Tetraspanin8 expression predicts an increased metastatic risk and is associated with cancer-related death in human cutaneous melanoma.
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ABSTRACT:
SUBMITTER: Berthier-Vergnes O
PROVIDER: S-EPMC8487126 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThe objective of this study was to test the hypothesis that p53 Arg72Pro polymorphism may contribute to an increased risk of cutaneous melanoma (CM).MethodsBy searching the databases of PubMed, EMBASE, and Web of Science, a total of 8 eligible case-control studies with 1,957 CM cases and 2,887 controls were included in this meta-analysis. Stata software was used to analyze all the statistical data.ResultsThe pooled data by a fixed-effects model suggested an increased risk of CM associated with p53 Arg72Pro polymorphism under the genetic model of Arg/Pro vs. Pro/Pro without heterogeneity (ORArg/Pro vs. Pro/Pro = 1.76, 95% CI = 1.55-1.99, Pheterogeneity = 0.075). A similar trend was seen in subgroups of hospital-based studies and population-based studies.ConclusionOur meta-analysis based on all studies shows that the p53 Arg72Pro polymorphism may increase individual susceptibility to CM, particularly in Caucasians and could serve as a biomarker to predict the population at high risk of CM.
| S-EPMC4361629 | biostudies-literature
Project description:The prolyl isomerase Pin1 is widely over-expressed or over-activated in cancers and promotes tumorigenesis. The authors investigated the expression level of Pin1 and analyzed the prognostic value of Pin1 expression using a large-scale melanoma tissue microarray study. Two independent sets of tissue microarrays were employed, including 114 melanoma cases in the discovery set and 424 in the validation set (538 cases in total), 32 normal nevi and 86 dysplastic nevi 118 cases of nevi. The subcellular Pin1 expression in different stages of melanocytic lesions and its prognostic significance were studied. High expression (IRS 0-8) of cytoplasmic Pin1 was observed in 3.13%, 8.33%, 16.49% and 22.76% of the biopsies in normal nevi, dysplastic nevi, primary melanoma and metastatic melanoma, respectively. Significant differences for cytoplasmic Pin1 staining were observed between normal nevi and metastatic melanoma (P?=?0.011, ?2 test), between dysplastic nevi and primary melanoma (P?=?0.046, ?2 test) and between dysplastic nevi and metastatic melanoma (P?=?0.016, ?2 test). Kaplan-Meier survival analysis showed that increased cytoplasmic Pin1 expression was associated with a worse 5-year melanoma-specific survival of melanoma (P?<?0.001) and metastatic melanoma patients (P?=?0.004). Multivariate Cox regression analysis showed that cytoplasmic Pin1 expression is an independent prognostic factor in melanoma. Our data indicate that cytoplasmic Pin1 plays an important role in melanoma pathogenesis and progression, and serve as a potential prognostic marker for melanoma.
| S-EPMC6238011 | biostudies-literature
Project description:Background: Ferroptosis is an iron-dependent cell death mode and closely linked to various cancers, including skin cutaneous melanoma (SKCM). Although attempts have been made to construct ferroptosis-related gene (FRG) signatures for predicting the prognosis of SKCM, the prognostic impact of ferroptosis-related genetic mutations in SKCM remains lacking. This study aims to develop a prediction model to explain the relationship between ferroptosis-related genetic mutations and clinical outcomes of SKCM patients and to explore the potential value of ferroptosis in SKCM treatment. Methods: FRGs which significantly correlated with the prognosis of SKCM were firstly screened based on their single-nucleotide variant (SNV) status by univariate Cox regression analysis. Subsequently, the least absolute shrinkage and selection operator (LASSO) and Cox regressions were performed to construct a new ferroptosis-related genetic mutation risk (FerrGR) model for predicting the prognosis of SKCM. We then illustrate the survival and receiver operating characteristic (ROC) curves to evaluate the predictive power of the FerrGR model. Moreover, independent prognostic factors, genomic and clinical characteristics, immunotherapy, immune infiltration, and sensitive drugs were compared between high-and low-FerrGR groups. Results: The FerrGR model was developed with a good performance on survival and ROC analysis. It was a robust independent prognostic indicator and followed a nomogram constructed to predict prognostic outcomes for SKCM patients. Besides, FerrGR combined with tumor mutational burden (TMB) or MSI (microsatellite instability) was considered as a combined biomarker for immunotherapy response. The high FerrGR group patients were associated with an inhibitory immune microenvironment. Furthermore, potential drugs target to high FerrGR samples were predicted. Conclusion: The FerrGR model is valuable to predict prognosis and immunotherapy in SKCM patients. It offers a novel therapeutic option for SKCM.
