KIF18B is a Prognostic Biomarker and Correlates with Immune Infiltrates in Pan-Cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Qiu MJ
PROVIDER: S-EPMC8182049 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Objective: Prolyl 4-hydroxylase, alpha polypeptide I (P4HA1), a key enzyme in collagen synthesis, comprises two identical alpha subunits and two beta subunits. However, the immunomodulatory role of P4HA1 in tumor immune microenvironment (TIME) remains unclear. This study aimed to evaluate the prognostic value of P4HA1 in pan-cancer and explore the relationship between P4HA1 expression and TIME. Methods: P4HA1 expression, clinical features, mutations, DNA methylation, copy number alteration, and prognostic value in pan-cancer were investigated using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data. Pathway enrichment analysis of P4HA1 was performed using R package "clusterProfiler." The correlation between immune cell infiltration level and P4HA1 expression was analyzed using three sources of immune cell infiltration data, including ImmuCellAI database, TIMER2 database, and a published work. Results: P4HA1 was substantially overexpressed in most cancer types. P4HA1 overexpression was associated with poor survival in patients. Additionally, we discovered that P4HA1 expression was positively associated with infiltration levels of immunosuppressive cells, such as tumor-associated macrophages, cancer-associated fibroblasts, nTregs, and iTregs, and negatively correlated with CD8+ T and NK cells in pan-cancer. Conclusions: Our results highlighted that P4HA1 might serve as a potential prognostic biomarker in pan-cancer. P4HA1 overexpression is indicative of an immunosuppressive microenvironment. P4HA1 may be a potential target of immunotherapy.
| S-EPMC8710955 | biostudies-literature
Project description:Epidermal growth factor receptor 2 (ERBB2) is commonly over-expressed in advanced or metastatic tissues of papillary thyroid cancer (PTC) with poor prognosis, while it remains unknown whether ERBB2 plays a role in the progression of PTC. Thus, we analyzed the data derived from online repositories, including TCGA, KEGG, GO, GeneMANIA, and STRING, to explore the relationship between ERBB2 expression and prognosis, tumor phenotypes of interest, and immune infiltrates in PTC. Compared to normal thyroid tissue, ERBB2 was up-regulated in PTC samples (p < 0.001); In comparison with the group with low expression of ERBB2, the group with high expression of ERBB2 had poorer progression-free interval in stage III/IV patients (p = 0.008) and patients aged >45 years (p = 0.019). The up-regulated ERBB2 was associated with iodine metabolism dysfunction, proliferation, metastasis, angiogenesis, and drug resistance. The expression of ERBB2 negatively correlated with enrichment scores of B cells (r = -0.176, p < 0.001), CD8+ T cells (r = -0.160, p < 0.001), cytotoxic cells (r = -0.219, p < 0.001), NK CD56dim cells (r = -0.218, p < 0.001), plasmacytoid dendritic cells (r = -0.267, p < 0.001), T cells (r = -0.164, p < 0.001), T follicular helper cells (r = -0.111, p = 0.012), gamma delta T cells (r = -0.105, p = 0.017), and regulatory T cells (r = -0.125, p = 0.005). In conclusion, ERBB2 may serve as a prognostic biomarker and an immunotherapeutic target in PTC, deserving further exploration.
