Dataset Information

High expression of EMP1 predicts a poor prognosis and correlates with immune infiltrates in bladder urothelial carcinoma.

ABSTRACT: Epithelial membrane protein 1 (EMP1) is a key gene that regulates cell proliferation and metastatic capability in various types of cancer, and serves an important role in tumor-immune interactions. However, the association between EMP1 and clinical prognosis, as well as the presence of tumor-infiltrating lymphocytes in bladder urothelial carcinoma (BLCA) remains unclear. The present study aimed to explore the relationship between EMP1 expression and tumor immune cell infiltration in BLCA. In the present study, EMP1 expression in BLCA was analyzed using the Oncomine database, The Cancer Genome Atlas (TCGA) and the Tumor Immune Estimation Resource (TIMER). The effects of EMP1 on clinical prognosis were evaluated using the Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis. The correlations between EMP1, cancer immune infiltrates and lymphocyte abundance were determined using the TIMER and Tumor immune system interaction database. In addition, correlations between EMP1 expression and gene markers in immune infiltrates were analyzed using cBioportal. The results demonstrated that, compared with adjacent normal tissues, EMP1 was downregulated in BLCA tissues. High expression of EMP1 was significantly associated with poor overall survival (OS) in BLCA cases obtained from TCGA. Multivariate Cox analysis revealed that EMP1 was an independent predictor of OS in patients with BLCA. Gene set enrichment analysis revealed that EMP1 was associated with cancer-related pathways and was positively correlated with the levels of infiltrating CD8+ T cells, macrophages, neutrophils and dendritic cells in BLCA. Further analysis demonstrated that EMP1 was significantly associated with the enrichment of multiple types of lymphocyte. EMP1 expression exhibited a strong correlation with a range of immune markers in BLCA. In conclusion, the results of the present study demonstrated that EMP1 was associated with a poor prognosis in patients with BLCA, and that the levels of immune infiltration and multiple immunomarker groups were associated with EMP1 expression. These results suggested that EMP1 may be used as a predictive biomarker to determine the prognosis and immune infiltration in BLCA.

SUBMITTER: Lin B

PROVIDER: S-EPMC7400100 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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High expression of EMP1 predicts a poor prognosis and correlates with immune infiltrates in bladder urothelial carcinoma.

Lin Bo B Zhang Tianwen T Ye Xin X Yang Hongyu H

Oncology letters 20200709 3

Epithelial membrane protein 1 (EMP1) is a key gene that regulates cell proliferation and metastatic capability in various types of cancer, and serves an important role in tumor-immune interactions. However, the association between EMP1 and clinical prognosis, as well as the presence of tumor-infiltrating lymphocytes in bladder urothelial carcinoma (BLCA) remains unclear. The present study aimed to explore the relationship between EMP1 expression and tumor immune cell infiltr ...[more]

PMID: 32782602

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Project description:Pentatricopeptide repeat domain 1 (PTCD1) was reported to regulate mitochondrial metabolism and oxidative phosphorylation. However, the effect and mechanism of PTCD1 in the development of bladder urothelial carcinoma (BLCA) remain unclear. The databases from The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) were used to analyze the expression changes, clinical features, and prognostic values of PTCD1. A nomogram was built to predict the prognostic outcomes of BLCA cases. The potential genes interacting with PTCD1 were explored by Weighted Gene Coexpression Network Analysis (WGCNA). The estimation of associations between PTCD1 and tumor mutations, tumor immunities, and m6A methylations was performed. The study found that the gradual decrease of PTCD1 expression was observed with the increase of stage and grade. Low PTCD1 expression was greatly correlated with higher pathological stage, N stage, and poor prognosis in TCGA cohorts; interestingly, low-grade BLCA cases all exhibited high expression of PTCD1. HPA database analysis implied that the expression of PTCD1 protein in BLCA was lower than that in normal bladder tissue, and the protein expression of PTCD1 in high-grade BLCA was lower than that in low-grade BLCA. Multivariate Cox regression analysis indicated that PTCD1 may serve as an independent factor influencing prognosis of BLCA. Mechanistically, PTCD1 played a regulatory role in BLCA progression through multiple tumor-related pathways containing PI3K-Akt signaling, ECM-receptor interaction, oxidative phosphorylation, and extracellular matrix organization. WGCNA reported that PTCD1 had a strong positive correlation with POLR2J, ZNHT1, ATP5MF, PDAP1, BUD31, and COPS6. Besides, the mRNA expression of PTCD1 was negatively associated with immune cells' infiltrations, immune functions, and checkpoints, especially with some m6A methylation regulators in BLCA. In sum, downregulation of PTCD1 expression may be involved in the development of BLCA and remarkably correlated with poor prognosis. Meantime, it showed an influence in immune cell infiltration and may serve as an agreeable prognostic indicator in BLCA.

