaviors and poor prognosis in glioma. The 149 PMT-related lncRNAs were identified by WGCNA analysis, among which 10 (LINC01057, TP73-AS1, AP000695.4, LINC01503, CRNDE, OSMR-AS1, SNHG18, AC145343.2, RP11-25K21.6, RP11-38L15.2) with significant prognostic value were further screened to construct a PMT-related lncRNA risk signature, which could divide cases into two groups with distinct prognoses. Multivariate Cox regression analyses indicated that the signature was an independent prognostic factor for high-grade glioma. High-risk cases were more likely to be classified as the mesenchymal subtype, which confers enhanced immunosuppressive status by recruiting macrophages, neutrophils, and regulatory T cells. Moreover, six lncRNAs of the signature could act as competing endogenous RNAs to promote PMT in glioblastoma.ConclusionsWe profiled PMT status in glioma and established a PMT-related 10-lncRNA signature for glioma that could independently predict glioma survival and trigger PMT, which enhanced immunosuppression.

Identification of PIEZO1 as a potential prognostic marker in gliomas

In multiple solid tumours, including gliomas, the mechanical properties change as the disease progresses. If and how mechanical cues regulate tumour cell proliferation is currently not fully studied. PIEZO1 has recently been identified as a crucial mechanosensitive cation channel in multiple solid tumours. However, we didn’t find any clinical data describing the association between PIEZO1 expression and glioma. To investigate the role of PIEZO1 in gliomas, we analysed PIEZO1 gene expression at the transcriptome level, genomic profiles and the association of PIEZO1 with clinical practice. In total, 1633 glioma samples with transcriptome data, including data from the Chinese Glioma Genome Atlas RNAseq, the Cancer Genome Atlas RNAseq and GSE16011 databases, were included in this study. Clinical information and genomic profiles including somatic mutations were also obtained. We found that PIEZO1 expression was highly correlated with malignant clinical and molecular subtypes of glioma. Gene ontology analysis showed that expression of PIEZO1 was correlated with tumour microenvironment-related genes that encode proteins involved in extracellular matrix (ECM) organization, angiogenesis and cell migration. Additionally, PIEZO1 was shown to be involved in tumour progression by serving as the central checkpoint of multiple ECM remodelling-related signalling pathways to modulate tumour cell proliferation and the tumour microenvironment in turn. Finally, high PIEZO1 expression was correlated with reduced survival time and acted as a robust biomarker for poor prognosis in gliomas. Taken together, the results indicated that high PIEZO1 expression is closely associated with highly malignant gliomas. Importantly, PIEZO1 serves as a key factor involved in sensing mechanical properties in the tumour and can regulate both tumour cells and their microenvironment to promote glioma progression, and it is also a potential therapeutic target for the treatment of gliomas.

Abnormally high expression of HOXA2 as an independent factor for poor prognosis in glioma patients

ABSTRACT In recent years, studies have revealed HOXA2 as a new oncogene, but its function is unknown in gliomas. We aimed to reveal the relationship between HOXA2 and glioma based on the Chinese Glioma Genome Atlas(CGGA) and the cancer genome atlas (TCGA). HOXA2 expression data and clinically relevant information of glioma patients were obtained from the CGGA and TCGA containing 1447 glioma tissues and five non-tumor brain tissues. The Wilcox or Kruskal tests were used to detect the correlation between the HOXA2 expression level and clinical data of glioma patients. the Kaplan–Meier method were used to examine the relationship between HOXA2 and overall patient survival. Gene set enrichment analysis (GSEA) was conducted to indirectly reveal the signaling pathways involved in HOXA2, and RT-PCR was used to detect HOXA2 expression in gliomas and non-tumor brain tissues. High HOXA2 expression was found to be positively correlated with clinical grade, histological type, age, and tumor recurrence, but negatively correlated with 1p19 codeletion and isocitrate dehydrogenase mutation status.RT-PCR results showed that HOXA2 expression levels were significantly higher in tumor tissues than in non-tumor brain tissues. GSEA showed that HOXA2 promoted the activation of the activation of the JAK-STAT-signaling pathway, focal adhesion, cell-adhesion-molecules-CAMS pathway, cytosolic DNA sensing pathway, and natural killer cell-mediated cytotoxicity. This study revealed for the first time that the novel oncogene,HOXA2, leads to poor prognosis in gliomas, and can be used as a biomarker for the diagnosis and treatment of gliomas.

L1CAM High Expression Associates with Poor Prognosis in Glioma but Does Not Correlate with C11orf95-RELA Fusion.

The latest WHO guideline of CNS tumor defined a RELA fusion-positive ependymoma type with extremely poor prognosis, and the expression of L1CAM was correlated well with the presence of RELA fusion. However, the L1CAM protein expression in large sample gliomas other than ependymoma, its relationship with the RELA gene and its prognostic significance remained unknown. We examined the expression of L1CAM in 565 glioma cases (WHO grade I-IV). The L1CAM IHC-positive cases were selected to test RELA fusion with FISH break-apart probes. L1CAM was positive in 109 cases (19.29%) of all 565 glioma cases, with 18.27% in low-grade gliomas and 19.84% in high-grade gliomas, respectively. Unlike ependymoma, L1CAM protein expression was not correlated with the C11orf95-RELA fusion gene in other gliomas, but it had correction with the patient age (older than 45-year-old, p = 0.006), ATRX mutation (p = 0.003) and Ki67 (p = 0.007). High expression of L1CAM was an independent prognostic factor in our cohort. Further analysis demonstrated that L1CAM strong positive expression was significantly associated with poor prognosis in gliomas, both in our cohort (p < 0.001) and TCGA (p < 0.009) dataset. Although uncorrelated with C11orf95-RELA fusion, L1CAM was a significant poor prognostic marker in glioma patients. More aggressive treatment should be taken for these patients and L1CAM might be a promising therapeutic target in glioma.

WBSCR22 confers cell survival and predicts poor prognosis in glioma

Human WBSCR22 is involved in cancer proliferation, invasion and metastasis; however, its function in glioma remains unexplored. In our research, we aimed to investigate the role of WBSCR22 in the development of glioma and its possible molecular mechanisms. Using bioinformatic analysis of public datasets, we determined that WBSCR22 overexpression in glioma specimens was correlated with an unfavorable patient prognosis. Our results revealed that WBSCR22 was highly expressed in glioma cell lines. The loss of WBSCR22 inhibited the growth, invasion and migration of glioma cells, while WBSCR22 overexpression produced the opposite effects. Moreover, we found that WBSCR22 downregulation reduced the phosphorylation of Akt and GSK3β and decreased the levels of β-catenin and CyclinD1 in glioma cells. The opposite effects were observed when WBSCR22 was overexpressed. Additionally, we verified with a dual-luciferase reporter assay that WBSCR22 was a direct target of miR-146b-5p. Furthermore, overexpression of miR-146b-5p suppressed WBSCR22 mRNA and protein expression. Notably, the restoration of WBSCR22 expression remarkably reversed the effects of miR-146b-5p overexpression on cell survival, apoptosis and the cell cycle in glioma cells. Collectively, our findings revealed a tumor-promoting role for WBSCR22 in glioma cells, thus providing molecular evidence for WBSCR22 as a novel therapeutic target in glioma.