Pan-Cancer Analysis Reveals FH as a Potential Prognostic and Immunological Biomarker in Lung Adenocarcinoma
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SUBMITTER: Zhang H
PROVIDER: S-EPMC8563123 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAnti-silencing function 1 (ASF1) is a conserved histone H3-H4 chaperone protein. ASF1B, a paralog of ASF1, acts by promoting cell proliferation and influencing cell cycle progression. Although there is some evidence demonstrating that ASF1B plays a key role in the development, progression, and prognosis of certain cancers, there are no pan-cancer analyses of ASF1B.MethodsWe used a range of bioinformatics approaches to investigate the predictive role of ASF1B, including its correlation with prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), and immune cell infiltration, in diverse cancer types.ResultsWe found that ASF1B was highly expressed in 22 cancers and was negatively correlated with the prognosis of multiple major cancer types. Furthermore, ASF1B expression was correlated with TMB in 21 cancers and with MSI in 7 cancers. We found that ASF1B was coexpressed with genes encoding immune activators, immune suppressors, major histocompatibility complexes, chemokines, and chemokine receptors. We further found that the role of ASF1B in the infiltration of different types of immune cells varied across tumor types. ASF1B may potentially affect several key immune-related pathways, such as those involved in antigen processing and presentation, natural killer cell-mediated cytotoxicity, and autoimmune thyroid disease.ConclusionsOur findings show that ASF1B may serve as a prognostic marker and potential immunotherapeutic target for several malignancies due to its role in tumorigenesis and immune infiltration.
| S-EPMC8495294 | biostudies-literature
Project description:BackgroundFurin is a calcium-dependent protease that processes various precursor proteins through diverse secretory pathways. The deregulation of FURIN correlated with the prognosis of patients in numerous diseases. However, the role of FURIN in human pan-cancer is still largely unknown.MethodsMultiple bioinformatic methods were employed to comprehensively analyze the correlation of FURIN expression with prognosis, mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB), DNA methylation, tumor immune infiltration, and common immune checkpoint inhibitors (ICIs) from the public database, and aim to evaluate the potential prognostic value of FURIN across cancers.ResultsFURIN was aberrantly expressed and was strongly correlated with MMR, MSI, TMB, and DNA methylation in multiple types of cancer. Moreover, survival analysis across cancers revealed that FURIN expression was correlated with overall survival (OS) in four cancers, disease-specific survival (DSS) in five cancers, progression-free interval (PFI) in seven cancers, and disease-free interval (DFI) in two cancers. Also, FURIN expression was related to immune cell infiltration in 6 cancers and ImmuneScore/StromalScore in 10 cancers, respectively. In addition, FURIN expression also showed strong association between expression levels and immune checkpoint markers in three cancers.ConclusionFURIN can serve as a significant prognostic biomarker and correlate with tumor immunity in human pan-cancer.
| S-EPMC8100462 | biostudies-literature
Project description:SLMO2 is a lipid transporter that transports phosphatidylserine to the interior of mitochondria, also known as PRELID3B, which plays an important role in lipid metabolism. It has also been reported to be involved in the growth process of breast and lung tumors. However, its functions and underlying mechanisms in cancer progress remain elusive, and the potential as pan-cancer biomarker and therapeutic target remains unexplored. Using the TCGA project and GEO database, we performed pan-cancer analysis of SLMO2, which including the expression pattern, prognostic value, mutation landscape, methylation modification, protein-protein interaction network and the relationship between SLMO2 expression and immune infiltration. KEGG enrichment analysis was also performed to predict function and relevant cellular pathways of SLMO2. In addition, proliferation and migration assays were performed to detect the proliferation and metastasis capacity of breast cancer and lung cancer cells. In our study, we found that SLMO2 was overexpressed in pan-cancer and the elevated expression of SLMO2 was correlated with poorer prognosis. SLMO2 mutations were distributed in a variety of tumors and correlated with prognosis. Promoter methylation analysis showed that SLMO2 methylation levels were lower in most tumors compared with normal tissues, while a few tumors showed increased methylation levels of SLMO2. SLMO2 expression was also positively correlated with immune infiltration of MDSCs. Further pathway enrichment analysis indicated that SLMO2 was involved in regulating of cytoplasmic transport and other oncogenic processes. In vitro experiments have shown that SLMO2 promotes the proliferation and migration of breast cancer and lung cancer cells. In conclusion, our findings suggested that SLMO2 was a potential prognostic and immunological marker in pan-cancer. This study suggested a potential strategy for targeting SLMO2 to treat tumors, including manipulating tumor growth or the tumor microenvironment, especially the infiltration of MDSC.
