SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma.
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ABSTRACT:
SUBMITTER: Yuan L
PROVIDER: S-EPMC8783894 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Tumor protein D52-like 2 (TPD52L2) belongs to the members of the TPD52 family. TPD52L2 was reported to regulate proliferation and apoptosis in cancer cells. However, its role in lung adenocarcinoma (LUAD) was uncertain. We evaluated the expression, methylation, copy number alteration, and prognostic significance of TPD52L2 using RNA-seq data from The Cancer Genome Atlas (TCGA). Enrichment analysis of TPD52L2 was conducted using the R package "clusterProfiler." We further assessed the association between TPD52L2 and immune cell infiltration level, immunosuppressive genes, and tumor mutational burden (TMB). The difference of gene mutant frequency in high- and low-TPD52L2 groups was also analyzed. The results showed that TPD52L2 was over-expressed and predicted worse survival status in LUAD. We also found that TPD52L2 expression was positively associated with the infiltration levels of immunosuppressive cells, such as regulatory T cells (Tregs) and tumor-associated macrophages (TAMs), and negatively correlated with immune killer cells, such as CD8+ T and NK cells in pan-cancer, including LUAD. In addition, TPD52L2 expression was associated with immunosuppressive genes and TMB. High expression of TPD52L2 was with more mutant frequency of TP53. In summary, our results show that TPD52L2 is an oncogene and a potential prognostic biomarker in LUAD. High TPD52L2 expression is a possible indicator of immune infiltration and associated with tumor immunosuppressive status in LUAD.
| S-EPMC8567320 | biostudies-literature
Project description:BackgroundGRAP2 is an adaptor protein involved in leukocyte signal activation; however, the prognostic value of GRAP2 and its correlation with immune infiltration in lung adenocarcinoma (LUAD) are unclear.MethodsOriginal data were downloaded from the TCGA database and Gene Expression Omnibus (GEO) database. GRAP2 expression was analyzed with the TCGA and TIMER databases. We evaluated the influence of GRAP2 on clinical prognosis using the Kaplan-Meier plotter, GEO, and GEPIA database. The TIMER and TISIDB databases were used to investigate correlations between GRAP2 expression and cancer immune characteristics. Finally, we confirmed the expression of GRAP2 in LUAD by immunohistochemistry staining.ResultsThe transcription levels of GRAP2 were significantly lower in several human cancer types, including LUAD, than in adjacent normal tissues. Immunohistochemistry staining confirmed that LUAD tumor tissues had lower GRAP2 protein expression levels than adjacent normal tissues. GRAP2 downregulation was associated with poorer overall survival, pathologic stage, T stage, N stage, and primary therapy outcome in LUAD. Mechanistically, we found a hub gene set that included a total of 91 genes coexpressed with GRAP2, which were closely related to the immune response in LUAD. The expression levels of GRAP2 were positively correlated with the infiltration levels of multiple immune cells and the cumulative survival time of a few immune cells. GRAP2 expression was found to be positively correlated with that of multiple immune markers, chemokines, chemokine receptors, and MHC molecules in LUAD.ConclusionsGRAP2 can be used as a biomarker for assessing prognosis and immune infiltration levels in LUAD.
