Brain Lower Grade Glioma Research Articles

Comprehensive Pan-cancer analysis of CD73: explore its association with prognosis and tumor immune microenvironment

BackgroundCD73 is adenosine generation molecule, which is involved in the immune regulation. However, the roles of CD73 in the tumor microenvironment remain unknown. MethodsCD73 expression levels in pan-cancers were analyzed, based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Human Protein ALTAS (HPA) databases. Kaplan-Meier (KM) plotter was used to analyze the prognostic values of CD73. Immune scores in pan-cancers was evaluated by ESTIMATE. TIMER2.0 and UCSCXena were used to explore the correlation between CD73 and immune infiltration/immune checkpoints/tumor mutation burden (TMB)/microsatellite instability (MSI). CD73 expression correlated genes in tumor tissues were screened by using LinkedOmics tool. ResultsFirstly, CD73 was significant increased in following cancer types: esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), brain lower grade glioma (LGG), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD) and stomach adenocarcinoma (STAD). Secondly, high CD73 expression was associated with poor overall survival in patients with breast invasive carcinoma (BRCA), CESC, HNSC, liver hepatocellular carcinoma (LIHC), LUAD, lung squamous cell carcinoma (LUSC), PAAD and STAD. However, in KIRC and UCEC, patients high CD73 expression showed a favorable prognosis. Thirdly, the immune scores of the high CD73 expression in bladder urothelial carcinoma (BLCA), BRCA, kidney chromophobe (KICH), LUAD, LUSC, ovarian serous cystadenocarcinoma (OV), pheochromocytoma and paraganglioma (PCPG), prostate adenocarcinoma (PRAD), and skin cutaneous melanoma (SKCM) were significant higher than that of patients with low CD73 expression. Furthermore, we observed a positive correlation between CD73 and the multiple immune cells infiltration, including CD4+ memory T cells, CD8+ T cells, Treg cells, myeloid DC and macrophage, particularly in BRCA and LUAD. There was no strong correlation between CD73 and TMB/MSI. In LUAD, CD73 expression correlated genes were mainly enrichment in positive regulation of cell proliferation, cell adhesion, positive regulation of kinase activity, cellular response to LPS. However, in UCEC, CD73 correlated genes were mainly associated with fatty acid omega-oxidation, protein localization to endoplasmic reticulum exit site, endoplasmic reticulum to Golgi vesicle-mediated transport. ConclusionCD73 could be used to predict the prognosis of patients with several cancers. The potential functional mechanism of CD73 involved in cancer progress may not only dependent on its immunomodulatory effects.

EBNA1BP2 identified as potential prognostic biomarker for multiple tumor types in pan-cancer analysis

BackgroundEpstein-Barr virus (EBV) infection has been closely linked to the development of various types of cancer. EB nuclear antigen 1 binding protein 2 (EBNA1BP2) is a crucial molecule for stable isolation of EBV in latent infection. However, the role of EBNA1BP2 in multiple tumor types is remains unclear. In this study, we comprehensively analyzed the functional characteristics of EBNA1BP2 and investigate its potential as a prognostic biomarker in pan-cancer.MethodsWe utilized data from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) databases and employed various bioinformatics analysis tools, including TIMER2.0, HPA, GEPIA2.0, PrognoScan, cBioPortal, CancerSEA, and BioGRID to explore the expression pattern, prognostic value, immune infiltration, and methylation level of EBNA1BP2 in pan-cancer. Additionally, we conducted enrichment analysis of genes associated with EBNA1BP2 to identify potential biological functions and pathways.ResultsOur analysis revealed that EBNA1BP2 expression was significantly higher in tumor tissues compared to tumor-adjacent tissues. We observed that lower expression of EBNA1BP2 in adrenocortical carcinoma (ACC), brain lower grade glioma (LGG), sarcoma (SARC), and uterine carcinosarcoma (UCS) was significantly associated with improved overall survival (OS) and disease-free survival (DFS). Furthermore, the promoter methylation level of EBNA1BP2 was downregulated in the majority of cancer types. At the single-cell level, EBNA1BP2 was found to be positively correlated with cell cycle and DNA repair processes, while negatively correlated with hypoxia. Additionally, EBNA1BP2 was associated with the infiltration of immune cells such as B cells, cancer-associated fibroblast cells, and CD8+ T cells. Gene enrichment analysis indicated that EBNA1BP2 was mainly involved in nucleoplasm and RNA binding pathways.ConclusionOur findings suggest that EBNA1BP2 may serve as a potential prognostic biomarker for survival in pan-cancer. Further experimental studies are needed to validate these findings and explore the underlying mechanisms by which EBNA1BP2 contributes to tumorigenesis.

