MAPK Activated Protein Kinase 3 Is a Prognostic-Related Biomarker and Associated With Immune Infiltrates in Glioma.
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ABSTRACT:
SUBMITTER: Ren J
PROVIDER: S-EPMC8685266 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundGlioma is the most frequent type of malignancy that may damage the brain with high morbidity and mortality rates and patients' prognoses are still dismal. Ferroptosis, a newly uncovered mode of programmed cell death, may be triggered to destroy glioma cells. Nevertheless, the significance of ferroptosis-related genes (FRGs) in predicting prognosis in glioma individuals is still a mystery.MethodsThe CGGA (The Chinese Glioma Atlas), GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas) databases were all searched to obtain the glioma expression dataset. First, TCGA was searched to identify differentially expressed genes (DEGs). This was followed by a machine learning algorithm-based screening of the glioma's most relevant genes. Additionally, these genes were subjected to Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional enrichment analyses. The chosen biological markers were then submitted to single-cell, immune function, and gene set enrichment analysis (GSEA). In addition, we performed functional enrichment and Mfuzz expression profile clustering on the most promising biological markers to delve deeper into their regulatory mechanisms and assess their clinical diagnostic capacities.ResultsWe identified 4444 DEGs via differential analysis and 564 FRGs from the FerrDb database. The two were subjected to intersection analysis, which led to the discovery of 143 overlapping genes. After that, glioma biological markers were identified in fourteen genes by the use of machine learning methods. In terms of its use for clinical diagnosis, SMG9 stands out as the most significant among these biomarkers.ConclusionIn light of these findings, the identification of SMG9 as a new biological marker has the potential to provide information on the mechanism of action and the effect of the immune milieu in glioma. The promise of SMG9 in glioma prognosis prediction warrants more study.
| S-EPMC10878878 | biostudies-literature
Project description:BackgroundCell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it's role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear.MethodsIn this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells.ResultsAs a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05).ConclusionIn conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.
| S-EPMC9316328 | biostudies-literature
Project description:ObjectiveGliomas are the most common and life-threatening intracranial tumors. Immune infiltration of the tumor microenvironment significantly affects tumor prognosis in glioma. Recently, PLEKHA4 was reported to be upregulated in melanoma and closely associated with tumor genesis and development, but its role in glioma is poorly understood. Our aim was to investigate the expression, functional role, and prognostic value of PLEKHA4 in glioma.MethodsThe expression levels of PLEKHA4 in 33 types of cancer in the TCGA (The Cancer Genome Atlas) database were collected via the UCSC Xena browser. The clinical samples of glioma patients were downloaded from the TCGA database. Immunohistochemistry was used to verify PLEKHA4 expression in tumor tissues. We assessed the influence of PLEKHA4 on survival of glioma patients by survival module and GEPIA. Then, we downloaded datasets of glioma from TCGA and investigated the correlations between the clinical characteristics and PLEKHA4 expression using logistic regression. Moreover, we used TIMER to explore the collection of PLEKHA4 expression and immune infiltration level in glioma and to analyze cumulative survival in glioma. Gene Set Enrichment Analysis (GSEA) was performed using the TCGA dataset.ResultsPLEKHA4 transcript levels were significantly upregulated in multiple cancer types, including gliomas. Moreover, immunohistochemical analysis verified that PLEKHA4 was overexpressed in gliomas compare to the corresponding normal tissues. Univariable survival and multivariate cox analysis show that increased PLEKHA4 expression significantly correlated with age, tumor grade, IDH mutation status, and 1p/19q codel status, and higher PLEKHA4 had shorter OS, DSS, and PFI. Specifically, PLEKHA4 expression level had significant positive correlations with infiltrating levels of B cell, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and DCs in glioma, and upregulation of PLEKHA4 expression was significantly related to immune cell biomarkers and immune checkpoint expression in glioma. In addition, several GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) items associated with immune response, JAK STAT signal pathway, and cell cycle were significantly enriched in the high PLEKHA4 expression phenotype pathway.ConclusionsOur findings proposed that PLEKHA4 was an independent prognostic biomarker and correlated with immune infiltrates in glioma, and targeting PLEKHA4 might improve immunotherapy in glioma. Of course, these findings also need basic experiments and further clinical trials to confirm in the future.
