Low Expression of RILPL2 Predicts Poor Prognosis and Correlates With Immune Infiltration in Endometrial Carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu J
PROVIDER: S-EPMC8171931 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:CXC ligand 17 (CXCL17) is a novel CXC chemokine whose clinical significance remains largely unknown. In the present study, we characterized the prognostic value of CXCL17 in patients with hepatocellular carcinoma (HCC) and evaluated the association of CXCL17 with immune infiltration. We examined CXCL17 expression in 227 HCC tissue specimens by immunohistochemical staining, and correlated CXCL17 expression patterns with clinicopathological features, prognosis, and immune infiltrate density (CD4 T cells, CD8 T cells, B cells, natural killer cells, neutrophils, macrophages). Kaplan-Meier survival analysis showed that both increased intratumoral CXCL17 (P = 0.015 for overall survival [OS], P = 0.003 for recurrence-free survival [RFS]) and peritumoral CXCL17 (P = 0.002 for OS, P<0.001 for RFS) were associated with shorter OS and RFS. Patients in the CXCL17low group had significantly lower 5-year recurrence rate compared with patients in the CXCL17high group (peritumoral: 53.1% vs. 77.7%, P<0.001, intratumoral: 58.6% vs. 73.0%, P = 0.001, respectively). Multivariate Cox proportional hazards analysis identified peritumoral CXCL17 as an independent prognostic factor for both OS (hazard ratio [HR] = 2.066, 95% confidence interval [CI] = 1.296-3.292, P = 0.002) and RFS (HR = 1.844, 95% CI = 1.218-2.793, P = 0.004). Moreover, CXCL17 expression was associated with more CD68 and less CD4 cell infiltration (both P<0.05). The combination of CXCL17 density and immune infiltration could be used to further classify patients into subsets with different prognosis for RFS. Our results provide the first evidence that tumor-infiltrating CXCL17+ cell density is an independent prognostic factor that predicts both OS and RFS in HCC. CXCL17 production correlated with adverse immune infiltration and might be an important target for anti-HCC therapies.
| S-EPMC4193880 | biostudies-literature
Project description:BackgroundRecent evidence has shown that Solute Carrier Family 39 Member 10 (SLC39A10) promoted tumor progression in several cancer types. The study intended to explore the expression and function of SLC39A10 in hepatocellular carcinoma (HCC).MethodsMultiple bioinformatics analyses were used to evaluate SLC39A10 expression and potential role in HCC. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to confirm SLC39A10 expression. Intro studies were performed to assess the effects of SLC39A10 on HCC cells proliferation and migration. Furthermore, flow cytometry was conducted to identify its specific function in apoptosis of HCC.ResultsSLC39A10 was significantly over-expressed in HCC samples from both bioinformatic databases and our cohort. Survival analyses suggested patients with high expression of SLC39A10 had poor overall survival and disease-free survival (P-value <0.01). Further, the expression of SLC39A10 was positively correlated with tumor-infiltrating lymphocytes and some immune checkpoints like CTLA4, TIM3 and TGFB1. In HCC cell lines, SLC39A10 knockdown inhibited cells proliferation and migration, but promoted apoptosis.ConclusionAn increased SLC39A10 expression was found and served as an unfavorable indicator of survival in HCC. Further studies suggested SLC39A10 promotes tumor aggressiveness and may provide a novel target for HCC therapy.
| S-EPMC8357404 | biostudies-literature
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.