Selenoprotein S (SELENOS) is a potential prognostic biomarker for brain lower grade glioma

BackgroundSelenium, an essential micronutrient, primarily exists as selenocysteine in various selenoproteins. Selenoprotein S (SELENOS) is crucial in the development of human cancer. This study aimed to explore the correlation between SELENOS gene expression and the prognosis of brain lower-grade glioma (LGG). MethodsSELENOS protein and mRNA expression in human normal and tumor tissues were explored through the HPA database. SELENOS expression differences between normal and tumor tissues, along with its prognostic significance in gliomas, were analyzed using the TCGA, GTEx datasets, while the CGGA dataset was used to further assess its prognostic potential in a Chinese cohort. The association between SELENOS expression and tumor immune infiltration was also assessed. Multivariate and univariate Cox models were used to screen for clinicopathological parameters associated with SELENOS expression. The GDSC datasets was utilized to explore the connection between SELENOS and chemotherapeutic responses in LGG. A protein-protein interaction network for SELENOS was created. SELENOS expression in LGG cell lines were determined by Western blotting and qRT-PCR, and its functions were ascertained by routine in vitro experiments. ResultsSELENOS was upregulated in 11 cancers and downregulated in 10 cancers relative to the corresponding normal tissues, and correlated significantly with the prognosis, especially for GBM, LGG and GBMLGG. Furthermore, It displayed a positive correlation with immune cell infiltration levels in LGG. Multivariate and Univariate Cox analyses confirmed that the impact of SELENOS on the prognosis of LGG is the combined result of factors such as age and tumor grade. The expression of SELENOS was significantly negatively correlated with temozolomide IC50 in LGG. We found that SELENOS interacts with 10 proteins, which are upregulated in LGG compared to human normal tissues. The expression of these interactors is positively correlated with SELENOS expression and LGG survival/prognosis. In vitro experiments confirmed the aberrant expression of SELENOS in LGG cell lines, and siRNA-mediated knockdown of SELENOS reduced the proliferation, viability, invasion and migration of LGG cells, and induced apoptosis. ConclusionsSELENOS is a potential prognostic marker and therapeutic target for LGG, and its low expression is associated with favorable prognosis in LGG.

A novel approach to the analysis of Overall Survival (OS) as response with Progression-Free Interval (PFI) as condition based on the RNA-seq expression data in The Cancer Genome Atlas (TCGA)

BackgroundOverall Survival (OS) and Progression-Free Interval (PFI) as survival times have been collected in The Cancer Genome Atlas (TCGA). It is of biomedical interest to consider their dependence in pathway detection and survival prediction. We intend to develop novel methods for integrating PFI as condition based on parametric survival models for identifying pathways associated with OS and predicting OS.ResultsBased on the framework of conditional probability, we developed a family of frailty-based parametric-models for this purpose, with exponential or Weibull distribution as baseline. We also considered two classes of existing methods with PFI as a covariate. We evaluated the performance of three approaches by analyzing RNA-seq expression data from TCGA for lung squamous cell carcinoma and lung adenocarcinoma (LUNG), brain lower grade glioma and glioblastoma multiforme (GBMLGG), as well as skin cutaneous melanoma (SKCM). Our focus was on fourteen general cancer-related pathways. The 10-fold cross-validation was employed for the evaluation of predictive accuracy. For LUNG, p53 signaling and cell cycle pathways were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI. For GBMLGG, ten pathways (e.g., Wnt signaling, JAK-STAT signaling, ECM-receptor interaction, etc.) were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated better predictive performance compared to the approaches without the consideration of PFI. For SKCM, p53 signaling pathway was detected only by our Weibull-baseline-based model. And three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI.ConclusionsBased on our study, it is necessary to incorporate PFI into the survival analysis of OS. Furthermore, PFI is a survival-type time, and improved results can be achieved by our conditional-probability-based approach.

