Prognostic and Immunological Role of Key Genes of Ferroptosis in Pan-Cancer
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ABSTRACT:
SUBMITTER: Shi Z
PROVIDER: S-EPMC8548644 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The family with sequence similarity 20-member C (Fam20C) kinase plays important roles in physiopathological process and is responsible for majority of the secreted phosphoproteome, including substrates associated with tumor cell migration. However, it remains unclear whether Fam20C plays a role in cancers. Here, we aimed to analyze the expression and prognostic value of Fam20C in pan-cancer and to gain insights into the association between Fam20C and immune infiltration. We analyzed Fam20C expression patterns and the associations between Fam20C expression levels and prognosis in pan-cancer via the ONCOMINE, TIMER (Tumor Immune Estimation Resource), PrognoScan, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan-Meier Plotter databases. After that, GEPIA and TIMER databases were applied to investigate the relations between Fam20C expression and immune infiltration across different cancer types, especially BLCA (bladder urothelial carcinoma), LGG (brain lower grade glioma), and STAD (stomach adenocarcinoma). Compared with adjacent normal tissues, Fam20C was widely expressed across many cancers. In general, Fam20C showed a detrimental role in pan-cancer, it was positively associated with poor survival of BLCA, LGG, and STAD patients. Specifically, based on TCGA (The Cancer Genome Atlas) database, a high expression level of Fam20C was associated with worse prognostic value in stages T2-T4 and stages N0-N2 in the cohort of STAD patients. Moreover, Fam20C expression had positive associations with immune infiltration, including CD4+ T cells, macrophages, neutrophils, and dendritic cells, and other diverse immune cells in BLCA, LGG, and STAD. Fam20C may serve as a promising prognostic biomarker in pan-cancer and has positive associations with immune infiltrates.
| S-EPMC7786334 | biostudies-literature
Project description:ObjectivesCLEC10A is expressed in a variety of cells, involved in a variety of biological pathways including immune response, and is closely related to the development of tumor immune response. However, the role of CLEC10A from a pan-cancer perspective has not yet been analyzed, and its role in human cancer prognosis and immunology remains largely unclear.MethodsWe studied the expression levels of CLEC10A and investigated its prognostic value in various cancers across distinct datasets including Oncomine, cBioPortal, and TCGA, and conducted immunohistochemical experiments using fresh bladder cancer and breast cancer samples to verify the results. In addition, we also performed GSEA of CLEC10A and explored the relationship between CLEC10A expression and immune infiltration, immune checkpoints, immune activation genes, immunosuppressive genes, chemokines and chemokine receptors.ResultsThe results showed that the expression level of CLEC10A in most tumors was significantly lower compared with non-cancerous tissue, and the decreased expression was related to poor prognosis and more advanced cancer stages. We also found that the expression of CLEC10A was significantly related to the immunomodulatory interaction between lymph and non-lymphocytes. Furthermore, the expression of CLEC10A was not only significantly correlated with the level of infiltration of CD4+T cells and CD8+T cells, but also closely related to immune checkpoints, immune activation genes, immunosuppressive genes, chemokines, and chemokine receptors. Importantly, our analysis of the relationship between CLEC10A and TMB and MSI also confirmed the speculation that CLEC10A may influence antitumor immunity by regulating the composition and immune mechanisms of the tumor microenvironment.ConclusionsIn conclusion, CLEC10A may serve as a new target for tumor immunotherapy and has great potential as a molecular biomarker for predicting pan-cancer prognosis and immune infiltration.
