Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhou S
PROVIDER: S-EPMC8655861 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundPrevious studies have shown that RNA Polymerase III Subunit G (POLR3G) has oncogenic effects in cultured cells and mice. However, the role of POLR3G in transitional cell carcinoma (TCC) has not been reported. This study explores the potential of POLR3G as a novel molecular marker for TCC.MethodsThe RNA sequencing data and clinical information of patients with TCC were downloaded from The Cancer Genome Atlas official website. Transcriptome analysis was performed as implemented in the edgeR package to explore whether POLR3G was up-regulated in TCC tissues compared to normal bladder tissues. The expression of POLR3G in bladder cancer cell line T24 and human uroepithelial cell line SV-HUC-1 were detected via quantitative real time polymerase chain reaction (qRT-PCR). Correlations between POLR3G expression and clinicopathological characteristics were analyzed using Mann-Whitney U test or Kruskal-Wallis H test. Clinicopathological characteristics associated with overall survival were explored using the Kaplan-Meier method and Cox regression analyses. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different POLR3G expression phenotypes and the online tool Tumor IMmune Estimation Resource (TIMER) was used to explore the correlation between POLR3G expression and tumor immune infiltration in TCC.ResultsTranscriptome analysis showed that POLR3G was significantly up-regulated in TCC tissues compared to normal bladder tissues. Furthermore, qRT-PCR revealed high expression of POLR3G in T24 cells compared to SV-HUC-1 cells. Overall, POLR3G expression was associated with race, tumor status, tumor subtype, T classification, and pathological stage. Kaplan-Meier survival analysis revealed that higher POLR3G expression was associated with lower overall survival. The univariate Cox regression model revealed that age at diagnosis, pathological stage, and POLR3G expression were associated with prognosis of TCC patients. Further multivariate analyses identified these three clinicopathological characteristics as independent prognostic factors for overall survival. GSEA analysis showed that several gene sets associated with tumor development and metastasis, including TGF-β signaling, PI3K-AKT-mTOR signaling, and IL6-JAK-STAT3 signaling, were significantly enriched in POLR3G high expression phenotype. Immune infiltration analysis revealed that the expression of POLR3G was significantly correlated with infiltrating levels of immune cells, including CD8+ T cells, neutrophils, and dendritic cells; and the expression of POLR3G was also significantly correlated with the expression of immune checkpoint molecules, such as PD1, PD-L1, PD-L2, CTLA4, LAG3, HAVCR2, and TIGIT.ConclusionsPOLR3G was up-regulated in TCC and high POLR3G expression correlated with poor prognosis. POLR3G can potentially be used as a prognostic marker for TCC and might be of great value in predicting the response to immunotherapy.
| S-EPMC7646299 | biostudies-literature
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.
| S-EPMC9271802 | biostudies-literature
Project description:BackgroundRunt-related transcription factor 1 (RUNX1) was previously reported to play a dual role in promoting or suppressing tumorigenesis in various malignancies. A public dataset from The Cancer Genome Atlas (TCGA) was used to evaluate the role of RUNX1 in clear cell renal cell carcinoma (ccRCC).MethodsThe Wilcoxon signed-rank test was used to compare the expression of RUNX1 in ccRCC tissues and normal tissues. The Wilcoxon signed-rank test and logistic regression were utilized to investigate the relationship between clinicopathological factors and RUNX1 expression. Additionally, we analysed the differences in prognosis between patients with high and low expression of RUNX1 via the Kaplan-Meier method and Cox regression. Gene set enrichment analysis (GSEA) was performed to explore the mechanisms of RUNX1 in ccRCC.ResultsThe expression of RUNX1 in ccRCC tissues was significantly higher than that in normal tissues. High expression of RUNX1 was significantly associated with gender (p = 0.003), clinical stage (p < 0.001), tissue infiltration (p < 0.001), lymph node metastasis (p = 0.037) and histological grade (p < 0.001). Logistic regression analysis showed that high RUNX1 expression was significantly correlated with gender (OR = 1.71 for male vs. female, p = 0.004), histological grade (OR = 11.61 for grade IV vs. I, p < 0.001), clinical stage (OR = 1.55 for stage III/IV vs. I/II, p = 0.014) and tissue infiltration (OR = 1.54 for positive vs. negative, p = 0.018). Kaplan-Meier survival curves revealed that the prognosis of patients with ccRCC with high RUNX1 expression was worse than that of patients with ccRCC with low RUNX1 expression (p < 0.001). Univariate Cox regression analysis showed that high RUNX1 expression was strongly correlated with poor prognosis (HR = 1.60, 95% CI [1.31-1.97], p < 0.001). In addition, high expression of RUNX1 was an independent prognostic factor for poor overall survival (OS), with an HR of 1.50 (95% CI [1.20-1.87], p < 0.001) in multivariate Cox analysis. GSEA showed that the apoptosis, B cell receptor signalling pathway, calcium signalling pathway, chemokine signalling pathway, JAK/STAT signalling pathway, MAPK signalling pathway, p53 signalling pathway, pathways in cancer, T cell receptor signalling pathway, Toll-like receptor signalling pathway, VEGF signalling pathway, and Wnt signalling pathway were significantly enriched in the RUNX1 high-expression phenotype. In conclusion, RUNX1 can be used as a novel prognostic factor and therapeutic target in ccRCC.