Direct DNA binding by BRCA1 on β-hCG promoter and its clinical implications

ObjectiveThe role of β-hCG in breast cancer is largely unknown, this study aims to analyse the gene expression and clinical implications of β-hCG and its isoforms in various cancers focussing particularly in Breast Invasive Carcinoma (BRCA). A mechanistic approach deciphering the transcriptional regulation of β-hCG by BRCA1 was also explored. MethodsData from various comprehensive gene expression platforms like UALCAN, GEPIA2, GENT2, TIMER2, LinkedOmics, and STRING were used to analyse the expression of β-hCG and its clinical implications; Immunohistochemistry and ELISA for β-hCG expression analysis from human breast cancer patients; Electrophoretic mobility shift assay (EMSA) to analyse the direct binding of BRCA1 on β-hCG; Immunoblotting and Luciferase assay to understand the regulation of β-hCG by p53 were performed. ResultsResults from UALCAN and GENT2 gene expression cancer database revealed that TNBC subtypes and high-grade metaplastic carcinoma shows elevated expression of β-hCG and infiltration of various immune cells were also identified in BRCA by TIMER2. It was observed that most of the isoforms of β-hCG (CGB) are upregulated in breast cancers irrespective of hormonal status when BRCA1 gene is mutated according to TIMER2. Similar results were observed with Lymphoid neoplasm diffuse large B-cell lymphoma (LGG) and DLBC (Brain lower grade glioma) when BRCA1 is mutated. These results correlate with our earlier reports indicating expression of β-hCG in BRCA1 defective condition. We have also identified direct binding of BRCA1 on β-hCG promoter. ConclusionAll these findings demonstrate the importance of β-hCG as a potential target in BRCA1-deficient carcinomas.

Pan-Cancer Analysis Reveals Long Non-coding RNA (lncRNA) Embryonic Stem Cell-Related Gene (ESRG) as a Promising Diagnostic and Prognostic Biomarker.

Embryonic stem cell-related gene (ESRG; also known as HESRG) is a long non-coding RNA (lncRNA). It is involved in the regulation of human pluripotent stem cells (hPSCs) self-renewal. ESRG gene has the ability to interact with chromatins, different RNA types, and RNA binding proteins (RBP); thus making ESRG be considered an oncogenic lncRNA, where its expression is detected in various tumor tissues. This study aimed to evaluate the prospective diagnostic and prognostic values of ESRG in various human cancers. The expression of ESRG in various cancers was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) databases. Moreover, the correlation between the expression of ESRG and clinical pathological parameters was analyzed using UALCAN. The effect of ESRG expression on the survival outcome was evaluated using Kaplan-Meier plotter, UALCAN, GEPIA, and TIMER. The correlation between ESRG expression and immune cell infiltration was studied by TIMER. Additionally, the genetic alterations were investigated cBioportal. Our findings were validated using the GEO2R database. Our results showed ESRG to be significantly up-regulated incolon adenocarcinoma (COAD) and lung squamous cell carcinoma (LUSC) with p<0.001, in addition to rectum adenocarcinoma (READ), and uterine carcinosarcoma (UCEC) withp<0.01. Regarding pathogenic stages, there was a significant upregulation in stages 2, 3, and 4 compared to normal in COAD and stages 1, 2, and 3 for LUSC patients. The combined prognostic analysis showed that the up-regulated expression of ESRG was associated with better survival outcomes in patients with brain lower-grade glioma (LGG). Our results demonstrate a significant negative correlation between ESRG expression and the abundance of CD8+T cells in COAD, READ, LUSC, and UCEC. Additionally, ESRG was mutated in 0.77 (<1%) of the queried samples, and the most prevalent ESRG mutations are deep deletion mutations, followed by amplification. Analysis of ESRG across various cancer types elucidated its potential to be used as a diagnostic biomarker in COAD, LUSC, READ, and UCEC and a promising prognostic biomarker in LGG. Our findings provide useful insights for future research.

Pan-cancer analysis and single-cell analysis reveals FAM110B as a potential target for survival and immunotherapy.

Background: FAM110B belongs to the family that has a 110 sequence similarity (FAM110) and is located in the centrosome and mitotic spindle. FAM110B has been linked to tumor cell growth in earlier research. Uncertainty exists regarding FAM110B's function within the tumor microenvironment is unclear as well as pan-cancer. Methods: In order to assess the variation in FAM110B expression within normal and pan-cancer tissues, we combined the TCGA and GTEx databases. The cBioPortal database and the GSCALite platform were used to examine the variation in genome and methylation alteration of FAM110B. Cox regression, Kaplan-Meier, and SangerBox were employed to examine the clinical features and prognosis of FAM110B and pan-cancer. The purpose of the correlational research was to investigate the associations within immunerelated genes, tumor mutation burden, microsatellite instability, immune-related genes, and immunological checkpoints and FAM110B expression. ESTIMATE, EPIC, QUANTISEQ, and MCPCOUNTER methods were used to calculate the interaction among FAM110B expression as well as the tumor immune microenvironment. The immunoinfiltration and function of FAM110B were analyzed by single-cell databases (TISCH and CancerSEA). Finally, we evaluated the sensitivity of FAM110B to small-molecule medications through GDSC and CTRP databases. Results: The transcription and protein expression of FAM110B varies significantly throughout cancer types, and this has predictive value for the prognosis of some tumors; including brain lower grade glioma (LGG), stomach adenocarcinoma (STAD), pancreatic adenocarcinoma (PAAD), etc. In the tumor microenvironment, the expression level of FAM110B was associated with immune cell infiltration, immune checkpoint immune regulatory genes, tumor mutational burden, and microsatellite fragility to a certain extent. Conclusion: This work investigates the possibility of utility of FAM110B as a marker to forecast pan-cancer immunotherapy response, providing a theoretical basis for cancer therapy.

