Low expression of NLRP1 is associated with a poor prognosis and immune infiltration in lung adenocarcinoma patients.
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ABSTRACT:
SUBMITTER: Shen E
PROVIDER: S-EPMC7993699 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Janus kinase 1 (JAK1) is a member of the JAK family, which plays an essential and non-redundant role in tumorigenesis. However, the potential role of JAK1 in immune infiltration and prognosis of lung adenocarcinoma (LUAD) remains unclear. The mRNA expression and methylation level of JAK1 in LUAD were examined using the Oncomine and The Cancer Genome Atlas (TCGA) databases, respectively. The correlations between JAK1 expression and its methylation level and clinicopathological parameters were analyzed. The Kaplan-Meier plotter database was used to evaluate the prognostic value of JAK1 in LUAD. The signaling pathways associated with JAK1 expression were identified by performing a GSEA. The CIBERSORT and TIMER databases were used to analyze the correlations between JAK1 and tumor-infiltrating immune cells. In addition, the JAK1 expression and proportion of immune cells in LUAD cell lines were analyzed. The JAK1 expression was remarkably decreased in patients with LUAD and significantly correlated with the clinical features of patients with LUAD. The JAK1 methylation level was increased and negatively correlated with its mRNA expression. A decrease in JAK1 expression was correlated with poor prognosis. The results of GSEA showed that cell adhesion, tumorigenesis, and immune-related signaling pathways were mainly enriched. JAK1 was positively associated with tumor-infiltrating immune cells, and the results of CIBERSORT analysis suggested that JAK1 was correlated with monotypes and M1 macrophages. The results of the TIMER database analysis confirmed that JAK1 was closely associated with the gene markers of M1 macrophages. Thus, JAK1 may serve as a potential prognostic biomarker in LUAD and is associated with immune infiltration.
| S-EPMC7880401 | biostudies-literature
Project description:BackgroundInterleukin 6 (IL6) is both a pleiotropic cytokine and an immune-related gene. Interleukin 6 receptor (IL6R) is the receptor for IL6. It may be closely connected to the development of lung cancer. This research aims to explore the prognostic value of IL6R and prevent overtreatment of patients with lung adenocarcinoma (LUAD).MethodsIn this study, the expression of IL6R in tumor tissues and surrounding tissues was first analyzed by immunohistochemistry in the Affiliated Hospital of Nantong University (NTU) cohort. Secondly, we downloaded information from The Cancer Genome Atlas (TCGA) for the TCGA cohort and used this information to explore the messenger RNA (mRNA) level of IL6R. We then used Kaplan-Meier survival analyses, univariate and multivariate Cox analyses, nomogram models, and decision curve analyses to assess the prognostic value of IL6R. In addition, we also analyzed immune cell infiltration and the signaling pathways related to IL6R through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA).ResultsThrough the data analysis of the NTU cohort and the TCGA cohort, it was found that the expression of IL6R in normal tissues around the tumor was higher than that in tumor tissue, and was positively correlated with the overall survival (OS) of LUAD patients. Additionally, low expression of IL6R was found to be an independent predictor of poor prognosis among the patients in these two research cohorts. Next, using GO, KEGG, and GSEA analyses, we found that partially infiltrated tumor immune cells might be related to earlier staging and better prognosis of patients with LUAD. Finally, the study of the 3-5-year survival rate of LUAD patients through the nomogram showed that the expression of IL6R could improve the accuracy of prediction to prevent the overtreatment of some LUAD patients.ConclusionsIn summary, our study indicated that the low expression of IL6R was associated with poor prognosis among LUAD patients and that low expression of IL6R is a potential independent risk factor that could provide a basis for strengthening postoperative classification management of such patients.
| S-EPMC8339841 | biostudies-literature
Project description:BackgroundSperm-associated antigen 5 (SPAG5) has been identified as a novel driver oncogene involved in multiple cancers; however, its role in lung adenocarcinoma (LUAD) needs further investigation. Our study aims to elucidate the potential significance of SPAG5 in LUAD prognosis and its implications for the efficacy of immunotherapy.MethodsIn this study, we used bioinformatics analysis and tissue microarray (TMA) staining to examine the potential role of SPAG5 in LUAD survival and response to immunotherapy. We used the Oncomine, TIMER2.0, Gene Expression Profiling Interactive Analysis (GEPIA), Sangerbox, PredicScan, and Kaplan-Meier Plotter databases to examine the expression and prognostic role of SPAG5 in the LUAD of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other databases. We also used Cancer Single-cell State Atlas (CancerSEA) and Tumor Immune Estimation Resource (TIMER2.0) to analyze the association of SPAG5 with malignant phenotype and tumor immune microenvironment. Furthermore, Immune Cell Abundance Identifier (ImmuCellAI) analysis of TCGA sequencing data was used to predict the role of SPAG5 in determining the response to immune checkpoint blockade (ICB) treatment in LUAD. Co-expression analysis of programmed death-ligand 1 (PD-L1) and SPAG5 was performed using LUAD TMA immunohistochemistry (IHC) analysis.ResultsOur findings indicate that SPAG5 is overexpressed in LUAD and is positively correlated with advanced clinical stage, poor overall survival, relapse-free survival, and progression-free survival outcomes. SPAG5 may be involved in regulating the cell cycle, proliferation, invasion, DNA damage and repair, and tumor immunosuppression. Furthermore, TMA IHC analysis showed a positive correlation between PD-L1 expression in LUAD and SPAG5 which suggests that SPAG5 may serve as a potential predictor of response to ICB therapy in LUAD.ConclusionsOur results highlight the role of SAPG5 in promoting a tumor malignancy phenotype and immunosuppression in LUAD and suggest that SPAG5 may serve as a potential response marker for ICB therapy.