| S-EPMC10784594 | biostudies-literature
Project description:BackgroundBelonging to the protein arginine methyltransferase (PRMT) family, the enzyme encoded by coactivator associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of protein arginine residues, especially acts on histones and other chromatin related proteins, which is essential in regulating gene expression. Beyond its well-established involvement in the regulation of transcription, recent studies have revealed a novel role of CARM1 in tumorigenesis and development, but there is still a lack of systematic understanding of CARM1 in human cancers. An integrated analysis of CARM1 in pan-cancer may contribute to further explore its prognostic value and potential immunological function in tumor therapy.ResultsBased on systematic analysis of data in multiple databases, we firstly verified that CARM1 is highly expressed in most tumors compared with corresponding normal tissues, and is bound up with poor prognosis in some tumors. Subsequently, relevance between CARM1 expression level and tumor immune microenvironment is analyzed from the perspectives of tumor mutation burden, microsatellite instability, mismatch repair genes, methyltransferases genes, immune checkpoint genes and immune cells infiltration, indicating a potential relationship between CARM1 expression and tumor microenvironment. A gene enrichment analysis followed shortly, which implied that the role of CARM1 in tumor pathogenesis may be related to transcriptional imbalance and viral carcinogenesis.ConclusionsOur first comprehensive bioinformatics analysis provides a broad molecular perspective on the role of CARM1 in various tumors, highlights its value in clinical prognosis and potential association with tumor immune microenvironment, which may furnish an immune based antitumor strategy to provide a reference for more accurate and personalized immunotherapy in the future.
| S-EPMC8761291 | biostudies-literature
Project description:Protein tyrosine phosphatase, non-receptor type 11 (PTPN11) is a multifunctional tyrosine phosphatase and has a significant part in many types of tumors. As of yet, neither the expression profile of PTPN11 nor its significance in pan-cancer diagnosis has been clarified. With the assistance of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we have comprehensively mapped the expression profiles, prognostic significance, genetic alteration, phosphorylation status, infiltration of immune cells, and functional properties of PTPN11 in 33 human tumors. There was an inconsistent expression of PTPN11 in different tumors, and the alteration of PTPN11 expression predicted the survival outcomes of cancer patients. A significant association was found between the genetic alteration levels of PTPN11 and some tumor predictions. Besides, the reduced PTPN11 phosphorylation levels were observed in breast cancer, clear cell RCC, head and neck carcinoma, and lung adenocarcinoma (LUAD). Furthermore, there was a significant association between PTPN11 expression and infiltration of cancer-associated fibroblasts and endothelial cells, along with tumor mutation burden, microsatellite instability, mismatch repair genes, and immunoregulators. Finally, pathway enrichment analysis demonstrated that PTPN11-associated terms and pathways were involved in malignancy. Taken together, PTPN11 may become a new biomarker and target for cancer therapy.
