Abnormally high expression of HOXA2 as an independent factor for poor prognosis in glioma patients.
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ABSTRACT:
SUBMITTER: Liu Z
PROVIDER: S-EPMC7469623 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundXRCC2, a homologous recombination-related gene, has been reported to be associated with a variety of cancers. However, its role in glioma has not been reported. This study aimed to find out the role of XRCC2 in glioma and reveal in which glioma-specific biological processes is XRCC2 involved based on thousands of glioma samples, thereby, providing a new perspective in the treatment and prognostic evaluation of glioma.MethodsThe expression characteristics of XRCC2 in thousands of glioma samples from CGGA and TCGA databases were comprehensively analyzed. Wilcox or Kruskal test was used to analyze the expression pattern of XRCC2 in gliomas with different clinical and molecular features. The effect of XRCC2 on the prognosis of glioma patients was explored by Kaplan-Meier and Cox regression. Gene set enrichment analysis (GSEA) revealed the possible cellular mechanisms involved in XRCC2 in glioma. Connectivity map (CMap) was used to screen small molecule drugs targeting XRCC2 and the expression levels of XRCC2 were verified in glioma cells and tissues by RT-qPCR and immunohistochemical staining.ResultsWe found the overexpression of XRCC2 in glioma. Moreover, the overexpressed XRCC2 was associated with a variety of clinical features related to prognosis. Cox and meta-analyses showed that XRCC2 is an independent risk factor for the poor prognosis of glioma. Furthermore, the results of GSEA indicated that overexpressed XRCC2 could promote malignant progression through involved signaling pathways, such as in the cell cycle. Finally, doxazosin, quinostatin, canavanine, and chrysin were identified to exert anti-glioma effects by targeting XRCC2.ConclusionsThis study analyzed the expression pattern of XRCC2 in gliomas and its relationship with prognosis using multiple datasets. This is the first study to show that XRCC2, a novel oncogene, is significantly overexpressed in glioma and can lead to poor prognosis in glioma patients. XRCC2 could serve as a new biomarker for glioma diagnosis, treatment, and prognosis evaluation, thus bringing new insight into the management of glioma.
| S-EPMC8164800 | biostudies-literature
Project description:Glioma is the most common and fatal primary brain tumor in humans. Myosin binding protein H (MYBPH), which was first identified as an important myofibrillar constituent of vertebrate skeletal and cardiac muscles, reduces cell motility and metastasis. However, its role in gliomas remains unclear. We evaluated the expression of MYBPH in glioma using Gene Expression Profiling Interactive Analysis ( http://gepia.cancer-pku.cn/ ) and Chinese Glioma Genome Atlas ( https://www.cgga.org.cn/ ). The results showed that MYBPH was highly expressed in glioma tissues. Moreover, MYBPH expression was significantly associated with high tumor aggressiveness and poor outcomes in glioma patients. Mechanistically, the results suggested that MYBPH might promote tumor progression by improving tumor invasion and migration. Our results establish MYBPH as an important prognostic biomarker that could be considered a potential epigenetic and immunotherapeutic target for treatment. We showed that MYBPH is a novel biomarker that is variably expressed in glioblastoma (GBM). The association of high MYBPH expression with poor prognosis in newly diagnosed GBM patients and increased expression in recurrent GBM is indicative of its role in tumor aggressiveness.
| S-EPMC8795254 | biostudies-literature
Project description:Ribonucleotide reductase subunit M2 may play a role as a potential prognostic biomarker in several cancers. In this study, we evaluated whether RRM2 gene expression is associated with the prognosis of patients with lung adenocarcinoma (LUAD) using publicly available data from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test and logistic regression were performed to evaluate the association between RRM2 expression and clinical features in patients with LUAD. Kaplan-Meier and Cox regression methods were used to examine the effect of RRM2 expression level in the overall survival, and a nomogram was performed to illustrate the correlation between the RRM2 gene expression and the risk of LUAD. TCGA data set was used for gene set enrichment analysis (GSEA). We also performed a further experiment in vitro to assess the effect of RRM2 expression on the proliferation and invasive abilities of LUAD cells and its key signaling pathway proteins. Our results revealed that the expression level of RRM2 in patients with LUAD was much higher than that in normal tissues (p = 3.99e-32). High expression of RRM2 was significantly associated with tumor stage (IV vs. I: OR = 3.02, p = 0.012) and TNM classification (T2 vs. T1: OR = 1.88, p = 0.001; N2 vs. N0: OR = 2.69, p < 0.001). Kaplan-Meier survival analysis showed that high expression of RRM2 was associated with a worse prognosis of LUAD compared low expression of RRM2 (p = 7.86e-04). Multivariate analysis showed that high RRM2 expression was an independent factor affecting overall survival (HR = 1.29, p < 0.001). The association between RRM2 gene expression and the risk of LUAD was presented in a nomogram. GSEA revealed that the cell cycle, p53 signaling pathway, DNA replication, small cell lung cancer, apoptosis, and pathways in cancer were differentially enriched in patients with high expression of RRM2. RRM2 over-expression promoted the proliferation and invasive abilities of LUAD cells. RRM2 over-expression increased the activation of Bcl-2 and E-cadherin signaling pathways, and reduced the activation of p53 signaling pathway. In summary, high RRM2 expression is an independent predictive factor of poor prognosis in patients with lung adenocarcinoma.