| S-EPMC9682178 | biostudies-literature
Project description:BackgroundMore and more evidence suggests that cancer is a mitochondrial metabolic disease recently and mitochondria dysfunction is critical to tumorigenesis. As a gatekeeper of mitochondria, the voltage-dependent anion channel 1 (VDAC1) is associated with the development of breast cancer (BC). However, its potential mechanism and clinical significance remain unclear; thus, in this research, we aimed to explore it.MethodsVDAC1 expression in BC tissues and normal tissues was obtained from The Cancer Genome Atlas (TCGA) and validated by datasets from the gene expression omnibus (GEO) database. Then, the relationships between VDAC1 expression and clinicopathological features were analyzed. Receiver operating characteristics (ROC) curves were used to identify the diagnostic value of VDAC1. The prognostic value was evaluated by Kaplan-Meier survival curves and Cox regression analysis. VDAC1 with its co-expression genes were subjected to enrichment analysis to explore potential mechanisms in BC and the protein-protein interaction (PPI) network was constructed. At last, the association between VDAC1 expression and infiltration levels of immune cell infiltration by various methods, as well as their corresponding markers, was analyzed. We also analyzed the correction between VDAC1 expression and eight immune checkpoint genes and the tumor immune dysfunction and exclusion (TIDE) scores of each BC sample in TCGA were calculated and the differences between high and low VDAC1 expression groups were analyzed.ResultsVDAC1 expression was remarkably elevated in BC (p < 0.001), and high expression of VDAC1 was associated with the positive expression of ER (p = 0.004), PR (p = 0.033), and HER2 (p = 0.001). ROC analysis suggested that VDAC1 had diagnosed value in BC. The Kaplan-Meier analysis suggested that higher expression of VDAC1 was associated with shorter overall survival (OS), and further Cox regression analysis revealed that VDAC1 was an independent factor of unfavorable prognosis in BC patients. Enrichment analysis of VDAC1 and its co-expression suggested that VDAC1 was related to the regulation of mitochondrial energy metabolism and protein modification, and the HIF-1 singing pathway might be the potential mechanism in BC. Notably, we found that VDAC1 expression was infiltration levels of most types of immune cells, as well as the expression of marker genes of immune cells. The ICGs PDCD1, CTLA4, LAG3, SIGLEC15, and TIGIT were negatively corrected with VDAC1 expression in BC. TIDE scores between the low and high expression groups showed no difference.ConclusionOverexpressed VDAC1 in BC could be severed as a novel biomarker for diagnosis and VDAC1 was an independent factor for adverse prognosis prediction. Our study revealed that VDAC1 might inhibit tumor immunity and might be a novel therapeutic target in BC.
| S-EPMC9215028 | biostudies-literature
Project description:CXCs are important genes that regulate inflammation and tumor metastasis. However, the expression level, prognosis value, and immune infiltration of CXCs in cancers are not clear. Multiple online datasets were used to analyze the expression, prognosis, and immune regulation of CXCs in this study. Network analysis of the Amadis database and GEO dataset was used to analyze the regulation of intestinal flora on the expression of CXCs. A mouse model was used to verify the fact that intestinal bacterial dysregulation can affect the expression of CXCs. In the three cancers, multiple datasets verified the fact that the mRNA expression of this family was significantly different; the mRNA levels of CXCL3, 8, 9, 10, 14, and 17 were significantly correlated with the prognosis of three cancers. CXCs were correlated with six types of immuno-infiltrating cells in three cancers. Immunohistochemistry of clinical samples confirmed that the expression of CXCL8 and 10 was higher in three cancer tissues. Animal experiments have shown that intestinal flora dysregulation can affect CXCL8 and 10 expressions. Our results further elucidate the function of CXCs in cancers and provide new insights into the prognosis and immune infiltration of breast, colon, and pancreatic cancers, and they suggest that intestinal flora may influence disease progression through CXCs.