| S-EPMC9896754 | biostudies-literature
Project description:BackgroundGlucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a key enzyme in the hexosamine biosynthetic pathway (HBP), which functions as promoting proliferation in some tumors, yet its potential biological function and mechanism in lung adenocarcinoma (LUAD) have not been explored.MethodsThe mRNA differential expression of GNPNAT1 in LUAD and normal tissues was analyzed using the Cancer Genome Atlas (TCGA) database and validated by real-time PCR. The clinical value of GNPNAT1 in LUAD was investigated based on the data from the TCGA database. Then, immunohistochemistry (IHC) of GNPNAT1 was applied to verify the expression and clinical significance in LUAD from the protein level. The relationship between GNPNAT1 and epigenetics was explored using the cBioPortal database, and the miRNAs regulating GNPNAT1 were found using the miRNA database. The association between GNPNAT1 expression and tumor-infiltrating immune cells in LUAD was observed through the Tumor IMmune Estimation Resource (TIMER). Finally, Gene set enrichment analysis (GSEA) was used to explore the biological signaling pathways involved in GNPNAT1 in LUAD.ResultsGNPNAT1 was upregulated in LUAD compared with normal tissues, which was verified through qRT-PCR in different cell lines (P < 0.05), and associated with patients' clinical stage, tumor size, and lymphatic metastasis status (all P < 0.01). Kaplan-Meier (KM) analysis suggested that patients with upregulated GNPNAT1 had a relatively poor prognosis (P < 0.0001). Furthermore, multivariate Cox regression analysis indicated that GNPNAT1 was an independent prognostic factor for LUAD (OS, TCGA dataset: HR = 1.028, 95% CI: 1.013-1.044, P < 0.001; OS, validation set: HR = 1.313, 95% CI: 1.130-1.526, P < 0.001). GNPNAT1 overexpression was correlated with DNA copy amplification (P < 0.0001), low DNA methylation (R = -0.52, P < 0.0001), and downregulation of hsa-miR-30d-3p (R = -0.17, P < 0.001). GNPNAT1 expression was linked to B cells (R = -0.304, P < 0.0001), CD4+T cells (R = -0.218, P < 0.0001), and dendritic cells (R = -0.137, P = 0.002). Eventually, GSEA showed that the signaling pathways of the cell cycle, ubiquitin-mediated proteolysis, mismatch repair and p53 were enriched in the GNPNAT1 overexpression group.ConclusionGNPNAT1 may be a potential prognostic biomarker and novel target for intervention in LUAD.
| S-EPMC8027087 | biostudies-literature
Project description:BackgroundMany researches proved that non-coding RNAs are important in glioma development. We screened the differentially expressed genes through The Cancer Genome Atlas (TCGA) database and identified the molecule LYRM4-AS1 associated with prognosis. As a lncRNA, the expression level and role of LYRM4-AS1 in glioma are inconclusive. Therefore, we attempted to assess the clinical significance, expression and related mechanisms of LYRM4-AS1 in glioma by employing cell experiments and an integrative in silico methodology.MethodsRNA-seq data were obtained from UCSC XENA and TCGA datasets. The Gene Expression Omnibus (GEO) database was used to download glioma-related expression profile data. The LYRM4-AS1 expression level was evaluated. Survival curves were constructed by the Kaplan-Meier method. Cox regression analysis was used to analyze independent variables. Patients were divided into high and low expression group base on the median LYRM4-AS1 expression value in glioma tissues. The DESeq2 R package was used to identify differentially expressed genes (DEGs) between two different expression LYRM4-AS1 groups. Gene set enrichment analysis (GSEA) was conducted. Next, the single-sample Gene Set Enrichment Analysis (ssGSEA) was done to quantify the immune infiltration of immune cells in glioma tissues. Gene expression profiles for glioma tumor tissues were used to quantify the relative enrichment score for each immune cell. Spearman correlation analysis was used to analyze the correlation between LYRM4-AS1 and biomarkers of immune cells as well as immune checkpoints in glioma. Finally, assays for cell apoptosis, cell viability and wound healing were conducted to evaluate the function on U87 MG and U251 cells after knocking down LYRM4-AS1.ResultsWe found that LYRM4-AS1 was upregulated and related to the grade and malignancy of glioma. Survival analyses showed that high expression LYRM4-AS1 patients had poor clinical outcomes (P < 0.01). Cox regression analyses demonstrated that LYRM4-AS1 was an independent risk factor for overall survival (OS) in glioma (HR: 274 1.836; CI [1.278-2.639]; P = 0.001). Enrichment and immune infiltration analysis showed interferon signaling and cytokine-cytokine receptor interaction enriched in the LYRM4-AS1 high-expression phenotype, and LYRM4-AS1 showed significantly positively related to immune infiltration as well as immune checkpoints (P < 0.01). The knockdown of LYRM4-AS1 in U87 MG and U251 cells can inhibit migration and proliferation of cells (P < 0.05).ConclusionsThese findings indicated that the increased LYRM4-AS1 may be useful for the diagnosis and prognosis of glioma and might participate in the immune infiltration.