Higher YAP1 Levels Are Associated With Shorter Survival of Patients With Low Grade Astrocytoma.

Glioblastoma multiforme (GBM) is one of the most lethal types of brain cancer with a median survival of only 12 months due to its aggressiveness and lack of effective treatment options. Astrocytomas and oligodendrogliomas are classified as low-grade gliomas (LGG) and have the potential to progress into secondary GBM. YAP1 and TAZ are transcriptional co-activators of the hippo pathway and play an important role in tumorigenesis by controlling cell proliferation and differentiation. The aim of this study was to analyze whether YAP1 and TAZ influence the survival in patients with astrocytoma and oligodendroglioma. A total of 22 patient samples of astrocytoma and 11 samples of oligodendroglioma were analyzed using real-time PCR. We utilized open-access data from The Cancer Genome Atlas (TCGA) focusing on "brain lower grade glioma". mRNA expression rates were used to validate our findings on survival analysis. Expression of YAP1 was twice as high in astrocytoma than in oligodendroglioma, whereas there was no difference in TAZ. In oligodendrogliomas, the expression of TAZ was higher in relapsed than in primary tumors. Patients with astrocytoma having a high YAP1 expression had a significantly shorter overall survival than patients with lower expression (median survival 161 vs. 86 months, p=0.0248). These findings were validated with survival analysis of TCGA data. High YAP1 expression shows a high correlation with poorer overall survival in LGG. YAP1 has higher levels of expression in astrocytomas than in oligodendrogliomas.

A comprehensive prognostic and immune analysis of FDX1 in brain lower grade glioma

A comprehensive prognostic and immune analysis of FDX1 in brain lower grade glioma

Selenoprotein GPX3 is a novel prognostic indicator for stomach adenocarcinoma and brain low-grade gliomas: Evidence from an integrative pan-cancer analysis

BackgroundThe antioxidant enzyme GPX3 is a selenoprotein that transports selenium in blood and maintains its levels in peripheral tissues. Aberrant GPX3 expression is strongly linked to the development of some tumors. However, there is a scarcity of studies examining the pan-cancer expression patterns and prognostic relevance of GPX3. MethodsGPX3 expression levels in normal tissues and multiple tumors were analyzed using TCGA, CCLE, GTEx, UALCAN and HPA databases. Forest plots and KM survival curves were utilized to evaluate the correlation between GPX3 expression and the outcome of tumor patients. The prognostic value of GPX3 in LGG was assessed utilizing the CGGA datasets, and that in STAD was tested by TCGA and GEO databases. A nomogram was then constructed to predict OS in STAD using R software. Additionally, the impact of GPX3 on post-chemoradiotherapy OS in patients with LGG and STAD was evaluated using the KM method. The multiplicative interaction of GPX3 expression, chemotherapy and radiotherapy on STAD and LGG was analyzed using logistic regression models. The correlation of GPX3 with the immune infiltration, immune neoantigens and MMR genes were investigated in TCGA cohort. ResultsGPX3 exhibited downregulation across 21 tumor types, including STAD, with its decreased expression significantly associated with improved OS, DFS, PFS and DSS. Conversely, in LGG, low levels of GPX3 expression were indicative of a poorer prognosis. Univariate and multivariate Cox models further identified GPX3 as an independent predictor of STAD, and a nomogram based on GPX3 expression and other independent factors showed high level of predictive accuracy. Moreover, low GPX3 expression and chemotherapy prolonged the survival of STAD. In LGG patients, chemoradiotherapy, GPX3 and chemotherapy, and GPX3 and chemoradiotherapy may improve prognosis. Our observations reveal a notable connection between GPX3 and immune infiltration, immune neoantigens, and MMR genes. ConclusionsThe variations in GPX3 expression are linked to the controlling tumor development and could act as a promising biomarker that impacts the prognosis of specific cancers like STAD and LGG.

RPN1: a pan-cancer biomarker and disulfidptosis regulator.

