CLEC10A is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in lung adenocarcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: He M
PROVIDER: S-EPMC8034442 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Overexpression of DARS2 may enhance the progression of hepatocellular carcinoma (HCC). However, there are few extensive reports on DARS2 function in lung adenocarcinoma (LUAD). The differential expression of DARS2 was detected by genomics and in vitro experiments, and the effect of DARS2 expression on LUAD cell activity was analyzed. Functional enrichment analysis was performed to explore possible signal pathways involved in the biological functions of DARS2 and its co-expressed genes. Utilizing TIMER and GEPIA datasets, the association between DARS2 expression and immunological infiltrating cells was analyzed. At the same time, the association between DARS2 expression pattern and LUAD m6A modification and cuproptosis was examined utilizing TCGA and GEO datasets. The level of DARS2 in LUAD increased, and inhibition of DARS2 expression could significantly inhibit the proliferation of LUAD cells. ROC curves showed that DARS2 overexpression could accurately diagnose LUAD and lead to a significant decline in the survival rates of OS, DSS, and PFI in LUAD. Enrichment analysis showed that DARS2 and its co-expressed genes were closely associated with chromosome segregation and the cell cycle. TIMER and GEPIA database analysis demonstrated that the DARS2 expression pattern was adversely correlated with the infiltration of B cells and Tfh cells. TCGA and GEO dataset examination revealed that DARS2 expression was significantly linked to four m6A-related genes and one cuproptosis-related gene. DARS2 expression is increased in LUAD patients and is closely associated with LUAD immune cell infiltration, modification of m6A, and cuproptosis. DARS2 is a potential reliable prognostic biomarker of LUAD.
| S-EPMC10077054 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD) with Pulmonary arterial hypertension (PAH) shows a poor prognosis. Detecting related genes is imperative for prognosis prediction.MethodsThe gene expression profiles of LUAD and PAH were acquired from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, respectively. The co-expression modules associated with LUAD and PAH were evaluated using the Weighted Gene Co-Expression Network Analysis (WGCNA). The relationship between key gene expression with immune-cell infiltration and the tumor immune microenvironment (TIME) was evaluated. We confirmed the mRNA and protein levels in vivo and vitro. G6PD knockdown was used to conduct the colony formation assay, transwell invasion assay, and scratch wound assay of A549 cells. EDU staining and CCK8 assay were performed on G6PD knockdown HPASMCs. We identified therapeutic drug molecules and performed molecular docking between the key gene and small drug molecules.ResultsThree major modules and 52 overlapped genes were recognized in LUAD and PAH. We identified the key gene G6PD, which was significantly upregulated in LUAD and PAH. In addition, we discovered a significant difference in infiltration for most immune cells between high- and low-G6PD expression groups. The mRNA and protein expressions of G6PD were significantly upregulated in LUAD and PAH. G6PD knockdown decreased proliferation, cloning, and migration of A549 cells and cell proliferation in HPASMCs. We screened five potential drug molecules against G6PD and targeted glutaraldehyde by molecular docking.ConclusionsThis study reveals that G6PD is an immune-related biomarker and a possible therapeutic target for LUAD and PAH patients.
| S-EPMC10817399 | biostudies-literature
Project description: Not available
| S-EPMC11231847 | biostudies-literature
Project description:TMPRSS2 is a transmembrane serine protease and plays a pivotal role in coronavirus disease 2019 (COVID-19). However, the correlation of TMPRSS2 with prognosis and immune infiltration in tumors has not yet been explored. Here, we analyzed the expression of TMPRSS2 in Oncomine and TIMER databases, the correlation between TMPRSS2 and overall survival in the PrognoScan, Kaplan-Meier plotter, and GEPIA databases. The association between TMPRSS2 and immune infiltration levels was investigated in the TIMER database. In addition, the prognosis of TMPRSS2 related to immune cells in cancers was analyzed. Quantitative real-time PCR (qRT-PCR) confirmed that TMPRSS2 was upregulated in lung adenocarcinoma (LUAD) and downregulated in breast invasive carcinoma (BRCA). We demonstrated that high TMPRSS2 expression was associated with favorable prognosis in LUAD, but it was associated with poor prognosis in BRCA. Interestingly, we found that TMPRSS2 expression was significantly correlated with immune infiltration of B cells, CD4+ T cells, macrophages, and dendritic cells in LUAD, and it was positively correlated with the infiltrating levels of CD8+ T cells, CD4+ T cells, neutrophils, and dendric cells in BRCA. Consistent with the prognosis of TMPRSS2 in LUAD and BRCA, the high expression level of TMPRSS2 has a favorable prognosis in enriched immune cells such as B cells, macrophages, and CD4+ T cells in LUAD, and it has a poor prognosis in CD4+ T cells and CD8+ T cells in BRCA. In conclusion, our results indicate that the prognosis of TMPRSS2 in LUAD and BRCA is significantly correlated with immune cells infiltration. Our study comprehensively revealed the relationship between the prognosis of TMPRSS2 in pan-cancers and tumor immunity.