| S-EPMC10517604 | 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:The malignancy with the greatest global mortality rate is lung cancer. Lung adenocarcinoma (LUAD) is the most common subtype. The evidence demonstrated that voltage-gated potassium channel subunit beta-2 (KCNAB2) significantly participated in the initiation of colorectal cancer and its progression. However, the biological function of KCNAB2 in LUAD and its effect on the tumor immune microenvironment are still unknown. In this study, we found that the expression of KCNAB2 in tissues of patients with LUAD was markedly downregulated, and its downregulation was linked to accelerated cancer growth and poor clinical outcomes. In addition, low KCNAB2 expression was correlated with a deficiency in immune infiltration. The mechanism behind this issue might be that KCNAB2 influenced the immunological process such that the directed migration of immune cells was affected. Furthermore, overexpression of KCNAB2 in cell lines promoted the expression of CCL2, CCL3, CCL4, CCL18, CXCL9, CXCL10, and CXCL12, which are necessary for the recruitment of immune cells. In conclusion, KCNAB2 may play a key function in immune infiltration and can be exploited as a predictive biomarker for evaluating prognosis and a possible immunotherapeutic target.
| S-EPMC9653610 | biostudies-literature
Project description:A primary factor in tumor morbidity and mortality, lung adenocarcinoma (LUAD) is known to be a major subtype of lung cancer, having the lowest survival rate among all other cancers. Using The Cancer Genome Atlas (TCGA) database the relationship between the immune infiltrate and the NUP62CL was explored and the value of the NUP62CL expression in the prognosis and diagnosis LUAD was examined. Using the logistic regression and the Wilcoxon signed-rank test the relationship between the NUP62CL and the clinico-pathological features was analyzed. There was a significant correlation between the clinical stage (p = 0.005), the N (p = 0.004), and the decreased expression of NUP62CL. The prognosis of LUAD with high NUP62CL expression was revealed to be worse than that with low NUP62CL expression (p < 0.001) by the Kaplan-Meier survival analysis. The potentiality of NUP62CL to be a significant factor of prognosis for LUAD was indicated by the analyses of the multivariate and the univariate Cox regression models. In LUAD, the crucial role of recombination and maintenance of telomere as a significant pathway for NUP62CL was suggested by the Gene Set Enrichment Analysis (GSEA). To analyze the correlation between the genes and the tumor infiltrating immune cells the CIBERSORT was used. Moreover the positive correlation with the NUP62CL expression in LUAD of the infiltration level of the tumor infiltrating B lymphocytes and memory CD4+ T cells was exhibited by CIBERSORT. Therefore, NUP62CL may be a new valuable prognostic indicator for LUAD.
| S-EPMC8124116 | biostudies-literature
Project description:PurposeFSTL3 expression is altered in various types of cancer. However, the role and mechanism of action of FSTL3 in lung adenocarcinoma development and tumor immunity are unknown. We investigated the association between FSTL3 expression and clinical characteristics and immune cell infiltration in lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) and a separate validation set from our hospital.MethodsData on immune system infiltration, gene expression, and relevant clinical information were obtained by analyzing lung adenocarcinoma sample data from TCGA database. Using online tools like GEPIA, the correlations between FSTL3 expression and prognosis, clinical stage, survival status, and tumor-infiltrating immune cells were examined. In a validation dataset, immunohistochemistry was performed to analyze FSTL3 expression and its related clinical characteristics.ResultsFSTL3 expression was markedly reduced in patients with lung adenocarcinoma. N stage, pathological stage, and overall survival were significantly correlated with FSTL3 expression. According to GSEA, FSTL3 is strongly linked to signaling pathways such as DNA replication and those involved in cell cycle regulation. Examination of TCGA database and TIMER online revealed a correlation between FSTL3 and B cell, T cell, NK cell, and neutrophil levels. The prognosis of patients with lung adenocarcinoma was significantly affected by six genes (KRT6A, VEGFC, KRT14, KRT17, SNORA12, and KRT81) related to FSTL3.ConclusionFSTL3 is significantly associated with the prognosis and progression of lung adenocarcinoma and the infiltration of immune cells. Thus, targeting FSTL3 and its associated genes in immunotherapy could be potentially beneficial for the treatment of lung adenocarcinoma.
