Neutrophil extracellular trap related risk score exhibits crucial prognostic value in skin cutaneous melanoma, associating with distinct immune characteristics
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ABSTRACT:
SUBMITTER: Zhang H
PROVIDER: S-EPMC11337913 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
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Project description:Skin cutaneous melanoma (SKCM) is a common cancer of which mortality is increasing continuously. Our study conducted a series of analyses on the clinical significance of Serine/threonine kinase 17B (STK17B) in SKCM to provide a new biomarker for diagnosis and treatment. The RNA-sequence data were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. The data of 468 SKCM patients were divided into STK17B high- and low-expression groups and analyzed by Bioconductor package to identify the differential expressed genes. The R package of "clusterProfiler" was used for Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene-Set Enrichment Analysis analyses. A protein-protein interaction network and immune infiltration landscape were respectively constructed via STRING database and ssGSEA. STK17B had lower expression in SKCM than normal tissues. Besides, STK17B expression was significantly related to some clinicopathological characteristics in SKCM patients including T stage, Breslow depth, radiation therapy, melanoma Clark level, and pathologic stage. The Kaplan-Meier curve analyses revealed that the low expression of STK17B was correlated with poor overall survival and disease-specific survival. We constructed nomograms to predict the 1-, 3-, and 5-year survival of SKCM patients. The function enrichment analyses showed STK17B-related differential expressed genes were enriched in cellular differentiation and immune-related progress. STK17B expression level were positively correlated with infiltrating level of immune cells. In this study, we found that STK17B, which played an important role in immune infiltration, could be a new biomarker for diagnosis and prognosis in SKCM patients.
| S-EPMC8849620 | biostudies-literature
Project description:Studies have indicated that Vascular mimicry (VM) could contribute to the unfavorable prognosis of skin cutaneous melanoma (SKCM). Thus, the objective of this study was to identify therapeutic targets associated with VM in SKCM and develop a novel prognostic model. Gene expression data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were utilized to identify differentially expressed genes (DEGs). By intersecting these DEGs with VM genes, we acquired VM-related DEGs specific to SKCM, and then identified prognostic-related VM genes. A VM risk score system was established based on these prognosis-associated VM genes, and patients were then categorized into high- and low-score groups using the median score. Subsequently, differences in clinical characteristics, gene set enrichment analysis (GSEA), and other analyses were further presented between the 2 groups of patients. Finally, a novel prognostic model for SKCM was established using the VM score and clinical characteristics. 26 VM-related DEGs were identified in SKCM, among the identified DEGs associated with VM in SKCM, 5 genes were found to be prognostic-related. The VM risk score system, comprised of these genes, is an independent prognostic risk factor. There were significant differences between the 2 patient groups in terms of age, pathological stage, and T stage. VM risk scores are associated with epithelial biological processes, angiogenesis, regulation of the SKCM immune microenvironment, and sensitivity to targeted drugs. The novel prognostic model demonstrates excellent predictive ability. Our study identified VM-related prognostic markers and therapeutic targets for SKCM, providing novel insights for clinical diagnosis and treatment.
| S-EPMC10869071 | biostudies-literature
Project description:Background: The functional significance of the proteasome activator subunit (PSME) gene family in the pathogenesis of skin cutaneous melanoma (SKCM) remains to be elucidated. Materials and methods: Clinical data for patients with SKCM, including expression levels of PSME genes, were extracted from TCGA. GO term and KEGG pathway enrichment analyses were performed. Correlations between the expression levels of PSME genes in SKCM were evaluated with the Pearson correlation coefficient. Functional and enrichment analyses were conducted using DAVID. Univariate and multivariate survival analyses adjusted by Cox regression were used to construct a prognostic signature. The mechanisms underlying the association between PSME gene expression and overall survival (OS) were explored with gene set enrichment analysis. Joint-effects survival analysis was performed to evaluate the clinical value of the prognostic signature. Results: The median expression levels of PSME1, PSME2 and PSME3 were significantly higher in SKCM than in normal skin. PSME1, PSME2, and PSME3 were significantly enriched in several biological processes and pathways including cell adhesion, adherens junction organization, regulation of autophagy, cellular protein localization, the cell cycle, apoptosis, and the Wnt and NF-κB pathways. High expression levels of PSME1 and PSME2 combined with a low expression level of PSME3 was associated with favorable OS. Conclusion: Knowledge of the expression levels of the PSME gene family could provide a sensitive strategy for predicting prognosis in SKCM.