Elevated expression of SLC7A11, in conjunction with glucose deprivation, has revealed disulfidptosis as an emerging cell death modality. However, the prevalence of disulfidptosis across tumor cell lines, irrespective of SLC7A11 levels, remains uncertain. Additionally, deletion of the ribophorin I (RPN1) gene imparts resistance to disulfidptosis, yet the precise mechanism linking RPN1 to disulfidptosis remains elusive. The aim of this study is to determine the mechanism of RPN1-induced disulfidptosis and to determine the possibility of RPN1 as a pan-cancer marker. We hypothesized the widespread occurrence of disulfidptosis in various tumor cells, and proposed that RPN1-mediated disulfidptosis may be executed through cell skeleton breakdown. Experimental validation was conducted via flow cytometry, immunofluorescence, and western blot techniques. Furthermore, given RPN1's status as an emerging cell death marker, we utilized bioinformatics to analyze its expression in tumor tissues, clinical relevance, mechanisms within the tumor microenvironment, and potential for immunotherapy. Conducting experiments on breast cancer (MDA-MB-231) and lung cancer (A549) cell lines under glucose-starved conditions, we found that RPN1 primarily induces cell skeleton breakdown to facilitate disulfidptosis. RPN1 demonstrated robust messenger RNA (mRNA) expression across 16 solid tumors, validated by data from 12 tumor types in the Gene Expression Omnibus (GEO). Across 12 cancer types, RPN1 exhibited significant diagnostic potential, particularly excelling in accuracy for glioblastoma (GBM). Elevated RPN1 expression in tumor tissues was found to correlate with improved overall survival (OS) in certain cancers [diffuse large B-cell lymphoma (DLBC) and thymoma (THYM)] but poorer prognosis in others [adrenocortical carcinoma (ACC), kidney chromophobe (KICH), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD)]. RPN1 is enriched in immune-related pathways and correlates with immune scores in tumor tissues. In urothelial carcinoma (UCC), RPN1 demonstrates potential in predicting the efficacy of anti-programmed cell death ligand 1 (PD-L1) immune therapy. This study underscores RPN1's role in facilitating disulfidptosis, its broad relevance as a pan-cancer biomarker, and its association with the efficacy of anti-PD-L1 immune therapy.

Multi-Omics Pan-Cancer Analysis of Procollagen N-Propeptidase Gene Family of ADAMTS as Novel Biomarkers to Associate with Prognosis, Tumor Immune Microenvironment, Signaling Pathways, and Drug Sensitivities.

The extracellular matrix (ECM) modeling induced by the metalloproteinases is a vital characteristic for tumor progression. Previous studies mainly focus on the functions of two subgroups of metalloproteinases: matrix metalloproteinases (MMPs) and a disintegrin and metalloproteases (ADAMs) in tumors. The roles of another important group: the ADAMs with thrombospondin motifs (ADAMTS) remain unclear. This study aimed to perform a pan-cancer analysis of procollagen N-propeptidase subgroup of ADAMTS (PNPSA). We systematically analyzed expression landscape, genomic variations, prognostic value, and cell expression clusters of PNPSA in pan-cancer based on the multiple integrated open databases. Besides, we also analyzed the impacts of expressions and genomic variations of PNPSA members on tumor immune microenvironment (TIME) and immune-related molecules in pan-cancer based on the immune-related open databases. The Gene Set Variation Analysis (GSVA) was performed to evaluate the associations of the whole PNPSA with prognosis, tumor indicators, TIME, and drug sensitivities. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to reveal related signaling pathways. Finally, immunohistochemical staining was used to validate the differential analysis results. We found a dual prognostic role of PNPSA members in pan-cancer and they were significantly correlated with TIME and immune-related molecules. Interestingly, the copy number variations (CNVs) of all PNPSA members were revealed to be negatively correlated with NK cell infiltration in most cancers. Single-cell sequencing analysis reveals expressions of PNPSA gene family members on some specific tumor and immune cells in addition to the fibroblasts. The GSVA score was found to have some predictive value for survival status in Brain Lower Grade Glioma (LGG), Mesothelioma (MESO), and Uveal Melanoma (UVM) and to be significantly correlated with tumorigenesis-related pathways such as PI3K-Akt, AGE-RAGE, etc. The GSVA score also shows some predictive value for chemotherapy and immunotherapy efficacy in some tumors. PNPSA was correlated with tumor development and might be potential tumor biomarker and therapeutic target.

ESCO2’s oncogenic role in human tumors: a pan-cancer analysis and experimental validation

PurposeEstablishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function.MethodsWe thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2’s impacts on clear cell renal cell carcinoma (ccRCC) cells’ proliferative and invasive capacities in vitro.ResultsIn our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2’S knockdown significantly inhibited the A498 and T24 cells’ proliferation, invasion, and migration.ConclusionsIn conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.