| S-EPMC9881441 | biostudies-literature
Project description:Background: Glioma is globally recognised as one of the most frequently occurring primary malignant brain tumours, making the identification of glioma biomarkers critically significant. The protein KIF18A (Kinesin Family Member 18A) is a member of the kinesin superfamily of microtubule-associated molecular motors and has been shown to participate in cell cycle and mitotic metaphase and anaphase. This is the first investigation into the expression of KIF18A and its prognostic value, potential biological functions, and effects on the immune system and mitosis in glioma patients. Methods: Gene expression and clinicopathological analysis, enrichment analysis, and immune infiltration analysis were based on data obtained from The Cancer Genome Atlas (TCGA), with additional bioinformatics analyses performed. Statistical analysis was conducted in R software. Clinical samples were used to evaluate the expression of KIF18A via immunohistochemical staining. In addition, the expression level of KIF18A was validated on U87 cell line. Results: Our results highlighted that KIF18A plays a key role as an independent prognostic factor in patients with glioma. KIF18A was highly expressed in glioma tissues, and KIF18A expression was associated with age, World Health Organization grade, isocitrate dehydrogenase (IDH) status, 1p/19q codeletion, primary therapy outcome, and overall survival (OS). Enrichment analysis revealed that KIF18A is closely correlated with the cell cycle and mitosis. Single sample gene set enrichment analysis (ssGSEA) analysis revealed that KIF18A expression was related to the immune microenvironment. The increased expression of KIF18A in glioma was verified in clinical samples and U87 cell line. Conclusion: The identification of KIF18A as a new biomarker for glioma could help elucidate how changes in the glioma cell and immune microenvironment promote glioma malignancy. With further analysis, KIF18A may serve as an independent prognostic indicator for human glioma.
| S-EPMC9110815 | biostudies-literature
Project description:Hepatocellular carcinoma is a malignant type of carcinoma with complicated pathogenesis. For HCC patients, there is not only a lack of valuable therapeutic targets, but also a lack of prognostic biomarker. The protein encoded by Aldehyde Dehydrogenase 2 Family Member (ALDH2) is a critical member of the aldehyde dehydrogenase family. Many researchers have found that ALDH2 mutations play an important role in the activation of hepatocellular carcinoma carcinogenic pathways. However, the clinicopathological meaning of ALDH2 in HCC and its relation with immune infiltration is still indistinguishable. In this study, we explored the expression of ALDH2 in 41 HCC tissues by immunohistochemistry. The clinicopathological meaning and molecular function of ALDH2 were analyzed and evaluated through comprehensive bioinformatics. ALDH2 expression in HCC was validated in TCGA, GEO and Oncomine databases, and a survival of ALDH2 based on TCGA database was analysed. LinkedOmics was used to classify the co-expressed genes of ALDH2 and its regulatory factors. The relation between ALDH2 and immune infiltration in HCC was further explored by TIMER. IHC results showed decreased levels of ALDH2 in HCC tumor tissues compared with corresponding normal liver tissues. The pathological grade and prognosis of patients with low expression of the ALDH2 gene were worse. Bioinformatics analysis results showed that ALDH2 was considerably down-regulated in cancer tissues compared with corresponding normal liver tissues in 8 GEO series and TCGA profile (all P<0.05). A nomogram was designed using expression of ALDH2 and clinical factors. ALDH2 was correlated with dendritic cells and macrophages in immune infiltration. In conclusion, ALDH2 has significant prognostic value in hepatocellular carcinoma and they may play key roles in regulating tumor progression and the immune cells infiltration. Our results suggest that ALDH2 may be a new type of tumor biomarker, which can be used to judge the prognosis, targeted therapy and immunotherapy of patients with HCC.
