A Pan-Cancer Analysis of Clinical Prognosis and Immune Infiltration of CKS1B in Human Tumors.
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ABSTRACT:
SUBMITTER: Jia Y
PROVIDER: S-EPMC8627364 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundImmunotherapy has significantly improved patient outcomes, but encountered obstacles recently. CD96, a novel immune checkpoint expressed on T cells and natural killer (NK) cells, is essential for regulating immune functions. However, how CD96 correlating with immune infiltration and patient prognosis in pan-cancer remains unclear.MethodsHPA, TCGA, GEO, GTEx, Oncomine, TIMER2.0, PrognoScan, Linkedomics, Metascape, and GEPIA2 databases were used to analyze CD96 in cancers. Visualization of data was mostly achieved by R language, version 4.0.2.ResultsIn general, CD96 was differentially expressed between most cancer and adjacent normal tissues. CD96 significantly impacted the prognosis of diverse cancers. Especially, high CD96 expression was associated with poorer overall survival (OS) and disease-specific survival (DSS) in the TCGA lower grade glioma (LGG) cohort (OS, HR = 2.18, 95% CI = 1.79-2.66, P < 0.001). The opposite association was significantly observed in skin cutaneous melanoma (SKCM) cohort (OS, HR = 0.96, 95% CI = 0.94-0.98, P < 0.001). Notably, SKCM samples demonstrated the highest CD96 mutation frequency among all cancer types. Furthermore, in most cancers, CD96 expression level was significantly correlated with expression levels of recognized immune checkpoints and abundance of multiple immune infiltrates including CD8+ T cells, dendric cells (DCs), macrophages, monocytes, NK cells, neutrophils, regulatory T cells (Tregs), and follicular helper T cells (Tfh). CD96 was identified as a risk factor, protective factor, and irrelevant variable in LGG, SKCM and adrenocortical carcinoma (ACC), respectively. CD96 related genes were involved in negative regulation of leukocyte in LGG, however, involved in multiple positive immune processes in SKCM. Furthermore, CD96 was significantly associated with particular immune marker subsets. Importantly, it strongly correlated with markers of type 1 helper T cell (Th1) in SKCM, but not in LGG or ACC either.ConclusionsCD96 participates in diverse immune responses, governs immune cell infiltration, and impacts malignant properties of various cancer types, thus standing as a potential biomarker for determining patient prognosis and immune infiltration in multiple cancers, especially in glioma and melanoma.
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Project description:Background: The function of olfactomedin-like 2B (OLFML2B), as a member of the olfactomedin domain-containing protein family, remains ambiguous, especially in tumors. The current study explores the possible correlation between OLFML2B, prognosis, and immune infiltration in pan-cancer. Methods: We applied a number of bioinformatics techniques to probe the prospective function of OLFML2B, consisting of its association with prognosis, clinicopathology, alteration, GSEA, tumor microenvironment (TME), immune-associated genes, immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and drug sensitivity in several cancer types. qPCR and immunohistochemistry were used to identify OLFML2B expression in LIHC cell lines and liver cancer tissues. Results: We discovered that OLFML2B was overexpressed in 14 cancers and positively related to several cancer type prognoses. The expression of OLFML2B was further validated in the LIHC cell lines. OLFML2B expression was bound up with TMB in 13 cancers, MSI in 10 cancers, and TME in almost all cancers. Furthermore, OLFML2B was highly co-expressed with genes encoding immune activators and immune suppressors. We further found that OLFML2B played a role in infiltrating different types of immune cells, such as macrophages and cancer-associated fibroblasts. OLFML2B may influence various cancer and immune-related pathways, such as the PI3K-Akt signaling pathway, ECM-receptor interaction, focal adhesion, and leukocyte transendothelial migration. In addition, OLFML2B may increase drug resistance of binimetinib, cobimentinib, and trametinib. Conclusion: Our outcomes reveal that OLFML2B may act as a prognostic marker and a potential target in immunotherapy for diverse tumors due to its oncogenesis function and immune infiltration.