| S-EPMC6584401 | biostudies-literature
Project description:Background: Skin cutaneous melanoma (SKCM) is a common malignancy that is associated with increased morbidity and mortality. Complement C1Q is composed of C1QA, C1QB, and C1QC and is involved in the occurrence and development of many malignant tumours. However, the effect of C1QA, C1QB, and C1QC expression on tumour immunity and prognosis of cutaneous melanoma remains unclear. Methods: First, we analysed C1QA, C1QB, and C1QC expression levels and prognostic values using Gene Expression Profiling Interactive Analysis (GEPIA) and Tumour Immune Estimation Resource (TIMER) analysis, and further validation was performed using RT-qPCR, The Human Protein Atlas, The Cancer Genome Atlas (TCGA) dataset, and Gene Expression Omnibus dataset. We then performed univariate/multivariate Cox proportional hazard model, clinicopathological correlation, and receiver operating characteristic curve analysis using TCGA dataset and established a nomogram model. Differentially expressed genes associated with C1QA, C1QB, and C1QC in SKCM were identified and analysed using LinkedOmics, TIMER, the Search Tool for the Retrieval of Interacting Genes database, and Metascape and Cytoscape software platforms. We used TIMER, GEPIA, and single-sample gene set enrichment analysis (ssGSEA) to analyse the relationship between the three genes and the level of immune cell infiltration, biomarkers, and checkpoint expression in SKCM. Finally, GSEA was utilized to study the functional pathways of C1QA, C1QB, and C1QC enrichment in SKCM. Results: The overexpression of C1QA, C1QB, and C1QC provided significant value in the diagnosis of SKCM and has been associated with better overall survival (OS). Multivariate Cox regression analysis indicated that C1QA, C1QB, and C1QC are independent prognostic biomarkers for patients with SKCM. Immune cell infiltration, biomarkers, and checkpoints were positively correlated with the expression of C1QA, C1QB, and C1QC. Furthermore, the results of functional and pathway enrichment analysis showed that immune-related and apoptotic pathways were significantly enriched in the high-expression group of C1QA, C1QB, and C1QC. Conclusion: We found that C1QA, C1QB, and C1QC can be used as biomarkers for the diagnosis and prognosis of SKCM patients. The upregulated expression levels of these three complement components benefit patients from OS and may increase the effect of immunotherapy. This result may be due to the dual effects of anti-tumour immunity and apoptosis.
| S-EPMC9468976 | biostudies-literature
Project description:BackgroundSkin cutaneous melanoma (SKCM) is a highly lethal cancer, ranking among the top four deadliest cancers. This underscores the urgent need for novel biomarkers for SKCM diagnosis and prognosis. Anoikis plays a vital role in cancer growth and metastasis, and this study aims to investigate its prognostic value and mechanism of action in SKCM.MethodsUtilizing consensus clustering, the SKCM samples were categorized into two distinct clusters A and B based on anoikis-related genes (ANRGs), with the B group exhibiting lower disease-specific survival (DSS). Gene set enrichment between distinct clusters was examined using Gene Set Variation Analysis (GSVA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.ResultsWe created a predictive model based on three anoikis-related differently expressed genes (DEGs), specifically, FASLG, IGF1, and PIK3R2. Moreover, the mechanism of these prognostic genes within the model was investigated at the cellular level using the single-cell sequencing dataset GSE115978. This analysis revealed that the FASLG gene was highly expressed on cluster 1 of Exhausted CD8( +) T (Tex) cells.ConclusionsIn conclusion, we have established a novel classification system for SKCM based on anoikis, which carries substantial clinical implications for SKCM patients. Notably, the elevated expression of the FASLG gene on cluster 1 of Tex cells could significantly impact SKCM prognosis through anoikis, thus offering a promising target for the development of immunotherapy for SKCM.