| S-EPMC9185031 | biostudies-literature
Project description:Despite accumulating cell- or animal-based experiments providing the relationship between Gasdermin E (GSDME) and human diseases, especially in malignant cancers, no pan-cancer analysis about the function of GSMDE in cancer management can be available up to date. Our research, for the first time, explored the potential carcinogenic role of GSDME across 33 tumors from the public platform of TCGA (The cancer genome atlas) database. GSDME is highly expressed in most malignant cancers, and obvious relationship exists between GSDME level and survival prognosis of cancer patients. The expression of GSDME was statically associated with the cancer-associated fibroblast infiltration in diverse cancer types, such as BLCA, CHOL, GBM, KIRC, LIHC, MESO, STAD, and UCEC. Furthermore, pyroptosis, sensory perception of sound, and defense response to bacterium were involved in the functional mechanisms of GSDME expression from GO analysis. Last but not the least, in vitro experiments were also performed to identify GSDME-induced pyroptosis. Our first pan-cancer analysis of GSDME not only broadens the understanding of the carcinogenic roles of GSDME but also provides a promising therapeutic strategy for benefiting an increasing number of cancerous patients based on GSDME-induced pyroptosis.
| S-EPMC8350383 | biostudies-literature
Project description:Recently some evidence has demonstrated the significance of PSMB8 in various malignancies. Nevertheless, PSMB8 (proteasome subunit beta 8), more familiar in the field of immunology contributing to the process of antigen presentation, is indeterminate in the role as a survival predictor of human pan-cancer. Besides, how PSMB8 interacts with immune cell infiltration in the tumor microenvironment requires further research. We then penetrated into the analysis of the PSMB8 expression profile among 33 types of cancer in the TCGA database. The results show that overexpression of PSMB8 was associated with poor clinical outcomes in overall survival (Sartorius et al. in Oncogene 35(22):2881-2892, 2016), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in most cancer varieties. In addition, there existed distinctly positive correlations between PSMB8 and immunity, reflected straightforwardly in the form of immune scores, tumor-infiltrating immune cells (TIICs) abundance, microsatellite instability, tumor mutation burden, and neoantigen level. Notably, specific markers of dendrite cells exhibited the tightest association with PSMB8 expression in terms of tumor-related immune infiltration patterns. Moreover, gene enrichment analysis showed that elevated PSMB8 expression was related to multiple immune-related pathways. We finally validated the PSMB8 expression in our local breast samples via quantitative PCR assays and concluded that PSMB8 appeared to perform well in predicting the survival outcome of BRCA patients. These findings elucidate the pivotal role of the antigen presentation-related gene PSMB8, which could potentially serve as a robust biomarker for prognosis determination in multiple cancers.
| S-EPMC8516870 | biostudies-literature
Project description:Objective: APBB1IP is a Rap1-binding protein that mainly acts as a regulator of leukocyte recruitment and pathogen clearance through complement-mediated phagocytosis. However, the role of APBB1IP in tumor immunity remains unclear. This study was carried out to evaluate the prognostic landscape of APBB1IP in pan-cancer analysis and investigate the relationship between APBB1IP expression and immune infiltration. Methods: We explored the expression pattern and prognostic value of APBB1IP in pan-cancer analysis through Kaplan-Meier Plotter and multiple databases, including TCGA, Oncomine. We then assessed the correlation between APBB1IP expression and immune cell infiltration using the TIMER database. Furthermore, we identified the proteins that interact with APBB1IP and performed epigenetic and transcriptional analyses. Multivariate Cox regression analyses were applied to construct a prognostic model, which consisted of APBB1IP and its interacting proteins, based on the lung cancer cohorts from the Gene Expression Omnibus (GEO) database. Results: The expression of APBB1IP was correlated with the prognosis of several types of cancer. APBB1IP upregulation was found to be associated with increased immune cell infiltration, especially for CD8+ T cells, natural killer (NK) cells, and immune regulators. A link was found between APBB1IP and immune-related proteins including RAP1A/B, TLN1/2 and VCL in the interaction network. Conclusion: APBB1IP can serve as a prognostic biomarker in pan-cancer analysis. APBB1IP upregulation was correlated with increased immune-cell infiltration, and the expression APBB1IP in different tumors might be related to the tumor immune microenvironment.