| S-EPMC10557942 | biostudies-literature
Project description:Background: Endometrial cancer (EC) is one of the most common gynecological malignancies in women. Cholesterol metabolism has been confirmed to be closely related to tumor proliferation, invasion and metastasis. However, the correlation between cholesterol homeostasis-related genes and prognosis of EC remains unclear. Methods: EC patients from the Cancer Genome Atlas (TCGA) database were randomly divided into training cohort and test cohort. Transcriptome analysis, univariate survival analysis and LASSO Cox regression analysis were adopted to construct a cholesterol homeostasis-related gene signature from the training cohort. Subsequently, Kaplan-Meier (KM) plot, receiver operating characteristic (ROC) curve and principal component analysis (PCA) were utilized to verify the predictive performance of the gene signature in two cohorts. Additionally, enrichment analysis and immune infiltration analysis were performed on differentially expressed genes (DEGs) between two risk groups. Results: Seven cholesterol homeostasis-related genes were selected to establish a gene signature. KM plot, ROC curve and PCA in two cohorts demonstrated that the gene signature was an efficient independent prognostic indicator. The enrichment analysis and immune infiltration analysis indicated that the high-risk group generally had lower immune infiltrating cells and immune function. Conclusion: We constructed and validated a cholesterol homeostasis-related gene signature to predict the prognosis of EC, which correlated to immune infiltration and expected to help the diagnosis and precision treatment of EC.
| S-EPMC8591263 | biostudies-literature
Project description:BackgroundExpression levels of transmembrane protein 41A (TMEM41A) are related to the progression of malignant tumors. However, the association between TMEM41A expression and endometrial carcinoma (EC) remains unclear. This study aims to identify the roles of TMEM41A expression in the prognosis of patients with EC and its correlation with EC progression.MethodsThe TMEM41A expression and its correlation with the survival of patients with EC were assessed. Cox regression analysis was used to identify the prognostic factors, while nomograms were used to examine the association between the prognostic factors and the survival of patients with EC. Finally, the link between TMEM41A level and immune microenvironment and RNA modifications was investigated in EC.ResultsTMEM41A was overexpressed in EC. TMEM41A overexpression could diagnose the EC and evaluate the poor prognosis of patients. Overexpression of TMEM41A was associated with clinical stage, age, weight, histological subtype, tumor grade, and survival status of patients with EC. Clinical stage, age, tumor grade, radiotherapy, and TMEM41A overexpression were factors of poor prognosis in patients with EC. The nomograms revealed the correlation between the TMEM41A level and survival time of patients with EC at 1, 3, and 5 years. Furthermore, TMEM41A overexpression was significantly correlated with the level of the stromal score, immune score, estimate score, NK CD56 bright cells, iDC, NK cells, eosinophils, pDC, T cells, TReg, cytotoxic cells, mast cells, Th17 cells, neutrophils, aDC, NK CD56 dim cells, TFH, Th2 cells, CD8 T cells, macrophages, immune cell markers, and RNA modifications.ConclusionsTMEM41A is overexpressed in EC tissues and is associated with the prognosis, immune microenvironment, and RNA modification. Our preliminary studies indicate that overexpression of TMEM41A can potentially serve as a biomarker for EC treatment.
