Corrigendum: NPM1 Is a Prognostic Biomarker Involved in Immune Infiltration of Lung Adenocarcinoma and Associated With m6A Modification and Glycolysis.
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ABSTRACT:
SUBMITTER: Liu XS
PROVIDER: S-EPMC8439576 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundOverexpression of NPM1 can promote the growth and proliferation of various tumor cells. However, there are few studies on the comprehensive analysis of NPM1 in lung adenocarcinoma (LUAD).MethodsTCGA and GEO data sets were used to analyze the expression of NPM1 in LUAD and clinicopathological analysis. The GO/KEGG enrichment analysis of NPM1 co-expression and gene set enrichment analysis (GSEA) were performed using R software package. The relationship between NPM1 expression and LUAD immune infiltration was analyzed using TIMER, GEPIA database and TCGA data sets, and the relationship between NPM1 expression level and LUAD m6A modification and glycolysis was analyzed using TCGA and GEO data sets.ResultsNPM1 was overexpressed in a variety of tumors including LUAD, and the ROC curve showed that NPM1 had a certain accuracy in predicting the outcome of tumors and normal samples. The expression level of NPM1 in LUAD is significantly related to tumor stage and prognosis. The GO/KEGG enrichment analysis indicated that NPM1 was closely related to translational initiation, ribosome, structural constituent of ribosome, ribosome, Parkinson disease, and RNA transport. GSEA showed that the main enrichment pathway of NPM1-related differential genes was mainly related to mTORC1 mediated signaling, p53 hypoxia pathway, signaling by EGFR in cancer, antigen activates B cell receptor BCR leading to generation of second messengers, aerobic glycolysis and methylation pathways. The analysis of TIMER, GEPIA database and TCGA data sets showed that the expression level of NPM1 was negatively correlated with B cells and NK cells. The TCGA and GEO data sets analysis indicated that the NPM1 expression was significantly correlated with one m6A modifier related gene (YTHDF2) and five glycolysis related genes (ENO1, HK2, LDHA, LDHB and SLC2A1).ConclusionNPM1 is a prognostic biomarker involved in immune infiltration of LUAD and associated with m6A modification and glycolysis. NPM1 can be used as an effective target for diagnosis and treatment of LUAD.
| S-EPMC8324208 | biostudies-literature
Project description:As an important member of the kindlin family, fermitin family member 1 (FERMT1) can interact with integrin and its aberrant expression involves multiple tumors. However, there are few systematic studies on FERMT1 in pancreatic carcinoma (PAAD). We used several public databases to analyze the expression level and clinicopathological characteristics of FERMT1 in PAAD. Meanwhile, the correlation between FERMT1 expression and diagnostic and prognostic value, methylation, potential biological function, immune infiltration, and sensitivity to chemotherapy drugs in PAAD patients were investigated. FERMT1 was significantly up-regulated in PAAD and correlated with T stage, and histologic grade. High FERMT1 expression was closely connected with poor prognosis and can be used to diagnose PAAD. Moreover, the methylation of six CpG sites of FERMT1 was linked to prognosis, and FERMT1 expression was significantly related to N6-methyladenosine (m6A) modification. Functional enrichment analysis revealed that FERMT1 co-expression genes participated in diverse biological functions including necroptosis. In addition, the expression of FERMT1 was associated with immune cell infiltration and the expression of immune checkpoint molecules. Finally, FERMT1 overexpression may be sensitive to chemotherapy drugs such as Palbociclib, AM-5992 and TAE-226. FERMT1 can serve as a diagnostic and prognostic marker of PAAD, which is connected with immune cell infiltration and the modulation of m6A and necroptosis.