| S-EPMC7738982 | biostudies-literature
Project description:Ribosomal proteins (RPs) play an important role in the overall stability, function, and integrity of ribosomes. Ribosomal protein L4 (RPL4), which is encoded by RPL4, is assumed to play different roles in different cancers due to the strong correlation between them. However, research based on the underlying mechanisms of this correlations is limited. Therefore, this study investigated the biological role of RPL4 in various cancers. The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to compare the differential expression of RPL4 in tumor and normal tissues. The Sangerbox database and Kaplan-Meier method were employed to assess RPL4's impact on the prognosis of pan-cancer. Analyses using the cBioPortal tool, Shiny Methylation Analysis Resource Tool (SMART), and MethSurv provided insights into the methylation and epigenetic alterations of RPL4. Gene enrichment analysis revealed that RPL4 is involved in ribosome biogenesis through multiple pathways, and its enrichment in signaling pathways directly or indirectly influence tumor development. Tumor Immune Single-cell Hub (TISCH) was used to analyze RPL4 expression levels and cellular functions in the tumor microenvironment. Tumor Immune Estimation Resource Database 2.0 (TIMER2.0) and Tumor-Immune System Interactions Database (TISIDB) tools revealed that RPL4 affected the immune infiltration potential of tumors. Furthermore, the application of the ROC mapper and CellMiner databases indicated an association between RPL4 and sensitivity to multiple antitumor drugs. Additionally, RPL4 was found to remodel the tumor immune microenvironment, leading to the development of chemoresistance. In conclusion, the findings suggest that RPL4 can be used as a potential tumor biomarker and may serve as a target for immunotherapy in various cancers. Genetic testing of RPL4 provides a foundation for the diagnosis, prognosis, and treatment of clinical tumors.
| S-EPMC11305218 | biostudies-literature
Project description:ObjectivesOur previous studies revealed the significant roles of FK506-binding protein 4 (FKBP4) in tumorigenesis, however, there has been no pan-cancer analysis of FKBP4. Using bioinformatics, the current study reported the expression and prognostic role of FKBP4, and the correlation between FKBP4 and clinicopathological parameters, methylation, molecular network, immunological traits and drug sensitivity.MethodsRNA sequencing data, somatic mutation, and related clinical information were obtained from TCGA using UCSC Xena. The association between FKBP4 expression and clinical features was assessed using TISIDB. The relationships between FKBP4 expression and tumour stage, OS, DSS, DFS, and PFS were analysed using univariate cox regression analysis. The radar plots for TMB and MSI were obtained using "Fmsb" R package. UALCAN was used to explore the effect of FKBP4 methylation on tumour and normal samples. CBioportal was used to analyse copy number mutations in FKBP4 Gene expression and drug sensitivity data were downloaded from the CellMiner database. GO analysis was performed for the high and the low expression of FKBP4 compared with the median level of FKBP4 using clusterProfiler4.0.ResultsFKBP4 expression is significantly upregulated in various types of cancers. Cox regression analysis showed that high FKBP4 levels were correlated with poor OS, DSS, DFS, and PFS in most patients with cancer. Methylation of FKBP4 DNA was upregulated in most cancers, and FKBP4 expression is positively associated with transmethylase expression. FKBP4 and its copy were significantly associated with the expression of immune-infiltrating cells, immune checkpoint genes, immune modulators, TMB, MMR, and MSI. FKBP4 expression levels significantly correlated with 16 different drug sensitivities (all p < 0.05).ConclusionsOur pan-cancer bioinformatic analysis revealed a potential mechanism underlying the effects of FKBP4 on the prognosis and progression of various cancers.
