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Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival

ABSTRACT: Although remission rates for metastatic melanoma are generally very poor, some patients can survive for prolonged periods following metastasis. We used gene expression profiling, mitotic index (MI), and quantification of tumor infiltrating leukocytes (TILs) and CD3+ cells in metastatic lesions to search for a molecular basis for this observation and to develop improved methods for predicting patient survival. We identified a group of 266 genes associated with postrecurrence survival. Genes positively associated with survival were predominantly immune response related (e.g., ICOS, CD3d, ZAP70, TRAT1, TARP, GZMK, LCK, CD2, CXCL13, CCL19, CCR7, VCAM1) while genes negatively associated with survival were cell proliferation related (e.g., PDE4D, CDK2, GREF1, NUSAP1, SPC24). Identification of genes associated with survival of metastatic melanoma Survival Analysis was performed using Statistical Analysis of Microarrays B D denotes same patient with multiple reccurences

ORGANISM(S): Homo sapiens

SUBMITTER: Bogunovic D

PROVIDER: S-ECPF-GEOD-19234 | biostudies-other | 2009 Dec

REPOSITORIES: biostudies-other

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Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival.

Project description:Although remission rates for metastatic melanoma are generally very poor, some patients can survive for prolonged periods following metastasis. We used gene expression profiling, mitotic index (MI), and quantification of tumor infiltrating leukocytes (TILs) and CD3+ cells in metastatic lesions to search for a molecular basis for this observation and to develop improved methods for predicting patient survival. We identified a group of 266 genes associated with postrecurrence survival. Genes positively associated with survival were predominantly immune response related (e.g., ICOS, CD3d, ZAP70, TRAT1, TARP, GZMK, LCK, CD2, CXCL13, CCL19, CCR7, VCAM1) while genes negatively associated with survival were cell proliferation related (e.g., PDE4D, CDK2, GREF1, NUSAP1, SPC24). Identification of genes associated with survival of metastatic melanoma Survival Analysis was performed using Statistical Analysis of Microarrays B D denotes same patient with multiple reccurences

2009-11-30 | E-GEOD-19234 | biostudies-arrayexpress

Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival.

Project description:Although remission rates for metastatic melanoma are generally very poor, some patients can survive for prolonged periods following metastasis. We used gene expression profiling, mitotic index (MI), and quantification of tumor infiltrating leukocytes (TILs) and CD3+ cells in metastatic lesions to search for a molecular basis for this observation and to develop improved methods for predicting patient survival. We identified a group of 266 genes associated with postrecurrence survival. Genes positively associated with survival were predominantly immune response related (e.g., ICOS, CD3d, ZAP70, TRAT1, TARP, GZMK, LCK, CD2, CXCL13, CCL19, CCR7, VCAM1) while genes negatively associated with survival were cell proliferation related (e.g., PDE4D, CDK2, GREF1, NUSAP1, SPC24). Furthermore, any of the 4 parameters (prevalidated gene expression signature, TILs, CD3, and in particular MI) improved the ability of Tumor, Node, Metastasis (TNM) staging to predict postrecurrence survival; MI was the most significant contributor (HR = 2.13, P = 0.0008). An immune response gene expression signature and presence of TILs and CD3+ cells signify immune surveillance as a mechanism for prolonged survival in these patients and indicate improved patient subcategorization beyond current TNM staging.

| S-EPMC2787158 | biostudies-literature

Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival.

2009-12-01 | GSE19234 | GEO

Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts.

Project description:IntroductionWhile Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy.MethodsEvaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders.ResultsSix proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort.DiscussionOur study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making.

| S-EPMC11249723 | biostudies-literature

Expression profile of primary and wound metastatic lesions of melanoma

Project description:The phenomenon that metastatic lesion developed on injured sites has long been recognized in a number of cancers, such as melanoma. The factors associated with wound healing that attract circulating tumor cells have remained unknown, however. A patient with acral lentiginous melanoma presented with a metastatic lesion that appeared 1 month after trauma. To explore the molecular mechanism underlying the promotion of wound metastasis in melanoma, we performed microarray analysis of the metastatic lesions (n = 2) and the primary lesions (n = 3) of the patient. Using Human Genome U133 Plus 2.0 array, we compared global gene expression profiles of tissues derived from the patient’s primary (n = 3) and wound metastatic (n = 2) lesions to search for particular biological functions in genes of which expression intensities were increased in the wound metastasic lesions of melanoma.

2015-06-26 | E-GEOD-62837 | biostudies-arrayexpress

Expression profile of primary and wound metastatic lesions of melanoma

2015-06-26 | GSE62837 | GEO

Gene expression analysis of recurrent metastatic melanoma lesions

Project description:In this study, we sought to indentify stable individual traits in developing metastatic melanoma, assess their stability in time, and analyze typical dynamics and common trends of genomic changes in individual cases of late stage metastatic cancer. To this end, we compared consecutive recurrent metastases developed by a special group of eight individuals with advanced metastatic melanoma, all developing several recurrent metastases over several months to years of natural disease evolution. Twenty-six recurrent melanoma metastases were surgically isolated from 8 patients experiencing relapse after one or more successful treatment intervention(s) with no signs of residual disease. Patients experiencing recurrent metastases were labeled with capital letters; “A”, “B”, “C”, etc., their subsequent metastases as “A/1”, “A/2”, “B/1”, “B/2”, etc., while synchronous metastases in a given patient were labeled as “A/1a”, “A/1b” etc. Another 22 melanoma cell lines isolated and maintained as above were expanded from melanoma patients with rapid disease curse, for whom only one metastasis was available. As no extended follow up was possible in these cases, the cell lines are considered representative of random time points in the natural course of metastatic melanoma. These cell lines were labeled with Arabic numbers, as “1”, “2”, ”3”, etc