| S-EPMC10048534 | biostudies-literature
Project description:BackgroundThe prognosis for patients with kidney renal clear cell carcinoma (KIRC) remains unfavorable, and the understanding of SRY-box transcription factor 11 (SOX11) in KIRC is still limited. The purpose of this paper is to explore the role of SOX11 in the prognosis of KIRC.MethodsWe analyzed SOX11 expression in KIRC and adjacent normal tissues using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Our study aims to establish a correlation between SOX11 expression and clinical pathological features. Differentially expressed genes (DEGs) were assessed using R software. Furthermore, we conducted Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA). Integration of data from the Tumor Immune Estimation Resource (TIMER) and TCGA databases allowed us to assess the association between SOX11 expression and immune infiltration in KIRC. Additionally, we analyzed the association between SOX11 gene expression and N6-methyladenosine (m6A) modification in KIRC using TCGA and GEO data.ResultsOur findings revealed high SOX11 expression in KIRC, which showed a significant correlation with tumor staging and prognosis. GO/KEGG and GSEA analyses indicated that SOX11 was closely associated with sodium ion transport, synaptic vesicle circulation, and oxidative phosphorylation. Analysis of the TIMER and TCGA databases demonstrated correlations of SOX11 expression levels with the presence of CD8+ T lymphocytes, neutrophils, CD4+ T cells, as well as B cells. Moreover, both the TCGA and GEO datasets showed a substantial association between SOX11 and m6A modification-related genes, namely ZC3H13, FTO, METTL14, YTHDC1, IGF2BP1, and IGF2BP2.ConclusionsSOX11 exhibits a correlation with m6A modification and immune infiltration, suggesting its potential as a prognostic biomarker for KIRC.
| S-EPMC11319951 | biostudies-literature
Project description:Background: Overexpression of solute carrier family 2 member 1 (SLC2A1) promotes glycolysis and proliferation and migration of various tumors. However, there are few comprehensive studies on SLC2A1 in colorectal cancer (CRC). Methods: Oncomine, The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases were used to analyze the expression of SLC2A1 in pan-cancer and CRC and analyzed the correlation between SLC2A1 expression and clinical characteristics of TCGA CRC samples. The expression level of SLC2A1 in CRC was certified by cell experiments and immunohistochemical staining analysis. The Genome Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses of SLC2A1 relative genes were completed by bioinformatics analysis. The correlation between SLC2A1 expression level and CRC immune infiltration cell was analyzed by Tumor IMmune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and TCGA database. The correlation between SLC2A1 expression level and ferroptosis and m6A modification of CRC was analyzed by utilizing TCGA and GEO cohort. Finally, the possible competing endogenous RNA (ceRNA) networks involved in SLC2A1 in CRC are predicted and constructed through various databases. Results: SLC2A1 is highly expressed not only in CRC but also in many other tumors. ROC curve indicated that SLC2A1 had high predictive accuracy for the outcomes of tumor. The SLC2A1 expression in CRC was closely correlated with tumor stage and progression free interval (PFI). GO, KEGG, and GSEA analysis indicated that SLC2A1 relative genes were involved in multiple biological functions. The analysis of TIMER, GEPIA, and TCGA database indicated that the SLC2A1 mRNA expression was mainly positively associated with neutrophils. By the analysis of the TCGA and GEO cohort, we identified that the expression of SLC2A1 is closely associated to an m6A modification relative gene Insulin Like Growth Factor 2 MRNA Binding Protein 3 (IGF2BP3) and a ferroptosis relative gene Glutathione Peroxidase 4 (GPX4). Conclusion: SLC2A1 can be used as a biomarker of CRC, which is associated to immune infiltration, m6A modification, ferroptosis, and ceRNA regulatory network of CRC.
| S-EPMC8987357 | biostudies-literature
Project description:N6-methyladenosine (m6A) RNA methylation plays a pivotal role in immune responses and the onset and advancement of cancer. Nonetheless, the precise impact of m6A modification in lung adenocarcinoma (LUAD) and its associated tumor microenvironment (TME) remains to be fully elucidated. Here, we distinguished distinct m6A modification patterns within two separate LUAD cohorts using a set of 21 m6A regulators. The TME characteristics associated with these two patterns align with the immune-inflamed and immune-excluded phenotypes, respectively. We identified 2064 m6A-related genes, which were used as a basis to divide all LUAD samples into three distinct m6A gene clusters. We applied a scoring system to evaluate the m6A gene signature of the m6A modification pattern in individual patients. To authenticate the categorization significance of m6A modification patterns, we established a correlation between m6A score and TME infiltration profiling, tumor somatic mutations, and responses to immunotherapy. A high level of m6A modification may be associated with the aggressiveness and poor prognosis of LUAD. Further studies should investigate the mechanism of action of m6A regulators and m6A-related genes to improve the diagnosis and treatment of patients with LUAD.