| S-EPMC10361503 | biostudies-literature
Project description:BackgroundSpindle and kinetochore-associated complex subunit 3 (SKA3) is a malignancy-associated gene that plays a critical role in the regulation of chromosome separation and cell division. However, the molecular mechanism through which SKA3 regulates tumor cell proliferation in hepatocellular carcinoma (HCC) has not been fully elucidated.AimTo investigate the molecular mechanisms underlying the role of SKA3 in HCC.MethodsSKA3 expression, clinicopathological, and survival analyses were performed using multiple public database platforms, and the results were verified by Western blot and immunohistochemistry staining using collected clinical samples. Functional enrichment analyses were performed to evaluate the biological functions and molecular mechanisms of SKA3 in HCC. Furthermore, the Tumor Immune Estimation Resource and single-sample Gene Set Enrichment Analysis (ssGSEA) algorithms were utilized to investigate the abundance of tumor-infiltrating immune cells in HCC. The response to chemotherapeutic drugs was evaluated by the R package "pRRophetic".ResultsWe found that upregulated SKA3 expression was significantly correlated with poor prognosis in patients with HCC. Multivariable Cox regression analysis indicated that SKA3 was an independent risk factor for survival. GSEA revealed that SKA3 expression may facilitate proliferation and migratory processes by regulating the cell cycle and DNA repair. Moreover, patients with high SKA3 expression had significantly decreased ratios of CD8+ T cells, natural killer cells, and dendritic cells. Drug sensitivity analysis showed that the high SKA3 group was more sensitive to sorafenib, sunitinib, paclitaxel, doxorubicin, gemcitabine, and vx-680.ConclusionHigh SKA3 expression led to poor prognosis in patients with HCC by enhancing HCC proliferation and repressing immune cell infiltration surrounding HCC. SKA3 may be used as a biomarker for poor prognosis and as a therapeutic target in HCC.
| S-EPMC10494596 | biostudies-literature
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.
| S-EPMC9256401 | biostudies-literature
Project description:IntroductionHepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Identifying specific molecular markers that can predict HCC prognosis is extremely important. The protein deoxythymidylate kinase (DTYMK) has been reported to contribute to unfavorable prognosis in non-small cell lung cancer patients, but its role in the prediction of HCC patient prognosis has not been clarified.MethodsSamples from the TCGA and GEO databases were consecutively enrolled for gene expression analysis, clinicopathology analysis, immune microenvironment analysis and chemotherapeutic response prediction. The results were validated using 86 samples from the First Affiliated Hospital of Sun Yat-sen University. Cox regression analysis was used to analyze the effect of DTYMK on progression-free survival (PFS) and overall survival (OS). Functional enrichment analysis was used to describe the marker pathways that were significantly related to DTYMK. TIMER (Tumor Immune Estimation Resource), TISIDB (Tumor and Immune System Interaction DataBase) and CIBERSORT (Cell type Identification By Estimating Relative Subsets Of RNA Transcripts) were used to explore the immune microenvironment.ResultsWe found that DTYMK expression upregulation is associated with poor prognosis in HCC patients and tightly related to the pathways regulating the cell cycle and acid metabolism. Our findings revealed that hepatocellular carcinoma cell lines with high DTYMK expression were more sensitive to sorafenib and many other chemotherapeutic drugs. We also found an inhibiting effect of DTYMK on the immune microenvironment in the process of tumorigenesis.DiscussionWe found that DTYMK has potential as a new prognostic and chemotherapeutic response biomarker for HCC patients and correlates with the immune microenvironment in HCC. However, there are some deficiencies in our study. First, this is a retrospective study that may lead to selection bias. Second, the protein expression of DTYMK was investigated via immunohistochemical analysis. Finally, we did not explore the exact underlying molecular mechanisms of DTYMK in tumorigenesis in this study, which is needed to be clarified in future research.
| S-EPMC8349219 | biostudies-literature