Gene Expression of GABAA Receptor Subunits and Association with Patient Survival in Glioma.

Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABAA receptors. The GABRA5 gene, which encodes the α5 subunit of the GABAA receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABAA receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABAA receptor subunits in different types of glioma, and its possible association with patient prognosis assessed by overall survival (OS). Data were obtained from the French and The Cancer Genome Atlas Brain Lower Grade Glioma (TCGA-LGG) datasets and analyzed for expression of GABAA receptor subunit genes. OS was calculated using the Kaplan-Meier estimate. We found that genes GABRA2, GABRA3, GABRB3, GABRG1, and GABRG2 showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of GABRA2 was associated with shorter OS, whereas, in contrast, higher levels of GABRB3 were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, GABRA3, GABRB3, GABRG1, and GABRG2, were associated with longer OS. High GABRB3 expression was related to longer survival when low grade glioma types were analyzed separately. Our results suggest an overall association between higher expression of most genes encoding GABAA receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABAA receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABAA receptors as a therapeutic target in glioma.

Pan-cancer analysis predicts CANT1 as a potential prognostic, immunologic biomarker

BackgroundCANT1, calcium-activated nucleotidase 1, was reported to be upregulated in certain tumors. However, the function mechanism of CANT1 in pan-cancer is still unclear. MethodsWe utilized the Cancer Genome Atlas Program (TCGA) and UALCAN databases to analyze CANT1 expression at the level of mRNA, protein, and promoter methylation in pan-cancer, and the cBioportal database to study the frequency of gene changes for CANT1. Wilcoxon test was applied to discuss the correlation between CANT1 and clinicopathological features in different tumor types. The prognosis of CANT1 in pan-cancer was discussed by Cox regression. Spearman analysis was applied to discuss the relationship of CANT1 with tumor mutation burden(TMB), microsatellite instability(MSI), immune cell infiltration, and immune checkpoints. The association between CANT1 expression and drug sensitivity for pan-cancer was investigated by the GSCALite database. In addition, we collected 40 cases of lung adenocarcinoma (LUAD) and adjacent normal tissues for immunohistochemical staining and investigated the relationship between CANT1 and clinicopathology and prognosis in LUAD. Finally, the molecular pathways involved in CANT1-related genes in LUAD were analyzed by gene set enrichment analysis(GSEA). ResultsThe CANT1 mRNA level was significant higher in 14 tumors, and CANT1 protein level was significant higher in 7 tumors compared with normal tissues. CANT1 expression was linked with the T stage, N stage, and pathological stage in some tumors, and overexpression CANT1 was associated with adverse overall survival(OS) and disease-specific survival(DSS) in kidney renal papillary cell carcinoma(KIRP), brain lower grade glioma(LGG), and LUAD. By Spearman correlation analysis, the results showed that CANT1 had a positive correlation with TMB and MSI in bladder urothelial carcinoma(BLCA), breast invasive carcinoma(BRCA), esophageal carcinoma(ESCA), LGG, and sarcoma(SARC). Furthermore, CANT1 was related to immune cell infiltration and immune checkpoints in several cancers. Drug sensitivity analysis suggested that CANT1 was inversely linked with three drugs. Immunohistochemical staining analysis showed that CANT1 expression was higher in LUAD than in normal tissues, and was related to N stage and pathological stage. Survival curves showed that CANT1 overexpression had poor OS and DSS. Time-dependent ROC curves revealed that the 1-year, 5-year, and 10-year OS and DSS in LUAD were above 0.5. CANT1-related genes in LUAD mainly participated in the pathway of dorso ventral axis formation, small cell lung cancer, DNA replication, O-glycan biosynthesis, and cell cycle. ConclusionCANT1 is considered a potential marker for prognosis in several tumors, and a promising target for tumor immunological treatment.

Delving into the Role of Receptor-like Tyrosine Kinase (RYK) in Cancer: In Silico Insights into Its Diagnostic and Prognostic Utility