| S-EPMC8392715 | biostudies-literature
Project description:BackgroundThe mRNA expression of protein Up-Frameshift Suppressor 3 Homolog B (UPF3B) differ in different tumors. However, the clinical relevance of UPF3B in cancer patients, such as with prognosis, tumor stage, and levels of tumor-infiltrating immune cells remain unclear.MethodsWe performed bioinformatics analysis of UPF3B with The Cancer Genome Atlas (TCGA) database (https://xenabrowser.net) and TIMER2.0 (Tumor Immune Estimation Resource 2.0, http://timer.comp-genomics.org/). UPF3B expression in 33 cancers versus counterpart normal tissues was analyzed using TCGA pan-cancer data. The influence of UPF3B in long-term prognosis was evaluated using Kaplan-Meier method, and the associations between UPF3B transcription levels and immune-related gene expression, immune cell infiltration, tumor microenvironment (TME) score are analyzed by spearman correlation analysis. Enrichment analysis of UPF3B was conducted using the R package "clusterProfiler."ResultsThe transcriptional level of UPF3B was dysregulated in the human pan-cancer dataset. A significant correlation was found between the expression of UPF3B and the pathological stage of Esophageal Carcinoma (ESCA), Kidney Chromophobe (KIHC), Liver Hepatocellular Carcinoma (LIHC), and Skin Cutaneous Melanoma (SKCM). Multiple cancer types with high transcriptional levels of UPF3B were associated with a significantly worse prognosis. The functions of expressed UPF3B gene are primarily related to ubiquitin mediated proteolysis, cell cycle, and mRNA surveillance pathway. Our results also show that immune cells infiltration and immunosuppressive markers such as CTLA-4, PD-1 and PD-L1 significantly correlate with UPF3B expression.ConclusionsIn the present study, we synthetically explored the expression status and prognostic significance of UPF3B, and the relationship with clinic characters and immune microenvironment across cancers. Our results may provide novel insights for UPF3B as an immunotherapeutic target and valuable prognostic biomarker in various malignant tumor.
| S-EPMC9531787 | biostudies-literature
Project description:C-C motif chemokine ligand 14 (CCL14) is a chemokine promoting the activation of immune cells. However, the relationship between CCL14 expression, tumor immunity, and prognosis in Hepatocellular Carcinoma (HCC) remain unclear. CCL14 expression and its influence on tumor prognosis were analyzed by the ONCOMINE, Tumor Immune Estimation Resource (TIMER) and Kaplan-Meier plotter. The relationship between CCL14 expression and tumor immunity were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). CCL14 expression was significantly lower in several human cancers, including HCC, than in corresponding normal tissues. CCL14 expression in HCC tissues correlated with prognosis. Low CCL14 expression associated with poorer overall survival, disease-specific survival, progression-free survival, and relapse-free survival in multiple cohorts of HCC patients, particularly at early disease stages (stage 1+2 or grade 2). CCL14 showed strong correlation with tumor-infiltrating B cells, CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells. CCL14 expression in HCC negatively correlated with expression of several immune cell markers, including exhausted T cell markers, PD-1, TIM-3 and CTLA-4, suggesting its role in regulating tumor immunity. These findings demonstrate that CCL14 is a potential prognostic biomarker that determines cancer progression and correlated with tumor immune cells infiltration in HCC.
| S-EPMC6977663 | biostudies-literature
Project description:BackgroundGlucose-6-phosphate isomerase (GPI) plays an important role in glycolysis and gluconeogenesis. However, the role of GPI in lung adenocarcinoma (LUAD) remains unclear.MethodsAll original data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated via R 3.2.2. GPI expression was explored with TCGA, GEO, and Oncomine databases. Immunohistochemistry staining was used to analyze GPI expression in clinical specimens. The correlations between GPI and cancer immune characteristics were analyzed via the TIMER and TISIDB databases. GPI-specific siRNAs were used to verify the role of GPI expression on cell proliferation and cell cycle distribution.ResultsIn general, GPI is predominantly overexpressed and has reference value in the diagnosis and prognostic estimation of LUAD. Upregulated GPI was associated with poorer overall survival, clinical stage, N stage, and primary therapy outcome in LUAD. Mechanistically, we identified a hub gene that included a total of 56 GPI-related genes, which were tightly associated with the cell cycle pathway in LUAD patients. Knockdown of GPI induced cell proliferation inhibition and cell cycle arrest. GPI expression was positively correlated with infiltrating levels of Th2 cells and regulatory T cells (Tregs); in contrast, GPI expression was negatively correlated with infiltrating levels of CD8+ T cells, central memory T cells, dendritic cells, macrophages, mast cells, and eosinophils. GPI was negatively correlated with the expression of immunostimulators, such as CD40L, IL6R, and TMEM173, in LUAD.ConclusionGPI may play an important role in the cell cycle and can be used as a prognostic biomarker for determining the prognosis and immune infiltration in LUAD.
