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: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: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: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: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:Type 2 transmembrane serine protease (TMPRSS2) is a new member of the serine proteases, and studies have shown that TMPRSS2 plays a role in the occurrence of prostate malignancies and is closely related to the occurrence of the coronavirus disease 2019 (COVID-19). However, the role of TMPRSS2 in prostatic adenocarcinoma (PRAD) remains largely unclear. To better explore its function in PRAD, we examined the expression level of TMPRSS2 in the GEO, tumor immune assessment resource (TIMER), as well as Oncomine databases and studied the association between TMPRSS2 and overall survival (OS) rates in the UALCAN and gene expression profiling interactive analysis (GEPIA) databases. In addition, we studied the correlation of the level of immune infiltration and markers of immune cell type in the TIMER database, analyzed the prognosis based on the expression level of TMPRSS2 in the related immune cell subsets, and determined the methylation profile of TMPRSS2 promoter by UALCAN database. Subsequently, we conducted a survival analysis and gene ontology (GO) pathway analysis in the TISID database and detected the expression of TMPRSS2 in the Human Protein Atlas (HPA) database. We also studied the protein-protein interaction (PPI) network of TMPRSS2 in the GENEMANIA database. Additionally, we used the microarray GSE56677 and GSE52920 to illustrate changes in TMPRSS2 expression in vivo and in vitro after severe acute respiratory syndrome-coronavirus (SARS-COV) infection, finding that expression of TMPRSS2 decreased after SARS-COV infection in vitro. The function of TMPRSS2 in the dataset was further verified by gene set enrichment analysis (GSEA). In conclusion, the expression of TMPRSS2 is significantly increased in PRAD, elevated TMPRSS2 is associated with immune infiltration, and prognosis is positively correlated. In addition, tumor tissue from COVID-19 patients with PRAD may be more susceptible to infection with SARS-COV-2, which may render the prognosis gets worse.
| S-EPMC7556306 | biostudies-literature
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:Background: BTBD10 serves as an activator of Akt family members through decreasing the protein phosphatase 2A-mediated dephosphorylation. The present study attempted to investigate the prognostic value of BTBD10 in hepatocellular carcinoma (HCC), specially, its relationship with tumor-infiltrating lymphocytes (TILs). Methods: BTBD10 expression was evaluated in HCC using The Cancer Genome Atlas (TCGA) and Xijing Hospital database, and verified in HCC cell lines. Cox analyses were performed to analyze independent prognostic risk factors for HCC. The optimal cut-off value of BTBD10 was calculated, by which all patients were divided into two groups to compare the overall survival (OS). The signaling pathways were predicted, by which BTBD10 may affect the progression of HCC. To investigate the impact of BTBD10 on HCC immunotherapy, correlations between BTBD10 and TILs, immune checkpoints, m6A methylation-related genes and ferroptosis-related genes were assessed. The distribution of half-maximal inhibitory concentration (IC50) of diverse targeted drugs was observed based on the differential expression of BTBD10. Results: BTBD10 expression was higher in HCC tissues and cell lines than that of normal liver tissues and cells. The patients with high expression of BTBD10 showed a worse OS, as compared to that of BTBD10 low-expressing group. Cox analyses indicated that BTBD10 was an independent prognostic risk factor for HCC. Several molecular pathways of immune responses were activated in HCC patients with high-expressing of BTBD10. Furthermore, BTBD10 expression was demonstrated to be positively correlated with tumor-infiltrating B cells, T cells, macrophages, neutrophils and dendritic cells. Meanwhile, the expression of BTBD10 was synchronized with that of several m6A methylation-related genes, ferroptosis-related genes and immune checkpoints. The IC50 scores of Sorafenib, Navitoclax, Veliparib, Luminespib, and Imatinib were found to be lower in BTBD10 high-expressing HCC group. Conclusion: BTBD10 negatively regulates tumor immunity in HCC and exhibits adverse effect on the prognosis of HCC, which could be a potential target for immunotherapy.
| S-EPMC8764259 | biostudies-literature
Project description:BackgroundA preliminary study by our group revealed that the deficiency of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT) impaired regulatory T-cell differentiation in autoimmune hepatitis. Nevertheless, the prognostic value of EOGT in advanced hepatocellular carcinoma (HCC) and its relationship with immune infiltration remain obscured.MethodsInitially, EOGT expression was evaluated by Oncomine, TIMER, GEO, and UALCAN databases. Besides, the prognostic potential of EOGT expression was analyzed using GEPIA, Kaplan-Meier plotter, CPTAC, Cox regression, and nomogram in HCC samples. Furthermore, we investigated the association between EOGT expression and tumor mutation burden, DNA methylation, and immune infiltration in addition to its possible mechanism via cBioPortal, TIMER, GEPIA, ESTIMATE, CIBERSORT, GSEA, STRING, and Cytoscape.ResultsThe expression of EOGT in HCC was significantly higher than that in normal tissues. Additionally, elevated EOGT expression was correlated with advanced tumor staging and linked to poor overall survival and relapse-free survival, serving as a significant unfavorable prognostic indicator in HCC patients. Remarkably, our results revealed that high-EOGT expression subgroups with elevated TP53 or low CTNNB1 mutations have worse clinical outcomes than the others. Regarding immune infiltration, immunofluorescent staining showed that immune cells in HCC were positive for EOGT. Besides, elevated EOGT expression was linked to exhausted T cells and immune suppressor cells in HCC samples. More importantly, the proportion of CD8+ T cells was reduced in HCC samples with a high level of EOGT expression, but EOGT did not exhibit prognostic potential in HCC samples with increased CD8+ T cells.ConclusionsEOGT may hold great potential as a novel biomarker to distinguish prognosis and immune profiles of HCC patients.
| S-EPMC8766744 | biostudies-literature
Project description:Lung adenocarcinoma (LUAD) is one of the major types of lung cancer. Tumor-infiltrating immune cells (TIICs) are positively associated with overall survival (OS) in LUAD. The SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 2 (SPOCK2) is a complex type of secreted proteoglycan involved in forming a protective barrier against viral infection. The purpose of this study was to investigate the relationship between SPOCK2 and TIICs and the prognostic role of SPOCK2 in LUAD. The GEPIA2, GEO, CPTAC, and HPA databases were analyzed to examine both the mRNA and protein expression of SPOCK2 in LUAD. GEPIA2 and the Kaplan-Meier Plotter (KM Plotter) were used to evaluate the prognostic value of SPOCK2 in LUAD patients. TCGA data were examined for a correlation between SPOCK2 expression and clinical characteristics. Gene enrichment analyses were performed to explore the underlying mechanism of SPOCK2 based on LinkedOmics. RegNetwork was used to predict the regulators of SPOCK2. The correlation between SPOCK2 and TIICs, including immune infiltration level and relative proportion was investigated via TIMER. KM Plotter was also used to evaluate the prognostic role of SPOCK2 expression in LUAD with enriched and decreased TIIC subgroups. We found SPOCK2 was significantly downregulated in LUAD compared with that in non-tumor controls and was correlated with clinical parameters. Moreover, a high SPOCK2 expression level predicted better survival. The SPOCK2-associated regulatory network was constructed. SPOCK2 influenced the TIIC infiltration level and relative proportion in LUAD. Furthermore, a high SPOCK2 expression level was associated with a favorable prognosis in enriched CD4 + T cells and macrophage subgroups in LUAD. In conclusion, a high level of SPOCK2 expression predicted favorable prognosis and was significantly correlated with TIICs in LUAD. Therefore, the expression of SPOCK2 may affect the prognosis of LUAD partly due to TIICs.
| S-EPMC7683796 | biostudies-literature