| S-EPMC9320542 | biostudies-literature
Project description:BackgroundZinc Finger Protein 337 (ZNF337) is a novel Zinc Finger (ZNF) protein family member. However, the roles of ZNF337 in human cancers have not yet been investigated.MethodsIn this study, with the aid of TCGA databases, GTEx databases, and online websites, we determined the expression levels of ZNF337 in pan-cancer and its potential value as a diagnostic and prognostic marker for pan-cancer and analyzed the relationship between ZNF337 expression and immune cell infiltration and immune checkpoint genes. We then focused our research on the potential of ZNF337 as a biomarker for diagnostic and prognostic in KIRC (kidney renal clear cell carcinoma) and validated in the E-MTAB-1980 database. Moreover, the expression of ZNF337 was detected through qRT-PCR and Western blotting (WB). CCK-8 experiment, colony formation experiment, and EDU experiment were performed to evaluate cell proliferation ability. Wound healing assay and transwell assay were used to analyze its migration ability. The qRT-PCR and WB were used to detect the expression of ZNF337 in tumor tissues and paracancerous tissues of KIRC patients.ResultsThe pan-cancer analysis revealed that abnormal ZNF337 expression was found in multiple human cancer types. ZNF337 had a high diagnostic value in pan-cancer and a significant association with the prognosis of certain cancers, indicating that ZNF337 may be a valuable prognostic biomarker for multiple cancers. Further analysis demonstrated that the expression level of ZNF337 displayed significant correlations with cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes in many tumors. Additionally, ZNF337 was observed to have a high expression in KIRC. Its expression was significantly associated with poor prognosis [overall survival (OS), disease-specific survival (DSS)], age, TNM stage, histologic grade, and pathologic stage. The high ZNF337 expression was associated with poor prognosis in the E-MTAB-1980 validation cohort. The in vitro experiments suggested that the expression of ZNF337 in KIRC tumor tissues was higher than in adjacent tissues, and ZNF337 knockdown inhibited the proliferation and migration of KIRC cells, whereas overexpression of ZNF337 had the opposite effects.ConclusionsZNF337 might be an important prognostic and immunotherapeutic biomarker for pan-cancer, especially in KIRC.
| S-EPMC11313096 | biostudies-literature
Project description:Recent studies have shown that PPP1R14B was highly expressed in tumor tissues and patients with high expression of PPP1R14B had poor survival rates. However, the function and mechanisms of PPP1R14B in tumor progression remain ill defined. There was also lack of pan-cancer evidence for the relationship between PPP1R14B and various tumor types based on abundant clinical data. We used the TCGA project and GEO databases to perform pan-cancer analysis of PPP1R14B, including expression differences, correlations between expression levels and survival, genetic alteration, immune infiltration, and relevant cellular pathways, to investigate the functions and potential mechanisms of PPP1R14B in the pathogenesis or clinical prognosis of different cancers. Herein, we found that PPP1R14B was involved in the prognosis of pan-cancer and closely related to immune infiltration. Increased PPP1R14B expression correlated with poor prognosis and increased immune infiltration levels in myeloid-derived suppressor cells (MDSCs). Our studies suggest that PPP1R14B can be used as a prognostic biomarker for pan-cancer. Our findings may provide an antitumor strategy targeting PPP1R14B, including manipulation of tumor cell growth or the tumor microenvironment, especially myeloid-derived suppressor cell infiltration.
| S-EPMC8631915 | biostudies-literature
Project description:Lung cancer is one of the most common types of cancer worldwide, with the highest incidence and mortality rates. Protein phosphatase, Mg2+/Mn2+ dependent 1G (PPM1G) is a serine/threonine phosphatase, which is involved in the proliferation, invasion and metastasis of tumor cells. However, there are few reports on the role of PPM1G in lung adenocarcinoma (LUAD). The present study used publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases to evaluate the expression of PPM1G in LUAD, and to assess the relationship between PPM1G expression and the prognosis of patients with LUAD. Protein expression data of PPM1G obtained by immunohistochemical staining were collected from the Human Protein Atlas database. The correlation between PPM1G and immune cell infiltration and immune checkpoints was analyzed by single‑sample gene set enrichment analysis of TCGA data. The Kaplan‑Meier method was used for survival analysis, and univariate and multivariate Cox regression were used to analyze the effect of PPM1G on prognosis with data from TCGA database. The results showed that PPM1G was highly expressed in LUAD cancer tissues. The high expression of PPM1G was associated with poor clinical stage, T stage, N stage and overall survival in LUAD. The present study screened 29 genes related to PPM1G and closely related to the cell cycle in patients with LUAD. The expression of PPM1G was positively correlated with γδ‑Τ cells, T helper 2 cells and natural killer CD56dim cells, and was negatively correlated with B cells, mast cells, plasmacytoid dendritic cells, T helper cells, macrophages, T cells, CD8 T cells, central memory T cells, effector memory T cells, neutrophils and T follicular helper cells. In addition, PPM1G was positively correlated with immune detection points. In conclusion, PPM1G may be involved in the control of the lung cancer cell cycle, and could be associated with prognosis and immune infiltration in patients with LUAD.
