High expression of PSMC2 promotes gallbladder cancer through regulation of GNG4 and predicts poor prognosis.
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ABSTRACT:
SUBMITTER: Zhu D
PROVIDER: S-EPMC8138011 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:DHCR7 is a rate-limiting enzyme in cholesterol synthesis. The expression pattern and prognostic value of DHCR7 in cervical cancer are unknown. We investigated the relationship between DHCR7 expression and clinicopathological features of cervical cancer patients. The dataset was acquired from TCGA database. The Wilcoxon rank sum test was used to explore DHCR7 expression level in cervical cancer. The Kruskal-Wallis test and the logistic regression were performed to estimate the association between the DHCR7 and clinical features. The Kaplan-Meier and Cox regression analyses were used to evaluate factors that affect cervical cancer prognosis. GSEA was used to screen the DHCR7-related pathways. We found that DHCR7 was increased in cervical cancer samples and increased DHCR7 was correlated with advanced T stage, lymph node invasion, and clinical stage (P < 0.05). Patients with elevated DHCR7 levels had poorer overall survival (P = 0.021), progression-free interval (P = 0.002), and disease-specific survival (P = 0.005). Cox analysis revealed that DHCR7 was an independent prognostic factor in cervical cancer (P = 0.005). WNT activated receptor activity, G2/M checkpoint, mTORC1 signaling, KRAS signaling, regulation of cholesterol biosynthetic, FGF signaling, T-cell receptor signaling, JAK/STAT signaling cascade T cell activation, and macrophage migration were enriched in high DHCR7 phenotype. Our data also showed that DHCR7 moderately correlates with T-cell infiltration, including CD8+ T-cells. Conclusion. Increased DHCR7 expression is associated with poor survival in cervical cancer.
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Project description:Background: PYGL has been reported as a glycogen degradation-related gene, which is up-regulated in many tumors. This study was designed to investigate the predictive value of high PYGL expression in patients with gliomas through bioinformatics analysis of the gene transcriptome and the single-cell sequencing data. Methods: The gene transcriptome data of 595 glioma patients from the TCGA database and the single-cell RNA sequencing data of 7,930 GBM cells from the GEO database were included in the study. Differential analysis was used to find the distribution of expression of PYGL in different groups of glioma patients. OS analysis was used to assess the influence of the high expression of PYGL on the prognosis of patients. The reliability of its prediction was evaluated by the AUC of ROC and the C-index. The GSEA be used to reveal potential mechanisms. The single-cell analysis was used to observe the high expression of PYGL in different cell groups to further analyze the mechanism of its prediction. Results: Differential analysis identified the expression level of PYGL is positively associated with glioma malignancy. OS analysis and Cox regression analyses showed high expression of PYGL was an independent factor for poor prognosis of gliomas (p < 0.05). The AUC values were 0.838 (1-year ROC), 0.864 (3-year ROC) and 0.833 (5-year ROC). The C index was 0.81. The GSEA showed that gene sets related to MTORC1 signaling, glycolysis, hypoxia, PI3K/AKT/mTOR signaling, KRAS signaling up and angiogenesis were differentially enriched in the high PYGL expression phenotype. The single-cell sequencing data analysis showed TAMs and malignant cells in GBM tissues expressed a high level of PYGL. Conclusion: The high expression of PYGL is an independent predictor of poor prognosis in patients with glioma.
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Project description:Semaphorin 4C (SEMA4C), is an important regulator of axonal guidance and aggravates tumor development. However, the roles and prognostic value of SEMA4C in colorectal cancer (CRC) remain unclear. Here, bioinformatics analyses of transcriptome data from multiple CRC patient datasets and immunohistochemical staining of a CRC tissue microarray (TMA) (n=83) showed that SEMA4C mRNA and protein expression were higher in CRC tissues than normal colorectal tissues. SEMA4C mRNA and protein expression correlated with pathologic stage and metastasis in CRC patients. Higher SEMA4C expression was associated with shorter overall survival, consensus molecular subtype 4 (CMS4), and DNA hypomethylation of SEMA4C in CRC patients. Multivariate Cox regression analyses revealed that SEMA4C expression was an independent prognostic predictor in CRC patients. Gene set expression analysis (GSEA) illustrated that SEMA4C expression had remarkable correlations with epithelial-mesenchymal transition (EMT) as well as hedgehog, Wnt/β-catenin, TGF-β, and Notch signaling pathways. Receiver operating characteristic (ROC) curve analysis demonstrated that SEMA4C expression accurately distinguished between the CMS4 and CMS1-3 subtypes of CRC patients. By inhibiting EMT, SEMA4C silencing reduced in vitro proliferation, migration, and invasion by CRC cells. These findings suggest that SEMA4C is a CMS4-associated gene that enhances CRC progression by inducing EMT.
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