| S-ECPF-GEOD-38119 | biostudies-other

Gene expression analysis of recurrent metastatic melanoma lesions

Project description:In this study, we sought to indentify stable individual traits in developing metastatic melanoma, assess their stability in time, and analyze typical dynamics and common trends of genomic changes in individual cases of late stage metastatic cancer. To this end, we compared consecutive recurrent metastases developed by a special group of eight individuals with advanced metastatic melanoma, all developing several recurrent metastases over several months to years of natural disease evolution. Twenty-six recurrent melanoma metastases were surgically isolated from 8 patients experiencing relapse after one or more successful treatment intervention(s) with no signs of residual disease. Patients experiencing recurrent metastases were labeled with capital letters; M-bM-^@M-^\AM-bM-^@M-^], M-bM-^@M-^\BM-bM-^@M-^], M-bM-^@M-^\CM-bM-^@M-^], etc., their subsequent metastases as M-bM-^@M-^\A/1M-bM-^@M-^], M-bM-^@M-^\A/2M-bM-^@M-^], M-bM-^@M-^\B/1M-bM-^@M-^], M-bM-^@M-^\B/2M-bM-^@M-^], etc., while synchronous metastases in a given patient were labeled as M-bM-^@M-^\A/1aM-bM-^@M-^], M-bM-^@M-^\A/1bM-bM-^@M-^] etc. Another 22 melanoma cell lines isolated and maintained as above were expanded from melanoma patients with rapid disease curse, for whom only one metastasis was available. As no extended follow up was possible in these cases, the cell lines are considered representative of random time points in the natural course of metastatic melanoma. These cell lines were labeled with Arabic numbers, as M-bM-^@M-^\1M-bM-^@M-^], M-bM-^@M-^\2M-bM-^@M-^], M-bM-^@M-^]3M-bM-^@M-^], etc

2013-12-31 | E-GEOD-38119 | biostudies-arrayexpress

Copy number analysis of recurrent metastatic melanoma lesions

Project description:In this study, we sought to indentify stable individual traits in developing metastatic melanoma, assess their stability in time, and analyze typical dynamics and common trends of genomic changes in individual cases of late stage metastatic cancer. To this end, we compared consecutive recurrent metastases developed by a special group of eight individuals with advanced metastatic melanoma, all developing several recurrent metastases over several months to years of natural disease evolution. Twenty-six recurrent melanoma metastases were surgically isolated from 8 patients experiencing relapse after one or more successful treatment intervention(s) with no signs of residual disease. Patients experiencing recurrent metastases were labeled with capital letters; M-bM-^@M-^\AM-bM-^@M-^], M-bM-^@M-^\BM-bM-^@M-^], M-bM-^@M-^\CM-bM-^@M-^], etc., their subsequent metastases as M-bM-^@M-^\A/1M-bM-^@M-^], M-bM-^@M-^\A/2M-bM-^@M-^], M-bM-^@M-^\B/1M-bM-^@M-^], M-bM-^@M-^\B/2M-bM-^@M-^], etc., while synchronous metastases in a given patient were labeled as M-bM-^@M-^\A/1aM-bM-^@M-^], M-bM-^@M-^\A/1bM-bM-^@M-^] etc. Another 22 melanoma cell lines isolated and maintained as above were expanded from melanoma patients with rapid disease curse, for whom only one metastasis was available. As no extended follow up was possible in these cases, the cell lines are considered representative of random time points in the natural course of metastatic melanoma. These cell lines were labeled with Arabic numbers, as M-bM-^@M-^\1M-bM-^@M-^], M-bM-^@M-^\2M-bM-^@M-^], M-bM-^@M-^]3M-bM-^@M-^], etc.

2013-12-31 | E-GEOD-38137 | biostudies-arrayexpress

Circulating immune profile can predict survival of metastatic uveal melanoma patients: results of an exploratory study.

Project description:Metastatic uveal melanoma (UM) is a poor prognosis malignancy. Immunotherapy is commonly employed, despite the low activity, considering the lack of other effective systemic treatments. In this study, the prognostic and predictive role of soluble immune checkpoints and inflammatory cytokines/chemokines in 22 metastatic UM patients was evaluated. Baseline levels of these molecules were assessed, as well as their changes during anti-PD-1 therapy. The correlation between soluble immune checkpoints/cytokines/chemokines and survival was analyzed. A comparison between circulating immune profile of metastatic cutaneous melanoma (CM), for which immunotherapy is a mainstay of treatment, and UM during anti-PD-1 therapy was also performed. Three immune molecules resulted significantly higher in metastatic UM patients with survival <6 months versus patients with survival ≥6 months: IL-8, HVEM and IDO activity. Considering these three molecules, we obtained a baseline score able to predict patients' survival. The same three molecules, together with soluble(s) CD137, sGITR and sCD27, resulted significantly lower in patients with survival >30 months. We also observed an increase of sCD137, sCD28, sPD-1, sPD-L2 sLAG3, sCD80 and sTim3 during anti-PD-1 treatment, as well as IDO activity, IP-10 and CCL2. Several of these molecules were significantly higher in UM compared to CM patients during anti-PD-1 therapy. The analysis of circulating immune molecules allows to identify patients with poor prognosis despite immunotherapy and patients with long survival treated with an anti-PD-1 agent. The different serum concentration of these molecules during anti-PD-1 therapy between UM and CM reflects the different efficacy of immune checkpoint inhibitors.

| S-EPMC9302506 | biostudies-literature

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