| S-EPMC9701895 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD) is a common subtype of non-small cell lung cancer with high morbidity and mortality rates and is usually detected at advanced stages because of the early onset of metastasis. Adenosine deaminase RNA-specific 1 (ADAR1) is an RNA editing enzyme that catalyzes the important physiological process of adenosine-to-inosine editing and has been shown to participate in the progression of LUAD. Increasing evidence has suggested that immune infiltration of the tumor immune microenvironment has prognostic value for most human solid organ malignancies; however, much is unknown about the functions of ADAR1.MethodsThe expression of ADAR1 was analyzed in The Cancer Genome Atlas -LUAD database and validated in our LUAD cohort. To assess the prognostic value of ADAR1, Kaplan-Meier survival analyses and Cox regression analyses were carried out in LUAD cohorts. The association between ADAR1 and LUAD immune infiltrates via analyses of cell-type identification by estimating relative subsets of known RNA transcripts. Furthermore, multiplex immunohistochemistry was used to confirm the relationship between ADAR1 expression and immune cells in the present cohort of patients with LUAD.ResultsADAR1 was highly expressed in LUAD tissues and closely correlated with lymph node metastasis (LNM) (p < 0.01), advanced tumor stage (p < 0.05), and poor patient prognosis (p < 0.01), thus indicating that increased ADAR1 contributed to the progression of LUAD. LUAD with high ADAR1 expression can metastasize to lymph nodes that express more ADAR1 than the primary lesion. In addition, M0 macrophages and M2 macrophages increased and CD4+ T cells decreased in LUAD tissues with high ADAR1 expression. And the expression of ADAR1 in lymph node metastases was negatively correlated with the contents of CD4+ T cells (p = 0.0017) and M1 macrophages (p = 0.0037).ConclusionThe findings of our study suggested that ADAR1 may be useful in predicting prognosis and LNM in LUAD, and may serve as a promising immune-related molecular target for LUAD patients.
| S-EPMC10358204 | biostudies-literature
Project description:BackgroundTUBA1C is a microtubule component that is involved in a variety of cancers. Our main objective was to investigate TUBA1C expression, its prognostic value, its potential biological functions, and its impact on the immune system of patients with lung adenocarcinoma (LUAD).MethodsThe Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA) and Immunohistochemistry Analysis were used to analyze TUBA1C expression, its clinicopathology, overall survival (OS), and disease-free survival (DFS) in LUAD patients. We also determined the correlation between TUBA1C and tumor-infiltrating immune cells (TIICs) by using CIBERSORT and GEPIA databases. To determine the expression of TUBA1C in LUAD, we analyzed a collection of immune infiltration levels and cumulative survival of LUAD tissues in TIMER database. By using UALCAN, STRING, and GeneMANIA databases, we investigated the protein-coding genes related to TUBA1C and its co-expression genes in LUAD tissues. Gene set enrichment analysis (GSEA) was performed by using the TCGA dataset.ResultsThe mRNA and the protein expression of TUBA1C were found to be up-regulated in LUAD tissues. The univariate analysis indicated that an increased expression of TUBA1C was significantly correlated to the following parameters: age, stage, and lymph node metastasis. An over-expression of TUBA1C was associated with a poor prognosis of LUAD. In TIMER and CIBERSORT databases, we found that TUBA1C is correlated with 13 types of TIICs: activated B cell, activated CD4 T cell, central memory CD4 T cell, effector memory CD8 T cell, eosinophils, immature B cell, gamma-delta T cell, immature dendritic cell, mast cell, memory B cell, natural killer T cell, regulatory T cell, and type 2T helper cell. By performing GSEA, we found that TUBA1C is closely correlated to cell cycle, p53 signaling pathway, glycolysis, and gluconeogenesis.ConclusionsOur findings indicate that TUBA1C is associated with TIICs in tumor microenvironment. Therefore, it serves as a novel prognostic biomarker and a target for future treatment methods of LUAD.
| S-EPMC7923461 | biostudies-literature
Project description:Lung adenocarcinoma (LUAD) is the predominant subtype of lung cancer with a relatively poor prognosis. The dramatic improvements of new immunotherapy strategies have shown promising results in lung cancer patients. This study aimed to elucidate the functions of immune-associated genes in LUAD prognosis and pathogenesis by analyzing public databases. We obtained expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA) database and applied the ESTIMATE algorithm to calculate immune scores and stromal scores. A series of microenvironment-related genes with prognostic value was then identified. Of note, heat shock factor 5 (HSF5) was found to be decreased in LUAD patients and positively correlated with overall survival, which was further confirmed in the Gene Expression Omnibus (GEO) database. Moreover, Gene Ontology (GO) analysis based on the correlated genes of HSF5 demonstrated that HSF5 expression was significantly associated with the immune response and inflammatory activities. Based on the Tumor IMmune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) datasets, HSF5 expression showed strong correlations with various immune cell infiltration and diverse immune marker sets. These findings suggest that HSF5 can be used as a promising biomarker for determining prognosis and immune infiltration in LUAD patients.