| S-EPMC10903232 | biostudies-literature
Project description:BackgroundRenal cell carcinoma (RCC) is the largest category of kidney tumors and usually does not have a good prognosis. N6-methyladenosine(m6A) and immune infiltration have received increased attention because of their great influence on the clinical outcome and prognosis of cancer patients.MethodsWe identified hub genes through multi-dimensional screening, including DEGs, PPI analysis, LASSO regression, and random forest. Meanwhile, GO/KEGG enrichment, cMAP analysis, prognostic analysis, m6A prediction, and immune infiltration analysis were performed to understand the potential mechanism and screen therapeutic drugs.ResultsWe screened 275 downregulated and 185 upregulated genes using three GEO datasets and the TCGA dataset. In total, 82 candidate hub genes were selected using STRING and Cytoscape. Enrichment analysis illustrated that the top 3 biological process terms and top 1 KEGG term were related to immunity. cMAP analysis showed some antagonistic molecules can be candidate drugs for the treatment of RCC. Then, six hub genes (ERBB2, CASR, P2RY8, CAT, PLAUR, and TIMP1) with strong predictive values for prognosis and clinicopathological features were selected. Meanwhile, P2RY8, ERBB2, CAT, and TIMP1 may obtain m6A modification by binding METTL3 or METTL14. On the other hand, differential expression of CAT, ERBB2, P2RY8, PLAUR, and TIMP1 affects the infiltration of the majority of immune cells.ConclusionsWe identified six hub genes through multi-dimensional screening. They all possess strong predictive value for prognosis and clinicopathological features. Meanwhile, hub genes may regulate the progression of RCC via an m6A- and immunity-dependent mechanism.
| S-EPMC9690957 | biostudies-literature
Project description:BackgroundThe biological function of distal-less homeobox 1 (DLX1) in lung adenocarcinoma (LUAD) remains unclear, despite a growing body of evidence that DLX1 is involved in the initiation and progression of various tumors.MethodsThis study explored and confirmed the prognostic and immunologic roles of DLX1 in LUAD via bioinformatic analysis and cellular functional validation. MethSurv was used to analyze the DNA methylation levels of DLX1 and the prognostic value of CpG islands. DLX1 mutation rates and prognoses between patients with and without the mutated DLX1 gene were analyzed by cBioPortal. Finally, cellular functional assays were used to investigate the effect of DLX1 on LUAD cells.ResultsOur results showed that DLX1 mRNA expression was significantly upregulated in LUAD. High DLX1 expression or promoter methylation was associated with worse prognosis, which confirmed DLX1 as an independent prognostic factor in LUAD. The level of multiple immune cell infiltration was significantly associated with DLX1 expression. Genes in the high DLX1 expression group were mainly enriched in cell cycle checkpoint, DNA replication, DNA repair, Fceri-mediated MAPK activation, TP53 activity regulation, and MET activation of PTK2-regulated signaling pathways. Cellular functional assays showed that the knockdown of DLX1 inhibited the proliferation, migration, and invasion of LUAD cells.ConclusionOur study identified DLX1 as a potential diagnostic and prognostic biomarker, and a promising therapeutic target in LUAD.