| S-EPMC8666546 | biostudies-literature
Project description:Abnormal proline-rich protein 11 (PRR11) expression is associated with various tumors. However, there are few reports concerning PRR11 with prognostic risk, immune infiltration, or immunotherapy of bladder urothelial carcinoma (BLCA). This study is based on online databases, such as Oncomine, GEPIA, HPA, LinkedOmics, TIMER, ESTIMATE and TISIDB, and BLCA data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus, we employed an array of bioinformatics methods to explore the potential oncogenic roles of PRR11, including analyzing the relationship between PRR11 and prognosis, tumor mutational burden (TMB), microsatellite instability, and immune cell infiltration in BLCA. The results depict that PRR11 is highly expressed in BLCA, and BLCA patients with higher PRR11 expression have worse outcomes. In addition, there was a significant correlation between PRR11 expression and TMB and tumor immune infiltration. These findings suggest that PRR11 can be used as a potential marker for BLCA patient assessment and risk stratification to improve clinical prognosis, and its potential regulatory mechanism in the BLCA tumor microenvironment and targeted therapy is worthy of further investigation.
| S-EPMC9899238 | biostudies-literature
Project description:SNHG10 is a long non-coding RNA (lncRNA) found to be overexpressed in multiple human cancers including prostate cancer (PC). However, the underlying mechanisms of SNHG10 driving the progression of PC remains unclear. In this study, we investigated the role of SNHG10 in PC and found that SNHG10 expression was significantly increased in datasets extracted from The Cancer Genome Atlas. Increased expression of SNHG10 was related to advanced clinical parameters. Receiver operating curve analysis revealed the significant diagnostic ability of SNHG10 (AUC = 0.805). In addition, immune infiltration analysis, and GSEA showed that SNHG10 expression was correlated with oxidative phosphorylation and immune infiltrated cells. Finally, we determined that SNHG10 regulated cell proliferation, migration, and invasion of PC in vitro. In conclusion, our data demonstrated that SNHG10 was correlated with progression and immune infiltration, and could serve as a prognostic biomarker for PC.
| S-EPMC8523833 | biostudies-literature
Project description:Background The underlying functions and mechanisms of the Th17 pathway in Head and neck squamous cell carcinoma (HNSCC) progression and tumor immunology are still unclear. We investigated the correlation between IL17A expression and certain clinical parameters, tumor-infiltrating immune cells (TIICs) in TCGA HNSCC samples. Methods HNSCC files from the TCGA database were analyzed to obtain data on immune system infiltrates, gene expression, and related clinical information. R (Version 3.6.3) software, GEPIA, and TIMER online analysis tools were used to profile the relationship between the expression of IL17A and the prognosis, clinical stages, survival status and immune cell tumor-infiltrating levels of HNSCC patients. GEPIA and TIMER online analysis tools were used to verify the data. Results The expression of IL17A was significantly decreased in tumor tissues from HNSCC. IL17A expression was associated with M, N stage, lymphovascular invasion, and patients OS event. GSEA revealed that IL17A was closely related to humoral immune response, T cells response, and cytokine signal. TCGA database and TIMER online analysis indicated that the B cells and T cells levels were correlated with IL17A. The correlation between IL17A expression and correlated genes was analyzed. Conclusions IL-17A plays a key role in HNSCC. The levels of IL17A are important values for the determination of the occurrence and development of the HNSCC. The IL17A and correlated genes may be potential immunotherapeutic targets for HNSCC. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02703-1.
| S-EPMC9330648 | biostudies-literature