The RYK gene encodes a receptor-like tyrosine kinase crucial for several biological processes, including development, tissue homeostasis, and cancer. This study utilized data from the Cancer Genome Atlas Project (TCGA) to evaluate RYK expression at both mRNA and protein levels in various cancers, determine its prognostic significance, and explore its involvement in cancer-related signaling pathways. Elevated levels of RYK mRNA were identified in cholangiocarcinoma (CHOL), pancreatic adenocarcinoma (PAAD), glioblastoma multiforme (GBM), lung squamous cell carcinoma (LUSC), brain lower grade glioma (LGG), head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LICH), esophageal carcinoma (ESCA), and colon adenocarcinoma (COAD), while RYK protein levels were observed to be increased in colon adenocarcinoma (COAD), GBM, LICH, cervical and endocervical adenocarcinoma (CESC), and breast invasive carcinoma (BRCA). Additionally, RYK overexpression correlated with poorer prognosis in several cancers, including PAAD, LICH, BRCA, ESCA, COAD, and CESC. Furthermore, RYK showed a positive correlation with the upregulation of multiple receptors and coreceptors in the WNT signaling pathway in various types of cancer. In terms of cancer-related signaling pathways, RYK was found to potentially interact with DNA damage, TSC/mTOR, PI3K/AKT, EMT, RTK, RAS/MAPK, ER hormone, AR hormone, and the cell cycle. This study provides new and previously unreported insights into the role of RYK in cancer biology.

Systematic pan-cancer analyses of the potential function of the Golgi scaffold protein PAQR3

Progesterone and AdipoQ Receptor 3 (PAQR3) is a member of the AdipoQ receptor. Our previous studies have found that PAQR3 plays a role as a candidate inhibitor in cardiac adenocarcinoma, breast cancer, gastric cancer and colorectal cancer, but the systematic analysis of PAQR3 in tumors is currently lacking. The objective of this study was to investigate the prognostic and therapeutic value of PAQR3 in 31 tumors. Through the analysis of TCGA, UALCAN, GEO, GEPIA2, TIMER, Kaplan–Meier plotter, TISIDB and other databases, it was found that the expression level of PAQR3 changed significantly in different tumor types, and the expression level of Neuroblastoma was very high. And the level of Prostate adenocarcinoma is low. In addition, the expression level of PAQR3 in Cholangiocarcinoma, Esophageal carcinoma, Head and neck squamous carcinoma, Liver Hepatocellular Carcinoma, Lung Adenocarcinoma and Lung squamous cell carcinoma was significantly higher than that in normal tissues. However, the expression level of PAQR3 in Breast Cancer, Kidney Renal Clear Cell Carcinoma, Kidney renal papillary cell carcinoma, Prostate Adenocarcinoma, Rectum Adenocarcinoma, Thyroid Cancer and Uterine Corpus Endometrial Carcinoma was lower than that in normal tissues. Subsequently, we explored the value of PAQR3 as a prognostic indicator of cancer. In Acute Myeloid Leukemia, Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Kidney Chromophobe, and Thyroid Cancer, PAQR3 expression was positively correlated with OS and DSS, while in Rectum Adenocarcinoma, PAQR3 expression was negatively correlated with OS. PAQR3 high expression group Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Uveal Melanoma, Kidney Chromophobe and DFI were positively correlated. PAQR3 can be used as a risk factor for the prognosis of multiple tumors. Then, we discussed the correlation between PAQR3 and immunology, and found that PAQR3 has a wide range of mutations in various tumor types, the most common mutation type is missense mutation, and common mutation types also include amplification, depth deletion, splicing, truncation and structural variation. Among the tumor samples with PAQR3 alterations, mutation occurred in all tumor samples except prostate adenocarcinoma and adrenal cortical carcinoma, head and neck squamous cell carcinoma, brain low-grade glioma, and kidney clear cell carcinoma, while esophageal adenocarcinoma had the highest total alteration frequency. PAQR3 was strongly associated with CNV in 18 tumors, particularly in Ovarian cancer, Lung squamous cell carcinoma, and Adenoid cystic carcinoma. On the other hand, PAQR3 has a higher SNV frequency in Uterine Corpus Endometrial Carcinoma, Skin Cutaneous Melanoma and Lung Adenocarcinoma, among which Uterine Corpus Endometrial Carcinoma has the highest SNV frequency. These results showed that PAQR3 expression levels were significantly correlated with tumor mutation load, microsatellite instability, neoantigens, and purity. In summary, PAQR3 can affect the tumor microenvironment and has potential for chemotherapy. Finally, we investigated the role of PAQR3 in tumor resistance and found that the expression of PAQR3 affects the efficacy of multiple chemotherapy drugs. Based on these studies, we found that PAQR3 plays an important role in cancer and has potential in tumor diagnosis and prognosis.