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Project description:Long non-coding RNA known as ASB16 antisense RNA1 (ASB16-AS1) has been proven to be an oncogene, and the relationship between ASB16-AS1 and immunity is still under studied. This study aims to explore the expression and prognostic potential of ASB16-AS1, and to visualize the relationship between ASB16-AS1 expression and immune infiltration in pan-cancer analysis. We clarified ASB16-AS1 expression patterns and its relationship with prognosis through multi-platform and multi-database sources. We also verified the function of ASB16-AS1 in liver hepatocellular carcinoma (LIHC). A variety of immune cell content evaluation methods were used to mutually verify the correlation between ASB16-AS1 and immune infiltration. Finally, the relationships between ASB16-AS1 and molecular characteristics were further explored. In terms of comprehensive analysis, compared with non-tumor tissues, ASB16-AS1 was highly expressed in tumor tissues, and indicated the value of poor prognosis in multiple cancer types. Functional assays, such as counting kit-8 assay, transwell assay and scratch-wound assay verified that high ASB16-AS1 expression promoted tumor progression in LIHC. ASB16-AS1 was positively correlated with B cells, T cells CD4+ and T cells CD8+ in most cancer types, and negatively correlated with macrophages, dendritic cells and neutrophils in some cancer types. In addition, there were different interaction modes between ASB16-AS1 and molecular features, such as the relationship with oncogenic signaling pathways, showing that the high ASB16-AS1 expression was related to alterations in oncogenic signaling pathways. Our study emphasizes that ASB16-AS1 is a potential pan-cancer prognostic marker, whichs is associated with the immune infiltration in multiple cancer types.
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Project description:Response to radiotherapy (RT) in cancers varies widely among patients. Therefore, it is very important to predict who will benefit from RT before clinical treatment. Consideration of the immune tumor microenvironment (TME) could provide novel insight into tumor treatment options. In this study, we investigated the link between immune infiltration status and clinical RT outcome in order to identify certain leukocyte subsets that could potentially influence the clinical RT benefit across cancers. By integrally analyzing the TCGA data across seven cancers, we identified complex associations between immune infiltration and patients RT outcomes. Besides, immune cells showed large differences in their populations in various cancers, and the most abundant cells were resting memory CD4 T cells. Additionally, the proportion of activated CD4 memory T cells and activated mast cells, albeit at low number, were closely related to RT overall survival in multiple cancers. Furthermore, a prognostic model for RT outcomes was established with good performance based on the immune infiltration status. Summarized, immune infiltration was found to be of significant clinical relevance to RT outcomes. These findings may help to shed light on the impact of tumor-associated immune cell infiltration on cancer RT outcomes, and identify biomarkers and therapeutic targets.
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Project description:BackgroundMatrix metalloproteinase 14 (MMP14) is a member of the MMP family, which interacts with tissue inhibitors of metalloproteinase (TIMPs), and is involved in normal physiological functions such as cell migration, invasion, metastasis, angiogenesis, and proliferation, as well as tumor genesis and progression. However, there has been a lack of relevant reports on the effect of MMP14 across cancers. This study aims to explore the correlation between MMP14 and pan-cancer prognosis, immune infiltration, and the effects of pan-cancer gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB), DNA methylation, and immune checkpoint genes.MethodsIn this study, we used bioinformatics to analyze data from multiple databases, including The Cancer Genome Atlas (TCGA), ONCOMINE, and Kaplan-Meier plotter. We investigated the relationship between the expression of MMP14 in tumors and tumor prognosis, the relationship between MMP14 expression and tumor cell immune infiltration, and the relationship between MMR gene MMR, MSI, TMB, DNA methylation, and immune checkpoint genes.ResultsMMP14 expression is highly associated with the prognosis of a variety of cancers and tumor immune invasion and has important effects on pan oncologic MMR, MSI, TMB, DNA methylation, and immune checkpoint genes.ConclusionMMP14 is highly correlated with tumor prognosis and immune invasion and affects the occurrence and progression of many tumors. All of these results fully indicate that MMP14 may be a biomarker for the prognosis, diagnosis, and treatment of many tumors and provide new ideas and direction for subsequent tumor immune research and treatment strategies.
