High RPS27A Expression Predicts Poor Prognosis in Patients With HPV Type 16 Cervical Cancer
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ABSTRACT:
SUBMITTER: Wang Q
PROVIDER: S-EPMC8593198 | 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:BackgroundEzrin, a member of the ezrin/radixin/moesin (ERM) protein family, plays a pivotal role in tumor invasion and metastasis. This study is aimed to investigate the clinicopathological significance of upregulated ezrin protein expression in uterine cervical cancers.MethodsImmunohistochemical staining of ezrin protein was performed on uterine cervical cancer specimens from 235 patients. For comparison, 239 cases of cervical intraepithelial neoplasia (CIN), 17 cases of cervical glandular intraepithelial neoplasia (CGIN) and 52 normal cervix samples were also included. qRT-PCR was performed on fresh tissues to detect ezrin mRNA expression levels. HPV infection statuses were genotyped by oligonucleotide microarray, and 10-year survival rates were calculated using the Kaplan-Meier method for 109 cervical cancer patients.ResultsApical membranous distribution of ezrin protein was only observed in normal cervical glands, while perinuclear staining was only observed in cervical cancers. Strong cytoplasmic and diffuse localization of ezrin were frequently seen in the cervical cancers compared with the normal counterparts. Furthermore, this strongly positive ezrin expression was significantly higher in cervical cancers than in CIN, CGIN, and normal cervical epithelia. Ezrin overexpression was closely related with poor differentiation, late stage, and lymph node metastasis. Additionally, ezrin overexpression was associated with lower 10-year survival rate for patients with early stage cervical cancer, but not for patients with advanced stage.ConclusionsAberrant localization and overexpression of ezrin might be an independent effective biomarker for prognostic evaluation of cervical cancers.
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Project description:Background: The prognosis of patients with advanced cervical cancer remains unsatisfactory. A study indicated that transmembrane protein 33 (TMEM33) was implicated in tumor recurrence, while its role in cervical cancer has not been elucidated. Methods: TMEM33 expression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) was primarily screened in The Cancer Genome Atlas (TCGA), and further validated in Gene Expression Omnibus (GEO) database. The Kaplan-Meier plotter analysis and Cox regression were constructed to evaluate the prognostic value of TMEM33 in CESC. Functional enrichment analysis was performed with GO, KEGG and GSEA tools. CCK-8 assay and colony formation assay were performed to investigate the carcinogenesis role of TMEM33 in cervical cancer cell proliferation. Results: TMEM33 expression was significantly elevated in CESC compared with normal tissues. High expression of TMEM33 was associated with poor prognostic clinical characteristics in CESC patients. KM-plotter analysis revealed that patients with increased TMEM33 had shorter overall survival (OS), progress free interval (PFI), and disease specific survival (DSS). Moreover, Multivariate Cox analysis confirmed that high TMEM33 expression was an independent risk factor for OS in patients with CESC. TMEM33 was associated with immune infiltrates, and its expression was correlated with tumorigenesis-related genes RNF4, OCIAD1, TMED5, DHX15, MED28 and LETM1. More importantly, knockdown of TMEM33 in cervical cancer cells decreased the expression of those genes and inhibited cell proliferation. Conclusion: Increased TMEM33 in cervical cancer can serve as an independent prognostic marker and might play a role in tumorigenesis by promoting cell proliferation.
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Project description:Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.
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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:Apelin (APLN) is an endogenous ligand of the G protein-coupled receptor APJ (APLNR). APLN/APLNR system was involved in a variety of pathological and physiological functions, such as tumorigenesis and development. However, its prognostic roles in patients with central nervous system (CNS) cancers remain unknown. The present study was designed to explore the expression profile, prognostic significance, and interaction network of APLN/APLNR by integrating data from Oncomine, GEPIA, LOGpc, STRING, GeneMANIA, and immunohistochemical staining. The results demonstrated that APLN and APLNR mRNA expression were significantly increased in CNS cancers, including both low-grade glioma (LGG) and glioblastoma (GBM), when compared with normal CNS tissues. The high APLN, but not APLNR, expression was significantly correlated with overall survival (OS), recurrence free survival (RFS), and progression free survival (PFS) of LGG patients. However, neither APLN nor APLNR expression was significantly related to prognostic value in terms of OS, disease free interval (DFI), disease specific survival (DSS), or progression free interval (PFI) for GBM patients. Additionally, immunohistochemistry staining confirmed the increased APLN expression in tissues of LGG patients with grade II than grade I. These results showed that an elevated APLN level could predict poor OS, RFS, and PFS for LGG patients, and it could be a promising prognostic biomarker for LGG.