| S-EPMC10924820 | biostudies-literature
Project description:B and T lymphocyte attenuator (BTLA) is a newly identified immune checkpoint molecular belonging to the CD28 immunoglobulin superfamily. However, the expression and clinical value of BTLA in skin cutaneous melanoma (SKCM) has not been widely characterized. We found that BTLA levels were upregulated in metastatic melanoma compared to normal skin tissues and primary melanoma. Higher BTLA was also correlated with improved prognosis in SKCM based on several datasets. The multivariate Cox regression model revealed that BTLA was an independent survival indicator in metastatic melanoma. Tumor microenvironment analysis indicated BTLA was positively associated with the infiltrating levels of different immune cells and the activity of the anti-cancer immunity cycle. Importantly, BTLA accurately predicted the outcome of melanoma patients treated with MAGE-A3 blocker or first-line anti-PD-1. The present findings disclose that BTLA is a reliable biomarker for prognosis and immunotherapeutic response and might contribute to developing novel SKCM immunological treatment strategies.
| S-EPMC7953043 | biostudies-literature
Project description:BackgroundMeasures of the adaptive immune response have prognostic and predictive associations in melanoma and other cancer types. Specifically, intratumoral T cell density and function have considerable prognostic and predictive value in skin cutaneous melanoma (SKCM). Less is known about the significance of tumor-infiltrating B cells in SKCM. Our goal was to understand the prognostic and predictive value of B cell phenotypic subsets in SKCM using RNA sequencing.MethodsWe used our previously published algorithm, V'DJer, to assemble B cell receptor (BCR) repertoires and estimate diversity from short-read RNA sequencing (RNA-seq). We applied machine learning-based cellular phenotype classifiers to measure relative similarity of bulk tumor sample gene expression profiles and different B cell phenotypes. We assessed these aspects of B cell biology in 473 SKCM from the Cancer Genome Atlas Project (TCGA) as well as in RNA-seq data corresponding to tumor samples procured from patients who received CTLA-4 and PD-1 inhibitors for metastatic SKCM.ResultsWe found that the BCR repertoire was associated with different clinical factors, such as tumor tissue site and sex. However, increased clonality of the BCR repertoire was favorably prognostic in SKCM and was prognostic even after first conditioning on various clinical factors. Mutation burden was not correlated with any BCR measurement, and no specific mutation had an altered BCR repertoire. Lack of an assembled BCR in pre-treatment tumor tissues was associated with a lack of anti-tumor response to a CTLA-4 inhibitor in metastatic SKCM.ConclusionsThese findings suggest an important prognostic and predictive role for B cell characteristics in SKCM. This has implications for melanoma immunobiology and potential development of immunogenomics features to predict survival and response to immunotherapy.
| S-EPMC6540526 | biostudies-literature
Project description:Skin cutaneous melanoma (SKCM) is the most lethal tumor among three of the major malignant cancers of the skin. The mechanism underlying the malignant biological behaviors of SKCM is not fully clear. Our study intended to verify the molecular mechanism of proteasome 26 S subunit ATPase 2 (PSMC2) in malignant biological behaviors of SKCM. The Cancer Genome Atlas (TCGA) database was used to analyze the expression of PSMC2 in SKCM and its impact on prognosis. PSMC2 expression in 105 paired SKCM tissues was investigated by immunohistochemistry (IHC), its functional roles were verified using a series of cell experiments, and the underlying pathway was detected by protein-chip technology and gene set enrichment analysis. We found that PSMC2 was significantly upregulated in SKCN patients from TCGA datasets and verified in clinical SKCM tissues. Moreover, high PSMC2 was shown to closely correlate with the pathological stages and lymphatic metastasis of SKCM patients. Functionally, knockdown of PSMC2 suppressed the progression of SKCM through inhibiting cell proliferation, migration, and DNA damage in vitro as well as cell growth in vivo, whereas inducing apoptosis, cycle arrest in G2 phase. Similarly, pharmaceutical inhibition of proteasome with MG132 mimicked the PSMC2 knockdown induced defects in cell cycle arrest, apoptosis and proliferation, while overexpression of PSMC2 has the opposite effects. Mechanistically, the silence of PSMC2 remarkably elevated the pro-apoptotic proteins DR6, IGFBP-4, p21, and p53, while inhibited the anti-apoptosis protein TRAILR-3 and the proteins related to the Wnt signaling pathway. The present study revealed that PSMC2 participated in a positive regulation to promote the progression of SKCM through regulating the Wnt signaling pathway. Our findings may offer a new mechanism underlying the development and progression of SKCM, and a deeper understanding of PSMC2 may contribute to SKCM treatment.