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Project description:Background: Deoxythymidylate kinase (DTYMK) serves as a pyrimidine metabolic rate-limiting enzyme that catalyzes deoxythymidine monophosphate (dTMP) to generate deoxythymidine diphosphate (dTDP). It remains unclear whether DTYMK expression has the potential to predict outcome and immune cell infiltration in cancers. Methods: DTYMK expression profile was analyzed using Oncomine, TIMER, GEPIA and UALCAN databases. The influence of DTYMK on immune infiltration was examined using TIMER and TISIDB databases. DTYMK interactive gene hub and co-expressing genes were obtained and analyzed by STRING and Linkedomics, respectively. The relationship between DTYMK expression and patient prognosis was validated using GEPIA, Kaplan-Meier plotter, and PrognoScan databases. The functions of DTYMK in cancer cells were also biologically validated in vitro. Results: DTYMK expression was elevated in tumor tissues compared with their control counterparts. DTYMK expression varied in different stages and discriminatorily distributed in different immune and molecular subtypes. Higher expression of DTYMK predicted worse outcome in several cancer types such as liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD). High DTYMK expression was positively or negatively correlated with immune cell infiltration, including B cell, CD8+ cell, CD4+ T cell, macrophage, neutrophil and dendritic cell, depending on the type of cancers. Additionally, DTYMK co-expressing genes participated in pyrimidine metabolism as well as in T helper cell differentiation in LIHC and LUAD. In vitro, knockdown of DTYMK suppressed cell migration of liver and lung cancer cells. Conclusion: DTYMK might be taken as an useful prognostic and immunological marker in cancers and further investigation is warrented.
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Project description:BackgroundAs a crucial constituent part of Polycomb repressive complex 2, PHD finger protein 19 (PHF19) plays a pivotal role in epigenetic regulation, and acts as a critical regulator of multiple pathophysiological processes. However, the exact roles of PHF19 in cancers remain enigmatic. The present research was primarily designed to provide the prognostic landscape visualizations of PHF19 in cancers, and study the correlations between PHF19 expression and immune infiltration characteristics in tumor microenvironment.MethodsRaw data in regard to PHF19 expression were extracted from TCGA and GEO data portals. We examined the expression patterns, prognostic values, mutation landscapes, and protein-protein interaction network of PHF19 in pan-cancer utilizing multiple databases, and investigated the relationship of PHF19 expression with immune infiltrates across TCGA-sequenced cancers. The R language was used to conduct KEGG and GO enrichment analyses. Besides, we built a risk-score model of hepatocellular carcinoma (HCC) and validated its prognostic classification efficiency.ResultsOn balance, PHF19 expression was significantly higher in cancers in comparison with that in noncancerous samples. Increased expression of PHF19 was detrimental to the clinical prognoses of cancer patients, especially HCC. There were significant correlations between PHF19 expression and TMB or MSI in several cancers. High PHF19 levels were critically associated with the infiltration of myeloid-derived suppressor cells (MDSCs) and Th2 subsets of CD4+ T cells in most cancers. Enrichment analyses revealed that PHF19 participated in regulating carcinogenic processes including cell cycle and DNA replication, and was correlated with the progression of HCC. Intriguingly, GSEA suggested that PHF19 was correlated with the cellular components including immunoglobulin complex and T cell receptor complex in HCC. Based on PHF19-associated functional gene sets, an eleven-gene prognostic signature was constructed to predict HCC prognosis. Finally, we validated pan-cancer PHF19 expression, and its impacts on immune infiltrates in HCC.ConclusionThe epigenetic related regulator PHF19 participates in the carcinogenic progression of multiple cancers, and may contribute to the immune infiltration in tumor microenvironment. Our study suggests that PHF19 can serve as a carcinogenic indicator related to prognosis in pan-cancer, especially HCC, and shed new light on therapeutics of cancers for clinicians.