| S-EPMC7757139 | 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:ObjectiveMesothelioma (MESO) is a rare tumor derived from mesothelium cells. The aim of this study was to explore key candidate genes and potential molecular mechanisms for mesothelioma through bioinformatics analysis.MethodsThe MESO expression profiles came from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The differences in the infiltration levels of immune cells between MESO and normal tissues were assessed using CIBERSORT. Differentially expressed genes (DEGs) were identified by comprehensive analysis of multiple datasets. A protein-protein interaction (PPI) network was constructed, and a hub gene COL1A1 was selected for MESO. The expression and mutation of COL1A1 in MESO were analyzed in the cBioPortal database. The correlation between COL1A1 expression and immune cell infiltration was evaluated using the TIMER database. Gene Set Enrichment Analysis (GSEA) of COL1A1 was then performed. Finally, Kaplan-Meier survival analysis was presented to predict the survival times between high and low COL1A1 expression groups for MESO patients.ResultsThere were distinct differences in the infiltration levels of immune cells between MESO and normal tissues. A total of 118 DEGs were identified by comprehensively analyzing three expression profile datasets. COL1A1, a hub gene, was identified to be highly expressed in MESO compared to normal tissues. COL1A1 genetic mutation occurred in 9% of MESO samples, and amplification was the most common type of mutation. COL1A1 expression was significantly correlated to the infiltration levels of CD4+ T cells, macrophages, and neutrophils. GSEA results indicated that COL1A1 could be involved in key biological processes and pathways like extracellular matrix and PI3K-Akt pathway. Patients with high COL1A1 expression usually experienced shorten overall survival time than those with its low expression.ConclusionOur findings revealed that COL1A1 could become a potential prognostic biomarker for MESO, which was significantly related to immune cell infiltration.
| S-EPMC7803428 | biostudies-literature
Project description:BackgroundGlucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a crucial enzyme involving hexosamine biosynthesis pathway and is upregulated in breast cancer (BRCA). However, its biological function and mechanism on patients in BRCA have not been investigated.MethodsIn this study, the differential expression of GNPNAT1 was analyzed between BRCA tissues and normal breast tissues using the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, which was validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. Then, the potential clinical value of GNPNAT1 in BRCA was investigated based on TCGA database. Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Variation Analysis, were performed to explore the potential signaling pathways and biological functions involved in GNPNAT1 in BRCA. Tumor immune infiltration was analyzed using ESTIMATE, CIBERSORT and TISIDB database; and immune therapy response scores were assessed using TIDE. Finally, Western blot, Cell counting kit-8 and Transwell assay were used to determine the proliferation and invasion abilities of breast cancer cells with GNPNAT1 knockdown.ResultsGNPNAT1 was up-regulated in BRCA tissues compared with normal tissues which was subsequently verified in different cell lines and clinical tissue samples. Based on TCGA and GEO, the overexpression of GNPNAT1 in BRCA contributed to a significant decline in overall survive and disease specific survive. Functional enrichment analyses indicated that the enriched pathways in high GNPNAT1 expression group included citrate cycle, N-glycan biosynthesis, DNA repair, and basal transcription factors. Moreover, the overexpression of GNPNAT1 was negatively correlated with immunotherapy response and the levels of immune cell infiltration of CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. Knockdown of GNPNAT1 impairs the proliferation and invasion abilities of breast cancer cells.ConclusionGNPNAT1 is a potential diagnostic, prognostic biomarker and novel target for intervention in BRCA.