| S-EPMC8556233 | biostudies-literature
Project description:Background: Skin cutaneous melanoma (SKCM) is one of the most common cutaneous malignancies, which incidence is increasing. Cuproptosis is a new type of programming cell death recently reported, which may affect the progression of SKCM. Method: The mRNA expression data of melanoma were obtained from the Gene Expression Omnibus and the Cancer Genome Atlas databases. We constructed a prognostic model according to the cuproptosis-related differential genes in SKCM. Finally, real-time quantitative PCR was performed to verify the expression of cuproptosis-related differential genes in patients with different stages of cutaneous melanoma. Results: We detected 767 cuproptosis-related differential genes based on 19 cuproptosis-related genes, and screened out 7 differential genes to construct a prognostic model, which including three high-risk differential genes (SNAI2, RAP1GAP, BCHE), and four low-risk differential genes (JSRP1, HAPLN3, HHEX, ERAP2). Kaplan-Meier analysis indicated that SKCM patients with low-risk differential genes signals had better prognosis. The Encyclopedia of Genomes results manifested that cuproptosis-related differential genes are not only involved in T cell receptor signaling channel, natural killer cell mediated cytotoxicity, but also chemokine signaling pathway and B cell receptor signaling pathway. In our risk scoring model, the receiver operating characteristic (ROC) values of the three-time nodes are 0.669 (1-year), 0.669 (3-year) and 0.685 (5-year), respectively. Moreover, the tumor burden mutational and immunology function, cell stemness characteristics and drug sensitivity have significant differences between low-risk group and high-risk group. The mRNA level of SNAI2, RAP1GAP and BCHE in stage Ⅲ+Ⅳ SKCM patients was significantly higher than that in stage Ⅰ+Ⅱ patients, while the level of JSRP1, HAPLN3, HHEX and ERAP2 in stage Ⅰ+Ⅱ SKCM patients was more remarkable higher than that in stage Ⅲ+Ⅳ SKCM patients. Conclusion: In summary, we suggest that cuproptosis can not only regulate the tumor immune microenvironment but also affect the prognosis of SKCM patients, and may offer a basic theory for SKCM patients survival studies and clinical decision-making with potentially therapeutic drugs.
| S-EPMC10149708 | biostudies-literature
Project description:Tissue Transglutaminases (TGs) are crosslinking enzymes with pleiotropic functions that have been linked to the development and progression of numerous cancers, with a recent focus on their ability to remodel the tumor microenvironment. Although several pieces of evidence demonstrated their importance in the regulation of the major signaling pathways that control oncogenesis, the correlation between TGs with clinical and pathological features remains controversial and to be further explored. Moreover, an assessment of the TGs alterations together with a functional analysis associated with clinical features and prognostic values are still lacking and would help to understand these intricacies, particularly in human cancers. In the present study, we processed data from numerous public datasets to investigate TGs distribution and prognostic signature in cancer patients. Here, we found that skin cutaneous melanoma (SKCM) shows the highest abundance of TGs mutations among the other human cancers. Interestingly, among all the TGs, TG2 is the only member whose expression is associated with a better overall survival in SKCM, although its expression increases with the worsening of the tumor phenotype. Our analysis revealed a strong positive association between TG2 expression and anti-tumoral immune response, which would explain the relationship between high mRNA levels and better overall survival. Our data suggest that TG2 may be presented as a new promising immune biomarker of prognosis in SKCM, which may contribute to identifying patients who would benefit the most from adjuvant immunotherapy.
| S-EPMC9209462 | biostudies-literature