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Project description:Background C-X-C chemokine receptor 4 (CXCR4) is a specific receptor of stromal cell-derived factor-1, also known as CXCL12. The interaction between CXCL12 and its receptor CXCR4 can activate various signaling pathways, including gene expression, cell proliferation, migration, tumorigenesis, angiogenesis, etc. Although there is evidence to support the association between CXCR4 and some cancers, there is no pan-cancer analysis. To fill this gap, we analyzed the role of CXCR4 in cancer-based on The Cancer Genome Atlas (TCGA). Methods We used TCGA, Genotype-Tissue Expression (GTEx) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases to analyze the expression, variation and phosphorylation of CXCR4 in different cancers. At the same time, we also carried out Kyoto Encyclopedia of Genes (KEGG) and Gene Ontology (GO) enrichment analysis. Results We found that CXCR4 expression was significantly increased in bladder urothelial carcinoma (BLCA) and other cancers, and CXCR4 expression in BLCA, cervical squamous cell carcinoma (CESC) and other cancers was related to tumor stage. CXCR4 expression was positively correlated with tumor-associated fibroblasts in BLCA, breast adenocarcinoma (BRCA), CESC and other cancers. GO analysis showed that CXCR4-related genes were mainly enriched in biological processes (BPs) and cellular components (CCs). KEGG analysis showed that CXCR4 was mainly involved in “chemokine signaling pathway”, “natural killer cell-mediated cytotoxicity”, and “JAK-STAT signaling pathway”. Conclusions The expression of CXCR4 in different cancers has different effects on the prognosis of patients and the infiltration of immune cells.
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Project description:TNFAIP8L1, as a recently identified member in TNFAIP8 family, plays an important role in tumorigenesis. However, a pan-cancer analysis of TNFAIP8L1 in human tumors has not been conducted until now. The main purpose of study is to investigate TNFAIP8L1 during 33 different types of human tumors by using TCGA and GTEx. The pan-cancer analysis showed that TNFAIP8L1 was significantly over-expressed in 15 cancers and low-expressed in 9 cancers. There were distinct relations between TNFAIP8L1 expression and prognosis of patients with cancer. Furthermore, we also found that DNA methylation and RNA modification of TNFAIP8L1 were associated with many cancers. And then, we detected that TNFAIP8L1 level was positively associated with cancer-associated fibroblasts (CAFs) in many tumors. And, we obtained that TNFAIP8L1 expression was related with most of immune inhibitory and stimulatory genes in multiple types of tumors. We also found TNFAIP8L1 expression was correlated with most of chemokine, receptor, MHC, immunoinhibitor and immunostimulator gens in most of cancers. Moreover, we detected TNFAIP8L1 expression was associated with TMB and MSI in several tumors. Finally, TNFAIP8L1 gene had a significant positive association with 5 genes including BCL6B, DLL4, PCDH12, COL4A1 and DLL4 in the majority of tumors. GO enrichment and KEGG pathway analyses showed that TNFAIP8L1 in thepathogenesis of cancer may be related to "purine nucleoside binding," "purine ribonucleoside binding," "ECM-receptor interaction," etc. Our first pan-cancer study may provide a deep comprehending of TNFAIP8L1 in tumoeigenesis from different tumors.
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Project description:Objective: Because of the modest immunotherapeutic response among ovarian carcinoma (OC) patients, it is significant to evaluate antitumor immune response and develop more effective precision immunotherapeutic regimens. Here, this study aimed to determine diverse immune subtypes of OC. Methods: This study curated the expression profiles of prognostic immunologically relevant genes and conducted consensus clustering analyses for determining immune subtypes among OC patients in TCGA cohort. With Boruta algorithm, characteristic genes were screened for conducting an immune scoring system through principal component analysis algorithm. The single-sample gene set enrichment analysis and ESTIAMTE methods were adopted for quantifying the immune infiltrates and responses to chemotherapeutic agents were estimated with pRRophetic algorithm. Two immunotherapeutic cohorts were used for investigating the efficacy of immune score in predicting therapeutic benefits. Results: Two immune subtypes were conducted among 377 OC patients. Immune subtype 2 was characterized by worse clinical prognosis, more frequent genetic variations and mutations, enhanced immune infiltrates, and increased expression of MHC molecules and programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1). In total, 30 prognosis-relevant characteristic immune subtype-derived genes were identified for constructing the immune score of OC patients. High immune score was linked with more dismal prognosis, decreased immune infiltrations, and expression of MHC molecules. High immune score presented favorable sensitivity to doxorubicin and vinorelbine and reduced sensitivity to cisplatin. In addition, immune score possessed the potential in predicting benefits from anti-PD-1/PD-L1 therapy. Conclusion: Collectively, our findings propose two complex and diverse immune subtypes of OC. Quantitative assessment of immune subtypes in individual patients strengthens the understanding of tumor microenvironment features and promotes more effective immunotherapeutic regimens.
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