| S-EPMC8640816 | biostudies-literature
Project description:Glioma is the common, most aggressive and poorest prognostic tumor type in the brain. More and more biomarkers associated with glioma treatment, prognosis, and immunity are being discovered. Here, we aimed to explore the underlying biological functions and prognostic predictive value of Apolipoprotein L4 (APOL4) in glioma. We downloaded the expression data of APOL4 and clinical information from several databases and used R software for preprocessing. The clinical significance of APOL4 in a glioma outcome was explored by the Cox regression analysis and Kaplan-Meier survival analysis. In addition, immune infiltrates and microenvironmental indicators were assessed by CIBERSORT and TIMER. GO and KEGG analyses were used to analyze the potential functions of APOL4 in gliomas. APOL4 expression was increased in glioma specimens compared to normal tissues and correlated dramatically with the WHO grade. A survival analysis showed a shorter overall survival (OS) in glioma patients with APOL4 overexpression, and a Cox regression analysis showed that APOL4 was an independent prognostic factor for the OS of glioma patients. GSEA, GO, and KEGG enrichment analyses showed remarkable enrichment in immune-related pathways. APOL4 expression was positively correlated with immune infiltration (including DC cells, neutrophils, CD8+ T cells, B cells, macrophages, CD4+ T cells, etc.) and microenvironmental parameters (including immune, stromal, and ESTIMATE scores) in gliomas. Glioma patients with a higher expression of APOL4 may be more sensitive to immune checkpoint inhibitors (ICI). In conclusion, these findings suggest that APOL4 is associated with the tumor grade and immune infiltrates; APOL4 may be a new and potential biomarker for therapeutic and prognostic evaluations that may further suggest the therapeutic efficacy of immunotherapy.
| S-EPMC9572388 | biostudies-literature
Project description:Background The prognosis is poor for hepatocellular carcinoma (HCC), a tumor and cancer associated with inflammation that is common. New data showed that significant levels of KIAA1522 were expressed in HCC tissues and cell lines, suggesting that KIAA1522 may be a highly useful prognostic marker for HCC. However, its biochemical processes and impacts on the immune system go deeper. Objective To verify the significance of KIAA1522 in HCC and investigate its related carcinogenic mechanisms. Methods Studies examining the relationship between KIAA1522 expression and clinical-pathologic characteristics in HCC have been checked in the Cancer Genome Atlas (TCGA) database. A receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of KIAA1522 in HCC. Western blot analysis was used to find the presence of the KIAA1522 protein in the tumor and paraneoplastic tissues of eight randomly chosen HCC patients. The GSVA program in R language was used to evaluate the relationship between KIAA1522 and immune cell infiltration in HCC. We searched the Search Tool for the Retrieval of Interacting Genes (STRING) database for interacting proteins connected to the expression of KIAA1522. Pathways were involved in the enrichment analysis of KIAA1522 to anticipate potential mechanisms through which KIAA1522 may affect immunological infiltration. Results Our study found that KIAA1522 was commonly elevated in HCC tumor tissues and that it also signaled a bad outcome. We found an inverse link between KIAA1522 and cytotoxic cells and an inverse relationship between KIAA1522 and Th2 cell infiltration. In STRING analysis, the top 5 coexpressed proteins of KIAA1522 were BAIAP2, NCK2, TSNAXIP1, POGK, and KLHL31. The effect of KIAA1522 on HCC may entail cell cycle alteration, an immunological response, and suppression of the PPAR signaling pathway. Conclusion High expression of KIAA1522 was linked to HCC immune cell infiltration, disease progression, and a poor prognosis.
| S-EPMC9904920 | biostudies-literature
Project description:BackgroundGlioma is one of the most common malignancies in the central nervous system and has limited effective therapeutic options. Therefore, we sought to identify a suitable target for immunotherapy.Materials and methodsWe screened prognostic genes for glioma in the CGGA database and GSE43378 dataset using survival analysis, receiver operating characteristic (ROC) curves, independent prognostic analysis, and clinical correlation analysis. The results were intersected with immune genes from the ImmPort database through Venn diagrams to obtain likely target genes. The target genes were validated as prognostically relevant immune genes for glioma using survival, ROC curve, independent prognostic, and clinical correlation analyses in samples from the CGGA database and GSE43378 dataset, respectively. We also constructed a nomogram using statistically significant glioma prognostic factors in the CGGA samples and verified their sensitivity and specificity with ROC curves. The functions, pathways, and co-expression-related genes for the glioma target genes were assessed using PPI networks, enrichment analysis, and correlation analysis. The correlation between target gene expression and immune cell infiltration in glioma and the relationship with the survival of glioma patients were investigated using the TIMER database. Finally, target gene expression in normal brain, low-grade glioma, and high-grade glioma tissues was detected using immunohistochemical staining.ResultsWe identified TNFRSF12A as the target gene. Satisfactory results from survival, ROC curve, independent prognosis, and clinical correlation analyses in the CGGA and GSE43378 samples verified that TNFRSF12A was significantly associated with the prognosis of glioma patients. A nomogram was constructed using glioma prognostic correlates, including TNFRSF12A expression, primary-recurrent-secondary (PRS) type, grade, age, chemotherapy, IDH mutation, and 1p19q co-deletion in CGGA samples with an AUC value of 0.860, which illustrated the accuracy of the prognosis prediction. The results of the TIMER analysis validated the significant correlation of TNFRSF12A with immune cell infiltration and glioma survival. The immunohistochemical staining results verified the progressive up-regulation of TNFRSF12A expression in normal brain, low-grade glioma, and high-grade glioma tissues.ConclusionWe concluded that TNFRSF12A was a viable prognostic biomarker and a potential immunotherapeutic target for glioma.