| S-EPMC7906179 | biostudies-literature
Project description:Purpose: Glioma is the most common malignant brain tumor. The molecular mechanisms underlying its malignancy are not fully understood. LAMC1, which encodes extracellular matrix protein laminin ?1, has been implicated in some malignant tumors but has not been systematically evaluated in glioma. The aim of this study was to evaluate the expression of LAMC1 and its clinical significance. Patients and methods: LAMC1 protein expression in 52 fresh-frozen specimens of different pathological grade gliomas and 5 normal brain tissues was detected by Western blotting. Immunohistochemistry was used to detect LAMC1 protein expression in another set of 76 glioma tissues and 8 normal brain tissues. The associations between clinicopathological factors and LAMC1 expression were analyzed. A log-rank test and a multivariate Cox proportional hazards model were used to determine the relationship between LAMC1 expression and patient prognosis. The expression of LAMC1 at the mRNA level was analyzed in the TCGA database. Results: LAMC1 was highly expressed in high-grade glioma tissues, with moderate expression in low-grade gliomas, and weak or no expression in normal brain tissues, as detected by Western blotting and immunohistochemistry. A chi-square test indicated that LAMC1 expression was associated with pathological grade but not with other clinicopathological factors, such as age, sex, and tumor size. LAMC1 expression at the mRNA level was upregulated in high-grade gliomas compared with low-grade gliomas and normal brain tissue in the TCGA database. The Kaplan-Meier plot and log-rank test in our patient series showed that high LAMC1 expression was significantly associated with shorter survival, which was consistent with the TCGA database analysis. A multivariate Cox proportional hazards model revealed that LAMC1 expression, WHO grade, and surgery procedure were significantly correlated with overall survival and progression-free survival. Conclusion: These results demonstrated that LAMC1 may play an important role in glioma progression and may be used in the diagnosis, prognosis, and targeted therapy of glioma patients.
| S-EPMC6549796 | biostudies-literature
Project description:BackgroundThe carcinogenic effect of NUP37 has been reported recently in a variety of tumors, but its research in the field of glioma has not been paid attention. The main purpose of this study is to reveal the relationship between NUP37 and prognosis or clinical characteristics of glioma patients.MethodsFirst, as a retrospective study, this study included thousands of tissue samples based on a variety of public databases and clinicopathological tissues. Second, a series of bioinformatics analysis methods were used to analyze the NUP37 and glioma samples from multiple databases such as the CGGA, TCGA, GEO, HPA, and GEPIA. Third, to analyze the relationship between the expression level of NUP37 in tumor tissues and cells and a variety of clinical prognostic molecular characteristics, whether it can be an independent risk factor leading to poor prognosis in glioma and whether it has clinical diagnostic value; GSEA was used to analyze the cancer-related signaling pathways that may be activated by high expression of NUP37. Fifth, CMap was used to analyze small molecule drugs that may inhibit NUP37 expression. Finally, the meta-analysis of thousands of tissue samples from seven datasets and cell proliferation and migration experiments confirmed that NUP37 has a malignant effect on glioma.ResultsNUP37 is highly expressed in glioma patient tissues and glioma cells, significantly correlates with reduced overall survival, and may serve as an independent prognostic factor with some diagnostic value. Silencing NUP37 suppresses malignant biological behaviors of glioma cells. 4 small molecule drugs that had potential targeting inhibitory effects on NUP37 overexpression.ConclusionsThis study demonstrates for the first time a malignant role of NUP37 in glioma and provides a vision to unravel the complex pathological mechanisms of glioma and a potentially valuable biomarker for implementing individualized diagnosis and treatment of glioma.
| S-EPMC8335818 | biostudies-literature
Project description:Gliomas are the most common primary brain tumors. Because of their high degree of malignancy, patient survival rates are unsatisfactory. Therefore, exploring glioma biomarkers will play a key role in early diagnosis, guiding treatment, and monitoring the prognosis of gliomas. We found two lncRNAs, six miRNAs, and nine mRNAs that were differentially expressed by analyzing genomic data of glioma patients. The diagnostic value of mRNA expression levels in gliomas was determined by receiver operating characteristic (ROC) curve analysis. Among the nine mRNAs, the area under the ROC curve values of only CEP55 and SHCBP1 were >0.7, specifically 0.834 and 0.816, respectively. Additionally, CEP55 and SHCBP1 were highly expressed in glioma specimens and showed increased expression according to the glioma grade, and outcomes of high expression patients were poor. CEP55 was enriched in the cell cycle, DNA replication, mismatch repair, and P53 signaling pathway. SHCBP1 was enriched in the cell cycle, DNA replication, ECM receptor interaction, and P53 signaling pathway. Age, grade, IDH status, chromosome 19/20 cogain, and SHCBP1 were independent factors for prognosis. Our findings suggest the PART1-hsa-miR-429-SHCBP1 regulatory network plays an important role in gliomas.