| S-EPMC11004885 | biostudies-literature
Project description:Progestin and adipoQ receptor family member 4 (PAQR4) is a protein-coding gene. Recent studies have shown that PAQR4 is related to the development of multiple cancers. However, there is no systematic pan-cancer analysis of this gene. In this study, the expression of PAQR4, correlations with clinical prognosis, immune situation, and its potential molecular functions and mechanisms in pan-cancer were explored by bioinformatics analysis. The Cancer Genome Atlas was applied to investigate the relations between PAQR4 and clinical features, prognostic effects, and tumor immune microenvironment. R software was used to perform statistical analysis and figure creation. The expression of PAQR4 in BLCA and KIRC was validated by qRT-PCR and immunohistochemistry, and its function was explored by cellular experiments. Bioinformatics analysis revealed that PAQR4 was up-regulated in multiple cancers and related to poor prognosis. The high expression of PAQR4 was closely associated with high tumor stage, immune cell infiltration, tumor mutation burden, and microsatellite instability in different cancer types. In addition, the high expression of PAQR4 also indicated involvement in the immune regulatory pathways. The involvement of PAQR4 in the immune regulation of different tumors was confirmed by GSEA enrichment analysis. Moreover, PAQR4 was highly expressed in bladder cancer and renal clear cell carcinoma tissues and cell lines. Cell proliferation, migration, and invasion of bladder cancer and renal clear cell carcinoma cell lines were significantly decreased after the knockdown of PAQR4. This study elucidated the role of PAQR4 in carcinogenesis as well as tumor immunity. PAQR4 may serve as a potential prognostic biomarker in a variety of cancers.
| S-EPMC9732355 | biostudies-literature
Project description:Background: Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) was a kind of extracellular matrix glycoprotein. SPARCL1 was strongly inhibited in most cancers. However, the potential functions of SPARCL1 in the pan-cancer cohort have not been widely studied. Methods: We evaluated the transcriptional level and the prognostic value of SPARCL1 in 33 types of cancer and revealed the relationship between genetic alterations of SPARCL1 and the tumor mutation burden. Meanwhile, we assessed the correlations between SPARCL1 and tumor-infiltrating lymphocytes across cancers. Results: The transcriptional level of SPARCL1 was inhibited in most cancers. Although SPARCL1 was down-regulated in most cancers, SPARCL1 might play a protective or detrimental role in different cancers. We demonstrated that mutation count was elevated in the altered SPARCL1 group in several cancers. Additionally, we found a significant positive correlation between SPARCL1 and macrophage infiltration levels in most cancers. Especially, marker sets of M2 macrophages were strongly related to SPARCL1 in cholangiocarcinoma, colon adenocarcinoma, rectum adenocarcinoma, and pancreatic adenocarcinoma. Conclusion: Our study found that SPARCL1 might work as a biomarker for prognosis and immune infiltration in pan-cancer analysis.
| S-EPMC9722748 | biostudies-literature
Project description:Anillin actin-binding protein (ANLN) is crucially involved in cell proliferation and migration. Moreover, ANLN is significantly in tumor progression in several types of human malignant tumors; however, it remains unclear whether ANLN acts through common molecular pathways within different tumor microenvironments, pathogeneses, prognoses and immunotherapy contexts. Therefore, this study aimed to perform bioinformatics analysis to examine the correlation of ANLN with tumor immune infiltration, immune evasion, tumor progression, immunotherapy, and tumor prognosis. We observed increased ANLN expression in multiple tumors, which could be involved in tumor cell proliferation, migration, infiltration, and prognosis. The level of ANLN methylation and genetic alteration was associated with prognosis in numerous tumors. ANLN facilitates tumor immune evasion through different mechanisms, which involve T-cell exclusion in different cancer types and tumor-infiltrating immune cells in colon adenocarcinoma, kidney renal clear cell carcinoma, liver hepatocellular carcinoma, and prostate adenocarcinoma. Additionally, ANLN is correlated with immune or chemotherapeutic outcomes in malignant cancers. Notably, ANLN expression may be a predictive biomarker for the response to immune checkpoint inhibitors. Taken together, our findings suggest that ANLN can be used as an onco-immunological biomarker and could serve as a hallmark for tumor screening, prognosis, individualized treatment design, and follow-up.
| S-EPMC9390797 | biostudies-literature