Author Correction: Tumour gene expression signature in primary melanoma predicts long-term outcomes.
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ABSTRACT:
SUBMITTER: Garg M
PROVIDER: S-EPMC9114317 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
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Author Correction: Tumour gene expression signature in primary melanoma predicts long-term outcomes.
Garg Manik M Couturier Dominique-Laurent DL Nsengimana Jérémie J Fonseca Nuno A NA Wongchenko Matthew M Yan Yibing Y Lauss Martin M Jönsson Göran B GB Newton-Bishop Julia J Parkinson Christine C Middleton Mark R MR Bishop D Timothy DT McDonald Sarah S Stefanos Nikki N Tadross John J Vergara Ismael A IA Lo Serigne S Newell Felicity F Wilmott James S JS Thompson John F JF Long Georgina V GV Scolyer Richard A RA Corrie Pippa P Adams David J DJ Brazma Alvis A Rabbie Roy R
Nature communications 20220517 1
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Project description:Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We use differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR = 1.63, p = 5.24 × 10-5) and overall survival (HR = 1.61, p = 1.67 × 10-4), was validated in 175 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC = 7.03 × 10-4), or published prognostic signatures (pAUROC < 0.05). The signature score negatively correlated with measures of immune cell infiltration (ρ = -0.75, p < 2.2 × 10-16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.
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Project description:Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We used differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR=1.63, p=5.24x10-5) and overall survival (HR=1.61, p=1.67x10-4), and validated in 177 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC=0.02), or published prognostic signatures. The signature score negatively correlated with measures of immune cell infiltration (ÃÂ=-0.75, p<2.2x10-16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.
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Project description:PurposeTo develop a prognostic test based on a single blood sample obtained at the time of uveal melanoma diagnosis.Methods83 patients diagnosed with posterior uveal melanoma between 1996 and 2000 were included. Peripheral serum samples were obtained at diagnosis and kept at -80 °C until this analysis. Protein profiling of 84 cancer-related proteins was used to screen for potential biomarkers and a prognostic test that stratifies patients into metastatic risk categories was developed (serUM-Px) in a training cohort and then tested in a validation cohort.ResultsLow serum leptin levels and high osteopontin levels were found to identify patients with poor prognosis and were therefore selected for inclusion in the final test. In the validation cohort, patient sex and American Joint Committee on Cancer stages were similarly distributed between the low, intermediate, and high metastatic risk categories. With increasing metastatic risk category, patients had shorter metastasis-free- and overall survival, as well as greater cumulative incidence of uveal melanoma-related mortality in competing risk analysis (P = 0.007, 0.018 and 0.029, respectively). In multivariate Cox regression, serUM-Px was an independent predictor of metastasis with tumor size and patient sex as covariates (hazard ratio 3.2, 95% CI 1.5-6.9).ConclusionsA prognostic test based on a single peripheral venous blood sample at the time of uveal melanoma diagnosis stratifies patients into low, intermediate, and high metastatic risk categories. Prospective validation will facilitate its clinical utility.
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Project description:PurposeGlioblastoma (GBM) is the most common malignant primary brain tumor with a dismal prognosis of less than 2 years under maximal therapy. Despite the poor prognosis, small fractions of GBM patients seem to have a markedly longer survival than the vast majority of patients. Recently discovered intertumoral heterogeneity is thought to be responsible for this peculiarity, although the exact underlying mechanisms remain largely unknown. Here, we investigated the epigenetic contribution to survival.MethodsGBM treatment-naïve samples from 53 patients, consisting of 12 extremely long-term survivors (eLTS) patients and 41 median-term survivors (MTS) patients, were collected for DNA methylation analysis. 865 859 CpG sites were examined and processed for detection of differentially methylated CpG positions (DMP) and regions (DMR) between both survival groups. Gene Ontology (GO) and pathway functional annotations were used to identify associated biological processes. Verification of these findings was done using The Cancer Genome Atlas (TCGA) database.ResultsWe identified 67 DMPs and 5 DMRs that were associated with genes and pathways - namely reduced interferon beta signaling, in MAPK signaling and in NTRK signaling - which play a role in survival in GBM.ConclusionIn conclusion, baseline DNA methylation differences already present in treatment-naïve GBM samples are part of genes and pathways that play a role in the survival of these tumor types and therefore may explain part of the intrinsic heterogeneity that determines prognosis in GBM patients.