| S-EPMC9086397 | biostudies-literature
Project description:BackgroundThe tumor microenvironment plays an important role in the occurrence and development of tumors. However, there are gaps in understanding the molecular and cellular interactions between tumor cells and the immune tumor microenvironment (TME). The aim of this study was to identify a novel gene that played an important role in the tumor microenvironment of lung adenocarcinoma (LUAD).MethodsThe gene expression profile and clinical data for LUAD were downloaded from TCGA database. First, we used the ESTIMATE algorithm to evaluate the immune and stromal scores accordingly. Also, we analyzed differentially expressed immune-related genes (IRGs) in the high and low immune/stromal score groups. Then, we used the protein-protein interaction network (PPI network) and a univariate Cox regression analysis to identify the hub gene. After that, we analyzed the relationship between CSF2RB expression and TNM stage/prognosis. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathway regulated by CSF2RB and the Pearson correlation analysis method was used to analyze the correlation between the CSF2RB and immune cells. Finally, we used Western blot, real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC) to validate CSF2RB expression in cancer and para-cancerous tissues.ResultsWe identified that CSF2RB played an important role in the tumor microenvironment of LUAD. The expression of CSF2RB in tumor tissues was lower than that in normal tissues. Furthermore, the Kaplan-Meier plotter showed that a low CSF2RB expression was associated with poor survival and multivariate COX regression analysis revealed that the CSF2RB gene was an independent risk factor for prognosis, independent of whether patients received chemotherapy or radiotherapy. More importantly, a high expression of CSF2RB was related to early T, N, and clinical stages. GSEA analysis revealed that CSF2RB associated with diverse immune-related pathways, including T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and B-cell receptor signaling pathway. CSF2RB expression levels were also positively related with the levels of infiltrating CD4+ T cells, macrophages, NK cells, and monocytes in LUAD. Finally, tumor tissues from LUAD patients were used for the assessment of CSF2RB expression. It was significantly lower in tumor sites than in adjacent normal tissues, which was consistent with data analysis.ConclusionCSF2RB effectively predicted the prognosis of patients with lung adenocarcinoma which could also be a potential target for cancer treatment and prevention. However, further studies are required to elucidate the function and regulatory mechanisms of CSF2RB and to develop some novel treatment strategies.
| S-EPMC9096117 | biostudies-literature
Project description:ObjectiveLung cancer (LC) is one of the top ten malignant tumors and the first leading cause of cancer-related death among both men and women worldwide. It is imperative to identify immune-related biomarkers for early LC diagnosis and treatment.MethodsThree Gene Expression Omnibus (GEO) datasets were selected to acquire the differentially expressed genes(DEGs) between LC and normal lung samples through GEO2R tools of NCBI. To identify hub genes, the DEGs were performed functional enrichment analysis, the protein-protein interaction (PPI) network construction, and Lasso regression. Then, a nomogram was constructed to predict the prognosis of patients with carcinoma based on hub genes. We further evaluated the influence of COL1A1 on clinical prognosis using GSE3141, GSE31210, and TCGA database. Also, the correlations between COL1A1 and cancer immune infiltrates and the B7-CD28 family was investigated via TIMER and GEPIA. Further analysis of immunohistochemistry shown that the COL1A1 expression level is positively correlated with CD276 expression level.ResultsBy difference analysis, there were 340 DEGs between LC and normal lung samples. Then, we picked out seven hub genes, which were identified as components of the risk signature to divide LC into low and high-risk groups. Among them, the expression of COL1A1 is highly correlated with overall survival(OS) and progression-free survival (PFS) (p < 0.05). Importantly, there is a moderate to strong positive relationships between COL1A1 expression level and infiltration level of CD4+ T cells, Macrophage, Neutrophil, and Dendritic cell, as well as CD276 expression level.ConclusionThese findings suggest that COL1A1 is correlated with prognosis and immune infiltrating levels, including CD4+ T cells, Macrophage, Neutrophil, and Dendritic cell, as well as CD276 expression level, indicating COL1A1 can be a potential immunity-related biomarker and therapeutic target in LC.
| S-EPMC8018245 | 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:Non-SMC condensin I complex subunit H (NCAPH) plays a regulatory role in various cancers. However, its role in prognosis and immune infiltrates in lung adenocarcinoma (LUAD) remains unclear. This study examined the expression of NCAPH in tumor tissues and its association with immune infiltrates and prognostic roles in LUAD patients. Patients characteristics were obtained from The Cancer Genome Atlas (TCGA). Integrated analysis of TCGA showed that NCAPH was overexpressed across cancers, including LUAD. NCAPH expression was verified by quantitative polymerase chain reaction and western blotting in 20 LUAD matched tissues. High NCAPH expression was significantly related to T, N, M, pathologic stage, primary therapy outcome and smoking status according to the Wilcoxon rank sum test. Cox and Kaplan-Meier analyses showed that the NCAPH-high group was associated with shorter OS. The PFI and DSS in the NCAPH-high group were significantly decreased. Multivariate analysis showed that NCAPH was an independent predictive factor for poor prognosis. Gene set enrichment analysis demonstrated that the G2/M checkpoint, ncRNA metabolic, memory B cells, KRAS, E2F targets and MIER1 process were significantly associated with NCAPH expression. Single-sample Gene Set Enrichment Analysis indicated that NCAPH expression was associated with levels of Th2 and mast cells. The impact of NCAPH on malignant phenotypes was evaluated by MTT, transwell, cell cycle and apoptosis assays in vitro. The malignant phenotype of LUAD cells was inhibited if NCAPH was knocked down. In conclusion, this research indicates that NCAPH could be a potential factor for predicting prognosis and a new biomarker in LUAD.