| S-EPMC9849373 | biostudies-literature
Project description:PurposeFerroptosis-related lncRNAs are promising biomarkers for predicting the prognosis of many cancers. However, a ferroptosis-related signature to predict the prognosis of cutaneous melanoma (CM) has not been identified. The purpose of this study was to construct a ferroptosis-related lncRNA signature to predict prognosis and immunotherapy efficacy in CM.MethodsFerroptosis-related differentially expressed genes (FDEGs) and lncRNAs (FDELs) were identified using TCGA, GTEx, and FerrDb datasets. We performed Cox and LASSO regressions to identify key FDELs, and constructed a risk score to stratify patients into high- and low-risk groups. The lncRNA signature was evaluated using the areas under the receiver operating characteristic curves (AUCs) and Kaplan-Meier analyses in the training, testing, and entire cohorts. Multivariate Cox regression analyses including the lncRNA signature and common clinicopathological characteristics were performed to identify independent predictors of overall survival (OS). A nomogram was developed for clinical use. We performed gene set enrichment analyses (GSEA) to identify significantly enriched pathways. Differences in the tumor microenvironment (TME) between the 2 groups were assessed using 7 algorithms. To predict the efficacy of immune checkpoint inhibitors (ICI), we analyzed the association between PD1 and CTLA4 expression and the risk score. Finally, differences in Tumor Mutational Burden (TMB) and molecular drugs Sensitivity between the 2 groups were performed.ResultsWe identified 5 lncRNAs (AATBC, AC145423.2, LINC01871, AC125807.2, and AC245041.1) to construct the risk score. The AUC of the lncRNA signature was 0.743 in the training cohort and was validated in the testing and entire cohorts. Kaplan-Meier analyses revealed that the high-risk group had poorer prognosis. Multivariate Cox regression showed that the lncRNA signature was an independent predictor of OS with higher accuracy than traditional clinicopathological features. The 1-, 3-, and 5-year survival probabilities for CM patients were 92.7%, 57.2%, and 40.2% with an AUC of 0.804, indicating a good accuracy and reliability of the nomogram. GSEA showed that the high-risk group had lower ferroptosis and immune response. TME analyses confirmed that the high-risk group had lower immune cell infiltration (e.g., CD8+ T cells, CD4+ memory-activated T cells, and M1 macrophages) and lower immune functions (e.g., immune checkpoint activation). Low-risk patients whose disease expressed PD1 or CTLA4 were likely to respond better to ICIs. The analysis demonstrated that the TMB had significantly difference between low- and high- risk groups. Chemotherapy drugs, such as sorafenib, Imatinib, ABT.888 (Veliparib), Docetaxel, and Paclitaxel showed Significant differences in the estimated IC50 between the two risk groups.ConclusionOur novel ferroptosis-related lncRNA signature was able to accurately predict the prognosis and ICI outcomes of CM patients. These ferroptosis-related lncRNAs might be potential biomarkers and therapeutic targets for CM.
| S-EPMC9354448 | biostudies-literature
Project description:BACKGROUND:BAP1 has been shown to be a target of both somatic alteration in high-risk ocular melanomas (OM) and germline inactivation in a few individuals from cancer-prone families. These findings suggest that constitutional BAP1 changes may predispose individuals to metastatic OM and that familial permeation of deleterious alleles could delineate a new cancer syndrome. DESIGN:To characterize BAP1's contribution to melanoma risk, we sequenced BAP1 in a set of 100 patients with OM, including 50 metastatic OM cases and 50 matched non-metastatic OM controls, and 200 individuals with cutaneous melanoma (CM) including 7 CM patients from CM-OM families and 193 CM patients from CM-non-OM kindreds. RESULTS:Germline BAP1 mutations were detected in 4/50 patients with metastatic OM and 0/50 cases of non-metastatic OM (8% vs. 0%, p?=?0.059). Since 2/4 of the BAP1 carriers reported a family history of CM, we analyzed 200 additional hereditary CM patients and found mutations in 2/7 CM probands from CM-OM families and 1/193 probands from CM-non-OM kindreds (29% vs. 0.52%, p?=?.003). Germline mutations co-segregated with both CM and OM phenotypes and were associated with the presence of unique nevoid melanomas and highly atypical nevoid melanoma-like melanocytic proliferations (NEMMPs). Interestingly, 7/14 germline variants identified to date reside in C-terminus suggesting that the BRCA1 binding domain is important in cancer predisposition. CONCLUSION:Germline BAP1 mutations are associated with a more aggressive OM phenotype and a recurrent phenotypic complex of cutaneous/ocular melanoma, atypical melanocytic proliferations and other internal neoplasms (ie. COMMON syndrome), which could be a useful clinical marker for constitutive BAP1 inactivation.