| S-EPMC10799152 | biostudies-literature
Project description:Background Hypoxia-inducible factor 1-alpha (HIF-1α) stability and transcriptional action are reduced by the hypoxia-inducible factor 1-alpha subunit suppressor (HIF1AN). Its inappropriate expression is associated with the development of cancer and immune control. It is yet unknown how HIF1AN, clinical outcomes, and immune involvement in breast cancer (BC) are related. Methods Using the GEPIA, UALCAN, TIMER, Kaplan-Meier plotter, and TISIDB datasets, a thorough analysis of HIF1AN differential expression, medical prognosis, and the relationship between HIF1AN and tumor-infiltrating immune cells in BC was conducted. Quantitative real-time PCR (qRT−PCR) analysis of BC cells were used for external validation. Results The findings revealed that, as compared to standard specimens, BC cells had significantly lower levels of HIF1AN expression. Good overall survival (OS) for BC was associated with higher HIF1AN expression. Additionally, in BC, the expression of HIF1AN was closely associated with the chemokines and immune cell infiltration, including neutrophils, macrophages, T helper cells, B cells, Tregs, monocytes, dendritic cells, and NK cells. A high correlation between HIF1AN expression and several immunological indicators of T-cell exhaustion was particularly revealed by the bioinformatic study. Conclusions HIF1AN is a predictive indicator for breast tumors, and it is useful for predicting survival rates.
| S-EPMC9932925 | biostudies-literature
Project description:Background: The expression of INMT (indolethylamine N-methyltransferase) has been reported to be downregulated in non-small-cell lung cancer (NSCLC). However, the role of INMT in NSCLC remains elusive. We aim to investigate the underlying mechanisms and clinical value of INMT in NSCLC, especially in lung adenocarcinoma (LUAD). Methods: Gene expression cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to assess the effect of INMT on NSCLC. Gene expression data from an immunotherapy cohort were used to investigate the association of INMT with immunotherapy in NSCLC. Results: INMT expression was significantly downregulated in NSCLC compared with adjacent normal tissues. Downregulated INMT was associated with poor overall survival in LUAD, but not in lung squamous carcinoma. Multivariate Cox regression analysis suggested that INMT was an independent prognostic marker in LUAD. INMT had a reference value in the diagnosis and prognostic estimation of LUAD. Gene set enrichment analysis showed that pathways of the cell cycle and DNA damage response were enriched in the INMT low-expression group. The top 10 hub genes upregulated in the INMT low-expression group mainly activated the cell cycle pathway. In addition, more frequently mutated TP53 genes, higher aneuploidy scores, a fraction of genomes altered, MANTIS scores, and tumor mutation burden were found in tumors with low expression of INMT. Furthermore, patients with low expression of INMT showed favorable clinical benefits to anti-PD-1 treatment with higher enrichment scores of immune-related signatures. Conclusion: The low expression of INMT was associated with poor prognosis but favorable immunotherapy response in LUAD. INMT may affect the progression of LUAD by regulating the cell cycle and may serve as a valuable independent prognostic biomarker in patients with LUAD.
| S-EPMC9686007 | biostudies-literature
Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis. More effective biomarkers and treatment options remain to be discovered. Mitotic Spindle Positioning (MISP), also called C19orf21, has been reported to be upregulated in several malignancies. However, the effects of MISP on PDAC have yet to be investigated.Materials and methodsThe differential expression of MISP at the mRNA and protein levels were evaluated using Gene Expression Profiling Interactive Analysis 2 (GEPIA 2), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) databases, and was further verified by quantitative real-time PCR and western blotting in PDAC cell lines. Correlations between MISP expression and clinical characteristics were explored using Kaplan-Meier Plotter Database and clinical data from The Cancer Genome Atlas (TCGA). CCK-8 assays, Transwell assays, and immunoblotting were used to determine the role of MISP in PDAC proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were executed by the R package 'clusterProfiler'. Correlations between MISP expression and immune cell infiltration, immune checkpoints, immunophenoscore (IPS) and the tumor mutational burden (TMB) in PDAC were explored using the R package 'CIBERSORT', the Tumor Immune Estimation Resource 2.0 (TIMER2.0), and The Cancer Immunome Atlas (TCIA) database based on TCGA data.ResultMISP expression was significantly higher in pancreatic cancer tissues compared to normal pancreas tissues, which was associated with a poor prognosis. Increased expression of MISP was related to the proliferation, migration and invasion of PDAC cell lines. GO and KEGG pathway analyses determined that MISP is involved in the Ras signaling pathway and immune regulation. Higher expression of MISP was associated with decreased infiltration levels of activated CD4+ memory T cells, CD8+ T cells, M2 macrophages and neutrophils. Furthermore, increased MISP was associated with lower expression of immune checkpoint molecules, higher gene mutation burden and IPS.ConclusionsThis study reveals that MISP, which is associated with the progression and prognosis of PDAC, may exert a potential regulatory effect on immune infiltration and predict the response to immunotherapy in PDAC.
| S-EPMC9005831 | biostudies-literature