Project description:BackgroundIGF2BP3 expression is associated with poor prognosis in cancers of multiple tissue origins. However, the precise mechanism of its co-carcinogenic action in bladder cancer is unknown.MethodsWe aimed to demonstrate the relationship between IGF2BP3 expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. We next validated IGF2BP3 expression in the Gene Expression Omnibus (GEO) database (GSE3167). Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic values of IGF2BP3. Cox and logistic regression were used to explore the factors affecting the prognosis. Protein-protein interactions (PPIs) network was constructed by STRING. Enrichment analyses were performed to infer involved pathways and functional categories of IGF2BP3 using the cluster Profiler package. We applied single-sample gene set enrichment analysis (ssGSEA) algorithm and TIMER database to evaluate the expression level of immune genes.ResultsPan-cancer analyses reveal that IGF2BP3 was higher in most cancer types, including bladder cancer, and the same results were found in GSE3167. The area under the ROC curve of IGF2BP3 was 0.736, which indicated that IGF2BP3 may be a potential diagnostic biomarker. High IGF2BP3 expression was associated with poorer overall survival (OS) (P = 0.015). For validation, we collected 95 bladder cancer samples and found that IGF2BP3 expression was higher in bladder cancer tissues than that in non-tumor bladder tissues by immunohistochemistry staining. We found a positive correlation between the expression level of IGF2BP3 and the clinical stage of bladder cancer. Immunocyte infiltration analysis showed that high IGF2BP3 expression was correlated with regulating the infiltration level of immune cell, including neutrophil cells and macrophages. IGF2BP3 promotes migration and invasion of bladder cancer cells, while IGF2BP3 inhibition had the opposite effects. Higher IGF2BP3 expression was closely associated with advanced TNM stage.ConclusionIGF2BP3 overexpression was related to disease progression and poor prognosis, as well as infiltration of immune cells in bladder cancer. IGF2BP3 can be a promising independent prognostic biomarker and potential treatment target for bladder cancer.

Project description:Background: Petite Integration Factor 1 (PIF1) is a multifunctional helicase and DNA processing enzyme that plays an important role in the process of several cancer types. However, the relationship between clear cell renal cell carcinoma (ccRCC) and PIF1 remains unclear. This study aims to explore the role of PIF1 in ccRCC tumorigenesis and prognosis. Methods: Based on The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, we retrieved and verified the expression of PIF1 in ccRCC tissues as well as normal tissues. To assess the protein expression of PIF1 by using the Human Protein Atlas and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). We also performed receiver operating characteristic (ROC) curve analysis to differentiate the effectiveness of PIF1 in ccRCC and adjacent normal tissues. To evaluate the value of PIF1 on clinical outcomes in ccRCC patients by using multivariate methods and Kaplan‒Meier survival curves. Protein‒protein interaction (PPI) networks were made with STRING. We determined the relationship between the expression of PIF1 and immune cell infiltration with single-sample gene set enrichment analysis (ssGSEA). Results: Compared with normal tissues, the expression of PIF1 was significantly elevated in ccRCC. The mRNA expression of PIF1 is correlated with high TNM stage and high pathologic stage. The receiver operating characteristic (ROC) curve analysis showed that PIF1 was related to an area under the curve (AUC) value of 0.928 to distinguish between ccRCC tissues and normal tissues. Kaplan‒Meier survival analysis showed that the overall survival (OS) of ccRCC patients with a high level of PIF1 was significantly shorter than that of those with a low level of PIF1. PIF1 may play an important role in the occurrence of tumors. Correlation analysis showed that PIF1-mediated carcinogenesis may participate in the process of tumor immune escape in ccRCC. Conclusion: PIF1 could be a reference biomarker to identify ccRCC patients with poor prognosis. PIF1 may play a distinct role in the microenvironment of ccRCC by regulating tumor infiltration of immune cells, which is a new therapeutic target to affect the growth of the tumor.

Project description:BackgroundThe bifunctional methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase (MTHFD2) has been reported to play an oncogenic role in various types of cancers. However, the function of MTHFD2 in urothelial carcinomas of bladder (UCB) and its association with tumor immune infiltration remains unknown. We aim to examine the suitability of MTHFD2 to be a novel biomarker of bladder cancer and whether MTHFD2 is linked to immune infiltration.MethodsRNA sequencing data and clinical information (bladder cancer samples: normal samples = 414: 19) were downloaded from The Cancer Genome Atlas official website. Western blot analysis was performed to detect MTHFD2 expression in human bladder cancer (BLCA) cells and normal urothelial cell line SV-HUC-1. Associations between MTHFD2 expression and clinicopathological features were analyzed using Mann Whitney U test or Kruskal-Wallis H test. The "survival" and "survminer" packages were utilized to plot Kaplan-Meier survival curves. Moreover, the gene set enrichment analysis (GSEA) was conducted using a clusterProfiler package. The correlation of MTHFD2 expression with immune infiltration level was estimated using the single sample GSEA (ssGSEA) algorithm. Furthermore, associations between MTHFD2 and immune checkpoint genes were evaluated using the correlation analysis.ResultsTranscriptome analysis manifested that MTHFD2 was highly expressed in UCB tissues than normal bladder tissues, which was further confirmed by western blot analysis in human BLCA cells and SV-HUC-1 cells. Moreover, MTHFD2 high expression was significantly associated with the advanced disease progression. Also, the high expression of MTHFD2 was correlated with poor prognosis, and MTHFD2 was considered as an independent prognostic factor for disease specific survival. Furthermore, a number of cancer-related pathways were enriched in MTHFD2 high group, including NF-κB activation, JAK/STAT, and cancer immunotherapy by PD1 blockade. Several immune checkpoint molecules were also strongly associated with MTHFD2 expression, including PDCD1, CD274, CTLA4, CD276, LAG3, HAVCR2, and TIGIT.ConclusionsMTHFD2 expression was remarkably elevated in UCB, suggesting that MTHFD2 could be a promising biomarker for BLCA as well as novel target for anti-cancer immunotherapy since its close association with immune infiltration.

Dataset Information

High expression of EMP1 predicts a poor prognosis and correlates with immune infiltrates in bladder urothelial carcinoma.

Publications

High expression of <i>EMP1</i> predicts a poor prognosis and correlates with immune infiltrates in bladder urothelial carcinoma.

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