| S-EPMC7174919 | biostudies-literature
Project description:BackgroundGlioma 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.MethodsThe 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.ResultsCD276 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.ConclusionsThe present study demonstrated that high expression of CD276 in gliomas indicates a poor prognosis.
| S-EPMC8299877 | biostudies-literature
Project description:Osteosarcoma (OS) is the most prevalent malignant bone tumor in children and young adults. There is an urgent need for a novel biomarker related to the prognosis of OS. We performed a meta-analysis incorporating six independent datasets and performed a survival analysis with one independent dataset GSE21257 in the GEO database for gene screening. The results revealed that one potential biomarker related to OS survival, POGZ was the most significantly upregulated gene. We also verified that the POGZ was overexpressed in clinical samples. The survival analysis revealed that POGZ is associated with a poor prognosis in OS. Moreover, flow cytometry analysis of isolated OS cells demonstrated that OS cells were arrested in the G1 phase after POGZ knockdown. The RNA-seq results indicated that POGZ was co-expressed with CCNE1 and CCNB1. Pathway analysis showed that genes associated with high expression levels of POGZ were related to the cell cycle pathway. A cell model was constructed to detect the effects of POGZ. After POGZ knockdown, OS cell proliferation, invasion and migration were all decreased. Therefore, POGZ is an important gene for evaluating the prognosis of OS patients and is a potential therapeutic target.
| S-EPMC8431870 | biostudies-literature
Project description:Eukaryotic initiation factor 3 subunit M (EIF3M) is required for key steps in the initiation of protein synthesis, and dysregulation of EIF3M is associated with tumorigenesis. This study aimed to explore the clinicopathological and prognostic role of EIF3M in patients with colon adenocarcinoma. A total of 82 pathology specimens, 20 freeze-thawed tumors and 80 healthy controls were used to investigate the expression of EIF3M in colon adenocarcinoma through immunohistochemistry, western blotting, RT-qPCR and ELISA. In addition, Kaplan-Meier curves and Cox regression analysis were used to analyze overall survival (OS) and disease-free survival (DFS). Furthermore, the Oncomine database was used for analyzing EIF3M expression. The positive rate of EIF3M in colon adenocarcinoma was higher compared with that in normal colon tissues (62.20% vs. 29.27%; P<0.001). The mean score of EIF3M was also higher in colon adenocarcinoma compared with normal colon tissue (17.28±10.05 vs. 6.53±4.87; P<0.001). The levels of EIF3M expression in freeze-thawed tumors and serum from 20 patients with colon adenocarcinoma were higher than those in normal tissues and serum from healthy controls, respectively (P<0.001). In addition, positive expression of EIF3M was associated with tumor size (P=0.002) and Dukes' stage (P<0.001). In multivariate Cox regression analysis, EIF3M expression was an independent prognostic factor for OS (P=0.003) and DFS (P=0.001). Oncomine database analysis showed a higher expression of EIF3M expression in colon adenocarcinoma compared with normal colon tissues, colon squamous cell carcinomas or gastrointestinal stromal tumors. In conclusion, EIF3M expression was associated with tumor size and Dukes' stage in colon adenocarcinoma. Hence, EIF3M is a potential prognostic indicator for colon adenocarcinoma.
| S-EPMC6924177 | biostudies-literature
Project description:Background and Aims:In patients with nasopharyngeal carcinoma (NPC), local treatment failure and distant metastasis contribute largely to poor outcomes. The nasopharynx is an important lymphoid tissue, and NPC tumourigenesis and development are partly attributed to immune system disorders. Human leukocyte antigen F (HLA-F) has shown a close correlation with NPC in many genome-wide association studies (GWASs). However, clinical studies rarely explore the relationship of HLA-F expression with the clinical parameters and outcomes in patients with NPC. Methods:In this study, we used immunohistochemistry to evaluate HLA-F expression in 74 paraffin-embedded NPC tissue sections and then analysed the association between HLA-F expression and clinical parameters and outcomes. The plasma concentration of soluble HLA-F (sHLA-F) in NPC patients and normal controls was also detected, via enzyme-linked immunosorbent assay (ELISA). Results:Low, moderate, and high HLA-F expression levels were observed in 47.3% (35/74), 35.1% (26/74), and 17.6% (13/74), respectively, of the tissue samples. HLA-F expression showed a significant correlation with local recurrence (p = 0.037) and distant metastasis (p = 0.024) and was also an independent factor for local recurrence-free survival (LRFS; p = 0.016) and distant metastasis-free survival (DMFS; p = 0.004). Although the mean concentration of plasma sHLA-F in the NPC patients was higher than that in the normal controls (13.63?pg/ml vs. 10.06?pg/ml), no statistical significance was observed (p = 0.118). Conclusions:Our study provides the first evidence that high HLA-F expression is associated with NPC local recurrence and distant metastasis and may be regarded as a poor prognostic factor for NPC patients. Additional studies using larger sample sizes may be necessary to determine whether sHLA-F is a feasible NPC diagnostic indicator.
| S-EPMC6232804 | biostudies-literature