| S-EPMC10345622 | biostudies-literature
Project description:Paxillin (PXN) is a protein involved in numerous physiological processes, and its presence is closely related to the occurrence and development of many types of tumors. However, no studies have analyzed PXN from a pan-cancer perspective. We analyzed PXN expression, immune cell infiltration, prognosis, and biological function across different types of tumors included in The Cancer Genome Atlas and Gene Expression Omnibus datasets. The results showed that expression of PXN varies in different tumors. Expression of PXN strongly correlated with prognosis in patients with tumors; higher PXN expression usually was linked to poor overall and disease-free survival. Expression of PXN in breast invasive carcinoma and lymphoid neoplasm diffuse large B-cell lymphoma was related to the degree of CD8+ T-cell infiltration, and infiltration of cancer-associated fibroblasts, such as kidney renal papillary cell carcinoma and brain lower-grade glioma, was also observed in other tumors. The results of pan-cancer analysis showed that abnormal PXN expression was related to poor prognosis, immune infiltration, and protein phosphorylation in different tumor types. Therefore, the PXN gene may become a potential biomarker of clinical tumor prognosis.
| S-EPMC8266322 | biostudies-literature
Project description:BackgroundUbiquitin-conjugating enzyme E2 T (UBE2T) is a potential oncogene. However, Pan-cancer analyses of the functional, prognostic and predictive implications of this gene are lacking.MethodsWe first analyzed UBE2T across 33 tumor types in The Cancer Genome Atlas (TCGA) project. We investigated the expression level of UBE2T and its effect on prognosis using the TCGA database. The correlation between UBE2T and cell cycle in pan-cancer was investigated using the single-cell sequencing data in Cancer Single-cell State Atlas (CancerSEA) database. The Weighted Gene Co-expression Network analysis (WGCNA), Univariate Cox and Least absolute shrinkage and selection operator (LASSO) Cox regression models, and receiver operating characteristic (ROC) were applied to assess the prognostic impact of UBE2T-related cell cycle genes (UrCCGs). Furthermore, the consensus clustering (CC) method was adopted to divide TCGA-lung adenocarcinoma (LUAD) patients into subgroups based on UrCCGs. Prognosis, molecular characteristics, and the immune panorama of subgroups were analyzed using Single-sample Gene Set Enrichment Analysis (ssGSEA). Results derived from TCGA-LUAD patients were validated in International Cancer Genome Consortium (ICGC)-LUAD data.ResultsUBE2T is highly expressed and is a prognostic risk factor in most tumors. CancerSEA database analysis revealed that UBE2T was positively associated with the cell cycle in various cancers(r > 0.60, p < 0.001). The risk signature of UrCCGs can reliably predict the prognosis of LUAD (AUC1 year = 0.720, AUC3 year = 0.700, AUC5 year = 0.630). The CC method classified the TCGA-LUAD cohort into 4 UrCCG subtypes (G1-G4). Kaplan-Meier survival analysis demonstrated that G2 and G4 subtypes had worse survival than G3 (Log-rank test PTCGA training set < 0.001, PICGC validation set < 0.001). A comprehensive analysis of immune infiltrates, immune checkpoints, and immunogenic cell death modulators unveiled different immune landscapes for the four subtypes. High immunophenoscore in G3 and G4 tumors suggested that these two subtypes were immunologically "hot," tending to respond to immunotherapy compared to G2 subtypes (p < 0.001).ConclusionsUBE2T is a critical oncogene in many cancers. Moreover, UrCCG classified the LUAD cohort into four subgroups with significantly different survival, molecular features, immune infiltrates, and immunotherapy responses. UBE2T may be a therapeutic target and predictor of prognosis and immunotherapy sensitivity.
| S-EPMC9650835 | biostudies-literature