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Project description:Hepsin, a membrane-associated serine protease, is frequently upregulated in epithelial cancers and involved in cancer progression. Our study aims to describe the expression pattern and evaluate the clinical implication of hepsin in gastric cancer patients. The mRNA expression of hepsin was analyzed in 50 gastric cancer and matched non-tumor tissues, which was downregulated in 78% (39/50) of gastric cancer. By searching and analyzing four independent datasets from Oncomine, we obtained the similar results. Furthermore, we evaluated the hepsin expression by IHC in tissue microarray (TMA) containing 220 Gastric Cancer specimens. More importantly, Kaplan-Meier survival and Cox regression analyses were taken to access the prognosis of gastric cancer and predicted that hepsin protein expression was one of the significant and independent prognostic factors for overall survival of Gastric Cancer.
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Project description:Cervical cancer has the second-highest incidence and mortality of female malignancy. The major causes of mortality in patients with cervical cancer are invasion and metastasis. The epithelial-mesenchymal transition (EMT) process plays a major role in the acquisition of metastatic potential and motility. Autophagy-related genes (ARGs) are implicated in the EMT process, and autophagy exerts a dual function in EMT management at different phases of tumor progression. However, the role of specific ARGs during the EMT process has not yet been reported in cervical cancer. Based on the data from the Cancer Genome Atlas (TCGA) cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) sequencing database, we performed the prognosis analysis for those ARGs obtained from the Human Autophagy database. ATG5 was identified as the only important harmful marker influencing survival of cervical cancer patients by univariate Cox regression (HR 1.7; 95% CI: 1.0-2.8, p = 0.047), and the 5-years survival rate for the high- and low-ATG5 expression groups was 0.486 (0.375-0.631) and 0.782 (0.708-0.863), respectively. TCGA CESC methylation data showed that eight methylation sites of ATG5 could also be significantly associated with the overall survival (OS) of cervical cancer patients. Single-sample gene-set enrichment and gene functional enrichment results showed that ATG5 was correlated with some cancer-related pathways, such as phagocytosis-related genes, endocytosis-related genes, immune-related genes, EMT score, and some EMT signature-related genes. Next, cell migration and invasion assay and Western blot were applied to detect the function of ATG5 in EMT of cervical cancer. In cervical cancer cells, ATG5 knockdown resulted in attenuation of migration and invasion. The functional study showed that knockdown of ATG5 could reverse EMT process by P-ERK, P-NFκBp65, P-mTOR pathways, and so on. In conclusion, the present study implies that ATG5 was a major contributor to EMT regulation and poor prognosis in cervical cancer.
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Project description:Multiple myeloma is a hematological tumor with a malignant proliferation of myeloma cells. Although the survival time after treatment has improved, the recurrence rate of MM is still high. Choroideremia-like (CHML) protein is essential for the prenylation modification of various Rab proteins and it exerts biological effects on vesicle trafficking and signal transduction. However, little is identified about the relationship between CHML gene and MM. We integrated gene expression profiles of 1907 MM patients (1959 MM samples) from the 7 datasets. The relationship between CHML gene expression level and event-free survival (EFS), overall survival (OS), ISS stage, molecular subtype, relapse, therapy was analyzed. The differential gene exression profile of CHML-high MM group and CHML-low MM group and possible pathway related to CHML were conducted. Our data showed that EFS (P < 0.0001) and OS (P < 0.0001) in MM patients with high expression of CHML were lower than those with low CHML expression. The gene expression level of CHML was increased in subtypes of MM with poor prognosis, especially in proliferation subtype (P < 0.001). Cell division pathway (P < 0.01) was high enriched of the differential expressed genes of CHML-high group vs CHML-low group. CHML gene can be considered as an independent factor to evaluate the prognosis of MM. High expression of CHML is associated with poor survival, which is related to cell proliferation and cell division of myeloma cells.
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Project description:BackgroundAccumulating studies have focused on the oncogenic roles of the newly identified lncRNAs in human cancers. The aim of this study was to examine the expression pattern of Linc00959 in BC and to evaluate its biological role and clinical significance in prediction of prognosis.MethodsExpression of Linc00959 was detected in 290 BC tissues by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). We analyzed the relationship between Linc00959 expression and clinic pathological features of BC patients. The correlation was calculated by SPSS software.ResultsOur results revealed that Linc00959 expression was correlated with ER status (p = 0.005), PR status (p = 0.036), Ki67 (p = 0.025) and HER2 status (p = 0.009). The Kaplan-Meier survival curves indicated that the overall survival (OS) (p = 0.022) and relapse-free survival (RFS) (p = 0.002) were significantly poor in high Linc00959 expression BC patients (p = 0.023). Furthermore, the survival analysis by Cox regression showed that Linc00959 served as an independent prognostic marker in breast cancer (p = 0.004).ConclusionOur studies indicate that Linc00959 is significantly associated with poor prognosis and may represent a new marker of prognosis in breast cancer.
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