| S-EPMC10840498 | biostudies-literature
Project description:BackgroundColonic adenocarcinoma (COAD) is a common gastrointestinal tract tumor, and its occurrence and progression are typically associated with genomic instability, tumor-suppressor gene and oncogene mutations, and tumor mutational load. N6-methyladenosine (m6A) modification of RNAs and long non-coding RNA (lncRNA) expression are important in tumorigenesis and progression. However, the regulatory roles of m6A-associated lncRNAs in the tumor microenvironment, stratification of prognosis, and immunotherapy are unclear.MethodsWe screened 43 prognostic lncRNAs linked to m6A and performed consistent molecular typing of COAD using consensus clustering. The single-sample Gene Set Enrichment Analysis and ESTIMATE algorithms were used to assess the immune characteristics of different subgroups. Covariation between methylation-related prognostic lncRNAs was eliminated by least absolute shrinkage and selection operator Cox regression. A nomogram was created and evaluated by combining the methylation-related prognostic lncRNA model with other clinical factors. The relationship between the prognostic model grouping and microsatellite instability, immunophenotype score, and tumor mutation burden was validated using R scripts. Finally, we used a linkage map to filter sensitive medicines to suppress the expression of high-risk genes. Three m6A-associated lncRNA modes were identified in 446 COAD specimens with different clinical endpoints and biological statuses. Risk scores were constructed based on the m6A-associated lncRNA signature genes. Patients with lower risk scores showed superior immunotherapy responses and clinical benefits compared to those with higher risk scores. Lower risk scores were also correlated with higher immunophenotype scores, tumor mutation burden, and mutation rates in significantly mutated genes (e.g., FAT4 and MUC16). Piperidolate, quinostatin, and mecamylamin were screened for their abilities to suppress the expression of high-risk genes in the model.ConclusionsQuantitative assessment of m6A-associated lncRNAs in single tumors can enhance the understanding of tumor microenvironment profiles. The prognostic model constructed using m6A-associated lncRNAs may facilitate prognosis and immunotherapy stratification of patients with COAD; finally, three drugs with potential therapeutic value were screened based on the model.
| S-EPMC9909974 | biostudies-literature
Project description:BackgroundSolute carrier organic anion transporter family member 4A1 (SLCO4A1), a member of solute carrier organic anion family, is a key gene regulating bile metabolism, organic anion transport, and ABC transport. However, the association of SLCO4A1 with prognosis and tumor immune infiltration in colon adenocarcinoma (COAD) remains indistinct.MethodsFirstly, we explored the expression level of SLCO4A1 in COAD via GEPIA, Oncomine, and UALCAN databases. Secondly, we used the Kaplan-Meier plotter and PrognoScan databases to investigate the effect of SLCO4A1 on prognosis in COAD patients. In addition, the correlation between SLCO4A1 and tumor immune infiltration was studied by using TIMER and TISIDB databases.ResultsOur results showed that SLCO4A1 was overexpressed in COAD tissues. At the same time, our study showed that high expression of SLCO4A1 was associated with poor overall survival, disease-free survival, and disease-specific survival in COAD patients. The expression level of SLCO4A1 was negatively linked to the infiltrating levels of B cells, CD8+ T cells, and dendritic cells in COAD. Moreover, the expression of SLCO4A1 was significantly correlated with numerous immune markers in COAD.ConclusionsThese results indicated that SLCO4A1 could be associated with the prognosis of COAD patients and the levels of tumor immune infiltration. Our study suggested that SLCO4A1 could be a valuable biomarker for evaluating prognosis and tumor immune infiltration in COAD patients.
| S-EPMC10137198 | biostudies-literature
Project description:We analyzed the prognostic value of N6-methyladenosine (m6A) regulatory genes in lung adenocarcinoma (LADC) and their association with tumor immunity and immunotherapy response. Seventeen of 20 m6A regulatory genes were differentially expressed in LDAC tissue samples from the TCGA and GEO databases. We developed a five-m6A regulatory gene prognostic signature based on univariate and Lasso Cox regression analysis. Western blot analysis confirmed that the five prognostic m6A regulatory proteins were highly expressed in LADC tissues. We constructed a nomogram with five-m6A regulatory gene prognostic risk signature and AJCC stages. ROC curves and calibration curves showed that the nomogram was well calibrated and accurately distinguished high-risk and low-risk LADC patients. Weighted gene co-expression analysis showed significant correlation between prognostic risk signature genes and the turquoise module enriched with cell cycle genes. The high-risk LADC patients showed significantly higher PD-L1 levels, increased tumor mutational burden, and a lower proportion of CD8+ T cells in the tumor tissues and improved response to immune checkpoint blockade therapy. These findings show that this five-m6A regulatory gene signature is a prognostic biomarker in LADC and that immune checkpoint blockade is a potential therapeutic option for high-risk LADC patients.
| S-EPMC8064222 | biostudies-literature