| S-EPMC6778431 | biostudies-literature
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.
| S-EPMC9508458 | biostudies-literature
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.
| S-EPMC8038723 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a major life-threatening malignancy worldwide. HCC has an unfavorable prognosis, mainly due to late diagnosis, early metastasis, and post-surgical recurrence. Recent studies have demonstrated that beta-lactamases (LACTB) plays a pivotal role in the pathogenesis and progression of several malignant tumors, but its expression and functional role in HCC has not been reported. In this study, we explored the expression of LACTB using The Cancer Genome Atlas datasets and two independent tissues microarrays. We then analyzed the correlation between LACTB expression and clinical outcomes in HCC. We demonstrated that LACTB mRNA and protein levels were both down-regulated in HCC, and decreased LACTB expression was associated with TNM stage, histologic grade, and overall survival of patients. Additionally, through Gene Set Enrichment Analysis, we found that the genes negatively related to the survival of HCC patients were enriched in the low LACTB expression group. Furthermore, we confirmed that overexpression of LACTB inhibited HCC cell proliferation, invasion, and migration in vitro, as well as decreased tumor growth in vivo. Online prediction results suggested that the LACTB gene was markedly correlated with genes involved in the lipid metabolism pathway. In conclusion, these findings suggest that down-regulated LACTB could function as a novel biomarker for diagnosis and prognosis prediction, and LACTB could serve as a promising target in HCC therapy.
| S-EPMC6325492 | biostudies-literature
Project description:PurposeAs a member of the ubiquitin-conjugating enzyme (E2) family, UBE2V2 demonstrates significant tumorigenicity in many cancers. However, the relationship between UBE2V2 expression and the morbidity of lung adenocarcinoma (LUAD) is still unknown.MethodsWe detected the mRNA and protein expression of UBE2V2 and analyzed its relationship with clinical parameters as well as survival prognosis based on bioinformatic and immunohistochemistry (IHC) in LUAD. The signaling pathway of UBE2V2 in the development of LUAD was obtained by GSEA. The TIMER database was used to investigate the association between UBE2V2 expression and the level of infiltration of different immune cells. Finally, we explored the effects of UBE2V2 knockdown on the proliferation, apoptosis, and migration of LUAD cells.ResultsThe results showed that UBE2V2 was a potential oncogene and might be considered an independent prognostic molecule for LUAD patients based on TCGA prediction (HR: 1.497 p = 0.012) and IHC (HR:1.864 p = 0.044). IHC showed that UBE2V2 was related to the following clinicopathological factors: gender (p = 0.043), stage (p = 0.042), and lymph node metastasis (p = 0.002). Finally, knockdown of UBE2V2 reduced the migration of LUAD cells by regulating EMT-related proteins. Knockdown of UBE2V2 induced LUAD cells to arrest in the G1 phase. Knockdown of UBE2V2 increased LUAD cell apoptosis and decreased proliferation, which might be related to the downregulation of PCNA and upregulation of P53 and ƳH2AX expression. Interestingly, UBE2V2 is negatively correlated with B cells, CD4+ T cells, macrophages, and dendritic cells.ConclusionUBE2V2 may be a valuable therapeutic target for lung cancer.