| S-EPMC9187691 | biostudies-literature
Project description:Colon adenocarcinoma (COAD) is one of the most serious cancers. It is important to accurately predict prognosis and provide individualized treatment. Evidence suggests that clinicopathological features and immune status of the body are related to the occurrence and development of cancer. Expression of long non-coding RNA (LncRNA) ALMS1 intronic transcript 1 (ALMS1-IT1) is observed in some cancer types, and we believe that it may have the potential to serve as a marker of COAD. Therefore, we used the data obtained from the cancer genome atlas (TCGA) database to prove the relationship between ALMS1-IT1 and COAD. Wilcoxon rank sum test, Chi-square test, Fisher exact test and logistic regression were used to evaluate relationships between clinical-pathologic features and ALMS1-IT1 expression. Receiver operating characteristic curves were used to describe binary classifier value of ALMS1-IT1 using area under curve score. Kaplan-Meier method and Cox regression analysis were used to evaluate factors contributing to prognosis. Gene oncology (GO) and (Kyoto Encyclopedia of Genes and Genomes) KEGG enrichment analysis were used to predict the function of differentially expressed genes associated with ALMS1-IT1. Gene set enrichment analysis (GSEA) was used to predict canonical pathways associated with ALMS1-IT1.Immune infiltration analysis was performed to identify the significantly involved functions of ALMS1-IT1. Starbase database was used to predict miRNAs and RNA binding proteins (RBPs) that may interact with ALMS1-IT1. Increased ALMS1-IT1 expression in COAD was associated with N stage (P < .001), M stage (P = .003), Pathologic stage (P = .002), and Primary therapy outcome (P = .009). Receiver operating characteristic curve suggested the significant diagnostic and prognostic ability of ALMS1-IT1 (area under curve = 0.857). High ALMS1-IT1 expression predicted a poorer overall-survival (P = .005) and poorer progression-free interval (PFI) (P = .012), and ALMS1-IT1 expression was independently correlated with PFI in COAD patients (hazard ratio (HR) :1.468; 95% CI: 1.029-2.093; P =.034) (HR: 1.468; 95% CI: 1.029-2.093; P = .034). GO, KEGG, GSEA, and immune infiltration analysis showed that ALMS1-IT1 expression was correlated with regulating the function of DNA and some types of immune infiltrating cells. ALMS1-IT1 expression was significantly correlated with poor survival and immune infiltrations in COAD, and it may be a promising prognostic biomarker in COAD.
| S-EPMC9592486 | biostudies-literature
Project description:BackgroundSLC7A7 (solute carrier family 7, amino acid transporter light chain, y + L system, member 7) is a critical gene in the regulation of cationic amino acid transport. However, the relationships between SLC7A7 and prognosis and tumor-infiltrating lymphocytes in different cancers remain unclear.MethodsSLC7A7 expression was analyzed using the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. The enrichment of the GO (Gene Oncology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was conducted by DAVID. We evaluated the influence of SLC7A7 on clinical prognosis using the PrognoScan database. The functional state of SLC7A7 in various types of cancers was analyzed by CancerSEA. The relationships between SLC7A7 and cancer immune infiltrates was investigated by TIMER. Furthermore, correlations between SLC7A7 expression and gene marker sets of immune infiltrates were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). The expression of SLC7A7 was verified by GEO database and immunohistochemistry.ResultsA lung cancer cohort study (GSE31210) showed that high SLC7A7 expression was associated with poor overall survival (OS) and relapse-free survival (RFS). In addition, SLC7A7 had a significant impact on the prognosis of diverse cancers. SLC7A7 expression was positively correlated with infiltrating levels of CD4 + and CD8 + T cells, macrophages, neutrophils and dendritic cells (DCs) in non-small cell lung cancer (NSCLC). SLC7A7 expression was also strongly correlated with various immune marker sets in NSCLC.ConclusionsThese results indicated a role for SLC7A7 in infiltration of CD8 + T cells, CD4 + T cells, tumor-associated macrophages (TAMs), neutrophils and DCs in multiple cancers, and regulation of T cell exhaustion and Tregs in NSCLC. These findings suggest that SLC7A7 could be served as a biomarker for prognosis and immune infiltration in NSCLC.
| S-EPMC7905560 | biostudies-literature