| S-EPMC3335872 | biostudies-literature
Project description:The absence of BRCA1-associated protein 1 (BAP1) expression in uveal melanoma (UM) is associated with metastatic progression and reduced survival. In this study, we examine nuclear BAP1 (nBAP1) protein expression in primary UMs (PUMs) that show both 'typical' and 'atypical' clinical courses according to their chromosome 3 status, and secondary hepatic metastatic UM (MUM), correlating the results with histological, clinical and survival data.Nuclear BAP1 expression was immunohistochemically assessed in tissue microarrays (TMAs) of: (a) 68 PUM patients, who had been treated surgically; and (b) 13 MUM patients, with 5 cases being paired with primary tumour tissue. All cases were fully annotated. The percentage of tumour cell nuclei staining positively for BAP1 was scored by independent observers.Nuclear BAP1 protein expression was absent in 35 out of 68 (51%) PUM patients, correlating strongly with poor prognostic clinicopathological and genetic parameters and reduced survival (Log rank, P<0.001). Lack of nBAP1 expression importantly identified a subset of 'atypical' PUM patients with disomy of chromosome 3 but with unexpected metastatic relapse. Nuclear BAP1 expression was absent in 10 out of 13 (77%) MUM and expression was concordant in all paired PUM and MUM patients.Absent nBAP1 protein expression is an independent survival predictor for UM patients, easily examined using immunohistochemistry.
| S-EPMC4183849 | biostudies-other
Project description:BackgroundCutaneous melanoma is a common but aggressive tumor. Ferroptosis is a recently discovered cell death with important roles in tumor biology. Nevertheless, the prognostic power of ferroptosis-linked genes remained unclear in cutaneous melanoma.MethodsCutaneous melanoma patients of TCGA (The Cancer Genome Atlas) were taken as the training cohort while GSE65904 and GSE22153 as the validation cohorts. Multifactor Cox regression model was used to build a prognostic model, and the performance of the model was assessed. Functional enrichment and immune infiltration analysis were used to clarify the mechanisms.ResultsA five ferroptosis-linked gene predictive model was developed. ALOX5 and GCH1 were illustrated as independent predictive factors. Functional assessment showed enriched immune-linked cascades. Immune infiltrating analysis exhibited the distinct immune microenvironment.ConclusionHerein, a novel ferroptosis-related gene prognostic model was built in cutaneous melanoma. This model could be used for prognostic prediction, and maybe helpful for the targeted and immunotherapies.
| S-EPMC8384470 | biostudies-literature
Project description:Immunotherapies have changed the medical management of metastatic melanoma. However, the early detection of patients who do not respond to these treatments is a key issue. We evaluated the quantitative monitoring of circulating tumor DNA (ctDNA) as an early predictor of response to anti-PD1. Patients treated with anti-PD1 for metastatic mutated melanoma were selected. The somatic alteration detected on the tumor tissue was quantified on plasma DNA by digital PCR (dPCR) at treatment initiation, after 2 and 4 weeks of treatment, and then every 4 weeks until progression. The absence of biological response (defined as a significant decrease in the amount of ctDNA relative to the baseline level) after 2 weeks of treatment was associated with a lack of clinical benefit under anti-PD1. In the presence of a biological response at week 2, detection of subsequent biological progression (significant increase in the amount of ctDNA relative to its nadir) was 100% predictive of progressive disease, on average 75 days prior to radiological detection. Patients with a persistent biological response beyond week 16 did not experience any progressive disease and exhibited sustained responses. In conclusion, we show that quantitative monitoring of ctDNA, using criteria accounting for dPCR measurement imprecision, allows the early and specific detection of patients who do not respond to anti-PD1 therapy.
| S-EPMC5982743 | biostudies-literature
Project description:BackgroundThe outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease recurrence and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma.Patients and methodsctDNA was analysed in blood specimens that were collected pre-operatively from 174 patients with stage III melanoma undergoing complete lymph node (LN) dissection. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for distant metastasis recurrence-free survival and melanoma-specific survival (MSS).ResultsThe detection of ctDNA in the discovery and validation cohort was 34% and 33%, respectively, and was associated with larger nodal melanoma deposit, higher number of melanoma involved LNs, more advanced stage and high lactate dehydrogenase (LDH) levels. Detectable ctDNA was significantly associated with worse MSS in the discovery [hazard ratio (HR) 2.11 P < 0.01] and validation cohort (HR 2.29, P = 0.04) and remained significant in a multivariable analysis (HR 1.85, P = 0.04). ctDNA further sub-stratified patients with AJCC stage III substage, with increasing significance observed in more advanced stage melanoma.ConclusionPre-operative ctDNA predicts MSS in high-risk stage III melanoma patients undergoing complete LN dissection, independent of stage III substage. This biomarker may have an important role in determining prognosis and stratifying patients for adjuvant treatment.
| S-EPMC6551453 | biostudies-literature
Project description: Not available
| S-EPMC7711084 | biostudies-literature