| S-EPMC10587983 | biostudies-literature
Project description:Overexpression of synaptonemal complex protein-2 (SYCP2) has been identified in various human papillomavirus (HPV)-related carcinomas, whereas its significant role in breast carcinoma remains unclear. The aim of this study was to elucidate the prognostic value and potential function of SYCP2 in breast carcinoma. Herein, data for breast carcinoma patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas database (TCGA) were analyzed. The enrichment analysis of SYCP2 including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Friends, and GSEA was performed. Kaplan-Meier analysis, Cox regression, and receiver operating characteristic (ROC) curves were employed for determining the predictive value of SYCP2 on clinical outcomes in patients suffering from breast carcinoma. A nomogram was generated to predict the effect arising from SYCP2 on prognosis. The association analysis of SYCP2 gene expression and diverse immune infiltration levels was conducted through ssGSEA and ESTIMATE analysis, which consisted of dendritic cell (DC), neutrophil, eosinophil, macrophage, mast cell, NK cell, and other 18 cell subtypes. The results showed that SYCP2 expression was significantly elevated in breast carcinoma tissues as compared with that of normal tissues (p < 0.001). SYCP2 plays a certain role in pathways related to DNA methylation, keratinocyte differentiation, steroid hormone biosynthesis, and immune infiltration. The high expression of SYCP2 had a significant relationship to age, pathological type, ER expression, and PR expression (p < 0.001). Kaplan-Meier survival analysis showed that patients suffering from breast carcinoma characterized by high-SYCP2 expression had a poorer prognosis than patients with low-SYCP2 expression (p = 0.005). Univariate and multivariate Cox regression analyses revealed that SYCP2 had an independent relationship to overall survival (p = 0.049). Moreover, ROC curves suggested the significant diagnostic ability of SYCP2 for breast carcinoma, and as time went on, SYCP2 had more accurate prognostic efficacy. Furthermore, a high level of SYCP2 expression was found to have a relationship to poor prognosis of breast carcinoma in the subgroups of T3, N0, and M0, and infiltrating ductal carcinoma (HR > 1, p < 0.05). The calibration plot of the nomogram indicated that the SYCP2 model has an effective predictive performance for breast carcinoma patients. Conclusively, SYCP2 plays a vital role in the pathogenesis and progression of human breast carcinoma, so it may serve as a promising prognostic molecular marker of poor survival.
| S-EPMC9491682 | biostudies-literature
Project description:The 5-methylcytosine (m5C) RNA methyltransferase NOP2/Sun RNA methyltransferase 5 (NSUN5) has been reported to serve important roles in numerous diseases. However, the functions and clinical significance of NSUN5 in hepatocellular carcinoma (HCC) remain unknown. Clinical information and NSUN5 mRNA sequencing data for 374 patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and NSUN5 mRNA and protein expression levels in 120 patients with HCC (present study cohorts) were assessed using reverse transcription-quantitative PCR, western blotting or immunohistochemistry. The association between NSUN5 mRNA and protein expression levels and the clinical characteristics (or prognosis) of patients with HCC was analyzed using the χ2 or log-rank test. The functions of NSUN5 in HCC were evaluated using in vitro and in vivo experiments, and the mechanism by which NSUN5 affected the progression of HCC was assessed using bioinformatics analysis using LinkedOmics. NSUN5 was significantly upregulated and predicted poor prognosis in HCC according to data from both TCGA database and present study cohorts. NSUN5 significantly promoted HCC proliferation and migration in vitro and significantly induced HCC tumor growth in vivo. Bioinformatics analysis demonstrated that NSUN5 was positively correlated with genes associated with translation in HCC. It was hypothesized that overexpression of NSUN5 strengthened ribosome functions and global protein translation, which may promote the proliferation and migration of HCC. In conclusion, NSUN5 may promote the progression of HCC by enhancing translation, thus making it a potential target for HCC treatment.
| S-EPMC9641807 | biostudies-literature
Project description:Metastasis is a serious risk that may occur during the treatment of hepatocellular carcinoma (HCC), preventing many patients from being surgical candidates and contributing to poor prognosis. Hypoxia has been proved an important factor of metastasis through the epithelial-mesenchymal transition (EMT) pathway. Acetyl-CoA synthase 2 (ACSS2) provides an acetyl group for the acetylation of hypoxia-inducible factor (HIF)-2?, and this epigenetic modification affects the activity of HIF-2? and the subsequent EMT process. Here, we showed that ACSS2 expression was negatively correlated with HCC malignancy. Knockdown of ACSS2 increased the invasion and migration ability of HCC cells and promoted EMT without increasing the total protein level of HIF-2?, even in hypoxic conditions. The immunoprecipitation assay revealed downregulated acetylation levels of HIF-2? after ACSS2 knockdown in hypoxic conditions, which resulted in enhanced HIF-2? activity. Finally, decreased expression of ACSS2 was found to be related to advanced stage and poor overall survival and disease-free survival rates in a cohort of patients with HCC. In conclusion, ACSS2 plays an important role in the acetylation process of HIF-2?, which effectively modifies the activity of HIF-2? under hypoxic conditions and greatly impacts on the prognosis of patients with HCC.
| S-EPMC5497799 | biostudies-other