Comprehensive Analysis of the Role of Forkhead Box J3 (FOXJ3) in Human Cancers

Forkhead box J3 (FOXJ3) is a member of the forkhead box (Fox) family. Recently, increasing evidence has revealed the relationship between Fox family members and cancer. FOXJ3 is involved in various types of cancer, including lung cancer, tongue squamous carcinoma, and prostate cancer; however, a comprehensive pan-cancer analysis of FOXJ3 remains lacking. Here, we explored the function of FOXJ3 across cancers using online websites and databases including TIMER2.0, SangerBox, UALCAN, GEPIA2.0, cBioPortal, CancerSEA,STRING, BioGRID and Metascape to analyze the role of FOXJ3 in cancers. Abnormal expression of FOXJ3 was found in various tumors. The genetic alteration percentage in tumors was determined, and elevated FOXJ3 expression was found to be associated with worse overall survival in brain lower grade glioma(LGG), liver hepatocellular carcinoma (LIHC), sarcoma (SARC) and thyroid carcinoma. Elevated FOXJ3 expression was related to worse prognosis with disease-free survival in adrenocortical carcinoma, LGG and LIHC. FOXJ3 expression was related to immune infiltration in several cancers. Enrichment analysis showed that histone modification, the TGF-β signaling pathway, and chromatin organization were the top three enriched ontology clusters of the top 100 similar genes of FOXJ3. Our pan-cancer analysis provides comprehensive insights into FOXJ3 from the perspective of bioinformatics in different cancers, where it serves as a potential biomarker for prognosis, especially in LGG and LIHC. FOXJ3 is also correlated with immune infiltrates in certain human tumors.

Pan-cancer and single-cell analysis reveal THRAP3 as a prognostic and immunological biomarker for multiple cancer types

Background: Thyroid hormone receptor-associated protein 3 (THRAP3) is of great significance in DNA damage response, pre-mRNA processing, and nuclear export. However, the biological activities of THRAP3 in pan-cancer remain unexplored. We aimed to conduct a comprehensive analysis of THRAP3 and validate its expression levels in lung cancer.Methods: A pan-cancer analysis was conducted to study the correlation of THRAP3 expression with clinical outcome and the tumor microenvironment based on the available bioinformatics databases. The protein levels of THRAP3 were explored in lung cancer by immunohistochemistry (IHC) analysis. Single-cell sequencing (ScRNA-seq) analysis was employed to investigate the proportions of each cell type in lung adenocarcinoma (LUAD) and adjacent normal tissues, along with the expression levels of THRAP3 within each cell type.Results: THRAP3 is upregulated in multiple cancer types but exhibits low expression in lung squamous cell carcinoma (LUSC). immunohistochemistry results showed that THRAP3 is a lowly expression in LUAD and LUSC. THRAP3 elevation had a poor prognosis in kidney renal clear cell carcinoma and a prolonged survival time in kidney chromophobe, brain lower-grade glioma and skin cutaneous melanoma, as indicated by the KM curve. Single-cell analysis confirmed that the proportions of T/B cells, macrophages, and fibroblasts were significantly elevated in LUAD tissues, and THRAP3 is specifically overexpressed in mast cells.Conclusion: Our findings uncover that THRAP3 is a promising prognostic biomarker and immunotherapeutic target in multiple cancers, but in LUAD and LUSC, it may be a protective gene.

Pan-Cancer Analysis of P3H1 and Experimental Validation in Renal Clear Cell Carcinoma.

Prolyl 3-hydroxylase 1 (P3H1) has been implicated in cancer development, but no pan-cancer analysis has been conducted on P3H1. In this study, for the first time, aspects associated with P3H1, such as the mRNA expression, any mutation, promoter methylation, and prognostic significance, the relationship between P3H1 and clinicopathological parameters, drug sensitivity, and immune cell infiltration were investigated by searching several databases including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), cBioPortal, and The Tumor Immune Evaluation Resource (TIMER2.0) using bioinformatics tools. The findings indicate significant differential expression of P3H1 in most tumors when compared to normal tissues, with a strong association with clinical prognosis. A pan-cancer Cox regression analysis revealed that high P3H1 expression is significantly associated with low overall survival in patients with brain lower grade glioma, kidney clear cell carcinoma, adrenocortical cancer, liver hepatocellular carcinoma, mesothelioma, sarcoma, uveal melanoma, bladder urothelial carcinoma, kidney papillary cell carcinoma, kidney chromophobe, thymoma, and thyroid carcinoma. A negative correlation was observed between P3H1 DNA methylation and its expression. P3H1 is significantly associated with infiltrating cells, immune-related genes, tumor mutation burden, microsatellite instability, and mismatch repair. Finally, A significant correlation was found between P3H1 expression and sensitivity to nine drugs. Thus, enhanced P3H1 expression is associated with poor prognosis in a variety of tumors, which may be due to its role in tumor immune regulation and tumor microenvironment. This pan-cancer analysis provides insight into the function of P3H1 in tumorigenesis of different cancers and provides a theoretical basis for further in-depth studies to follow.