| S-EPMC8085360 | biostudies-literature
Project description:Background: ADPRH is a modulator of CD8+ T cell functions, and dysregulation of ADPRH has been identified to involve in carcinogenesis of cancers. However, the association of ADPRH with low grade glioma (LGG) remains unclear. Methods: The expression of ADPRH in LGG was first analyzed in GLIOVIS and GEPIA databases and then validated by real-time PCR (rt-PCR), immunochemistry and human protein atlas (HPA). Univariate and multivariate Cox analysis and Kaplan-Meier plots were designed to assess the prognostic value of ADPRH in LGG. The correlation of ADPRH and immune infiltration was evaluated by data in TIMER and ESTIMATE databases. Gene set enrichment analysis was conducted to detect biological processes associated with ADPRH. Results: ADPRH was significantly upregulated in LGG in comparison to non-tumor brain samples in transcriptomic and proteomic levels. The high ADPRH expression indicated unfavorable overall survival (OS) and progression-free survival (PFS) in patients with LGG using Kaplan-Meier plots. And multivariate Cox analysis demonstrated the expression level of ADPRH was an independent prognosis-predicting index for OS and PFS of LGG patients in all cohorts separately. Gene Set Enrichment Analysis (GSEA) indicated that high expression of ADPRH was involved in the upregulation of P53 signaling pathway, KRAS signaling pathway, IL6/JAK-STAT3 signaling and TNF-beta signaling pathways. By TIMER and ESTIMATE databases, we identified ADPRH expression had strong correlation with tumor immune infiltrating cells (TIICs). Conclusions: In summary, our findings demonstrated that ADPRH might be a potential prognostic biomarker and correlated with TIICs in LGG.
| S-EPMC8040889 | biostudies-literature
Project description:BackgroundRunt-related transcription factor 1 (RUNX1) is a vital regulator of mammalian expression. Despite multiple pieces of evidence indicating that dysregulation of RUNX1 is a common phenomenon in human cancers, there is no evidence from pan-cancer analysis.MethodsWe comprehensively investigated the effect of RUNX1 expression on tumor prognosis across human malignancies by analyzing multiple cancer-related databases, including Gent2, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), the Human Protein Atlas (HPA), UALCAN, PrognoScan, cBioPortal, STRING, and Metascape.ResultsBioinformatics data indicated that RUNX1 was overexpressed in most of these human malignancies and was significantly associated with the prognosis of patients with cancer. Immunohistochemical results showed that most cancer tissues were moderately positive for granular cytoplasm, and RUNX1 was expressed at a medium level in four types of tumors, including cervical cancer, colorectal cancer, glioma, and renal cancer. RUNX1 expression was positively correlated with infiltrating levels of cancer-associated fibroblasts (CAFs) in 33 different cancers. Moreover, RUNX1 expression may influence patient prognosis by activating oncogenic signaling pathways in human cancers.ConclusionOur findings suggest that RUNX1 expression correlates with patient outcomes and immune infiltrate levels of CAFs in multiple tumors. Additionally, the increased level of RUNX1 was linked to the activation of oncogenic signaling pathways in human cancers, suggesting a potential role of RUNX1 among cancer therapeutic targets. These findings suggest that RUNX1 can function as a potential prognostic biomarker and reflect the levels of immune infiltrates of CAFs in human cancers.
| S-EPMC9088136 | biostudies-literature