| S-EPMC10195997 | biostudies-literature
Project description:Background ZC3H12 family members have an important role in tumorigenesis and development. However, the relationship between ZC3H12 family members and the prognosis of lung adenocarcinoma (LUAD) and tumor infiltrating lymphocytes is not clear. Methods The expression of ZC3H12 family members in LUAD was analyzed by UALCAN. UALCAN, Kaplan–Meier Plotter, and GEPIA were used to evaluate the effect of ZC3H12 family members on the prognosis of LUAD. The relationship between prognostic ZC3H12 family members and 14 functional states of LUAD was studied by CancerSEA. The correlation between ZC3H12 and immune cell infiltration was studied by TIMMER. In addition, the correlation between ZC3H12D expression and an immune infiltration gene marker set was analyzed by TISIDB and GEPIA. Finally, the expression of ZC3H12D in LUAD was further verified by the GEO database and immunohistochemical staining. Results The combined prognostic analysis of UALCAN, Kaplan-Meier Plotter, and GEPIA showed that the up-regulated expression of ZC3H12D mRNA was closely related to an improvement in overall survival rate (OS) in patients with LUAD. There was no significant correlation between ZC3H12D and 14 functional states of LUAD. Further analysis showed that the expression of ZC3H12D was positively correlated with the infiltration of B cells and CD4+T cells in LUAD. The expression of ZC3H12D was also positively correlated with immune markers in LUAD, including B cell-derived TNF and LTA cytokines, CXCL13, and its receptor CXCR5. Immunohistochemical staining showed that the expression of ZC3H12D in LUAD tissue samples was higher than normal lung tissues. Conclusions These findings suggest that multiple ZC3H12 family members are associated with the prognosis of patients with LUAD tumors. The increased expression of ZC3H12D was correlated with improved prognosis. ZC3H12D was shown to be associated with the level of immune cell infiltration, including B cells and CD4+T cells. Thus, ZC3H12D can be used as a biomarker to judge the prognosis and immune infiltration of LUAD.
| S-EPMC8798865 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD) is the most common malignant cancer in humans and because of low long-term survival rates, exploration of the molecular mechanisms underlying its progression, as well as novel prognostic predictors, is urgently needed. B3GNT3, a type II transmembrane protein located in the Golgi apparatus, is essential for forming extended core 1 oligosaccharides and is reportedly involved in malignant transformation.MethodsThe Cancer Genome Atlas (TCGA) and GSE68465 were used to analyze the expression of B3GNT3 in LUAD and normal tissues and overall survival. Real time quantitative polymerase chain reaction (qPCR) and western blot were conducted to measure the mRNA and protein levels of B3GNT3, respectively. Functional enrichment of differentially expressed genes was explored using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. We performed univariate and multivariate Cox regression analyses and a meta-analysis to reveal an independent factor for LUAD. We evaluated the correlation between immune infiltration levels and cumulative survival in the TIMER database. The correlation between B3GNT3 and immune cell infiltration was assessed via Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT). The association of DNA methylation of B3GNT3 and prognosis was determined. A nomogram that incorporated expression and clinical features was additionally built for prognostic prediction. Cell proliferation, cloning, and invasion were conducted to validate the roles of B3GNT3 in LUAD.ResultsB3GNT3 was more highly expressed in LUAD tissues than in normal lung tissues, consistent with the mRNA and protein levels in LUAD cells. B3GNT3 was an independent factor for LUAD. Moreover, the levels of B3GNT3 were related to immune cell infiltration in LUAD microenvironments. DNA methylation of B3GNT3 correlated with the mRNA of B3GNT and overall survival of LUAD patients. The expression of B3GNT3 was highly valuable for the prediction of diagnosis. Knockdown of B3GNT3 inhibited LUAD cell viability and cloning ability, and hindered invasion.ConclusionsB3GNT3 was highly associated with immune cell infiltration, acting as an important biomarker for the prognosis and diagnosis of LUAD.
| S-EPMC9011202 | biostudies-literature