| S-EPMC11341684 | biostudies-literature
Project description:PurposeIn partially accommodative esotropia (PAET), prism glasses can correct small angles of residual esotropia but the long-term effect of prismatic correction alone without surgery has not been reported. We aimed to investigate the long-term outcome of prism glasses after full hypermetropic correction for PAET.MethodsThis retrospective, case-control study was performed for children aged 10 years or younger with a residual esotropia of ≤ 20 prism diopters (PD) after full hypermetropic correction who were fitted with prism glasses and followed-up for 3 years or more. Clinical characteristics and the angle of esodeviation were obtained at each follow-up examination. Successful motor outcome after 3 years of prismatic correction was determined if the residual angle of esotropia after full hypermetropic correction was ≤ 10PD. Patients who eventually weaned off prism glasses were noted.ResultsAmong 124 patients, 30.6% achieved success and 7.3% weaned off prism glasses after 3 years of prism-wear. Smaller amount of latent esodeviation (P = 0.001) revealed by prism adaptation and good fusional response at near with the Worth 4-dot test were significant prognostic factors of success by multivariate analysis (P = 0.033). After 3 years of wearing prism glasses, the rate of improvement in stereoacuity was higher in the Success group (60.5% vs 27.9%) (P = 0.001), however, there was no significant difference between the prism-weaned group and prism-wearing group within the Success group (P>0.05).ConclusionPrism glasses for small angle PAET can be a treatment option in patients who have a small angle of latent esodeviation revealed by prism adaptation and good sensory fusion at near. Otherwise, early surgery may be advisable as the majority of patients showed suboptimal outcome even after long-term prism-wear.
| S-EPMC6886759 | biostudies-literature
Project description:PurposeBrain metastasis is the major cause of mortality among patients with melanoma. A molecular prognostic test that can reliably stratify patients at initial melanoma diagnosis by risk of developing brain metastasis may inform the clinical management of these patients.Experimental designWe performed a retrospective, cohort-based study analyzing genome-wide and targeted microRNA expression profiling of primary melanoma tumors of three patient cohorts (n = 92, 119, and 45) with extensive clinical follow-up. We used Cox regression analysis to establish a microRNA-based signature that improves the ability of the current clinicopathologic staging system to predict the development of brain metastasis.ResultsOur analyses identified a 4-microRNA (miR-150-5p, miR-15b-5p, miR-16-5p, and miR-374b-3p) prognostic signature that, in combination with stage, distinguished primary melanomas that metastasized to the brain from nonrecurrent and non-brain metastatic primary tumors (training cohort: C-index = 81.4%, validation cohort: C-index = 67.4%, independent cohort: C-index = 76.9%). Corresponding Kaplan-Meier curves of high- versus low-risk patients displayed a clear separation in brain metastasis-free and overall survival (training: P < 0.001; P < 0.001, validation: P = 0.033; P = 0.007, independent: P = 0.021; P = 0.022, respectively). Finally, of the microRNA in the prognostic model, we found that the expression of a key lymphocyte miRNA, miR-150-5p, which is less abundant in primary melanomas metastatic to brain, correlated with presence of CD45(+) tumor-infiltrating lymphocytes.ConclusionsA prognostic assay based on the described miRNA expression signature combined with the currently used staging criteria may improve accuracy of primary melanoma patient prognoses and aid clinical management of patients, including selection for adjuvant treatment or clinical trials of adjuvant therapies.
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