Plasma Exosome-Derived SENP1 May Be a Potential Prognostic Predictor for Melanoma

ObjectiveTo evaluate plasma exosome-derived SUMO-specific protease (SENP)1 levels and assess their prognostic value in melanoma.Patients and MethodsWe extracted exosomes from the plasma of 126 melanoma patients, and identified them with transmission electron microscopy, nanoparticle tracking analysis and western blotting. The plasma exosome-derived SENP1 levels of melanoma patients and healthy controls were detected with ELISA.ResultsPlasma exosome-derived SENP1 levels in melanoma patients were significantly upregulated than in healthy controls (P < 0.001). Plasma exosome-derived SENP1 levels in melanoma patients with tumor size >10 cm, located in the mucosa or viscera, with Clark level IV/V, with lymph node metastasis, and TNM stages IIb–IV were significantly higher than in patients in with tumor size <10 cm, located in the skin, with Clark level I–III, without lymph node metastasis, and TNM stages IIb–IV (all P < 0.05). Disease-free survival (DFS) and overall survival (OS) were worse in melanoma patients who had higher plasma exosome-derived SENP1 levels than lower plasma exosome-derived SENP1 levels (both P < 0.001). Area under the receiver operating characteristic curve (AUROC) of plasma exosome-derived SENP1 for predicting 3-year DFS of melanoma patients was 0.82 [95% confidence interval (CI): 0.74–0.88], with a sensitivity of 81.2% (95% CI: 69.9–89.6%) and specificity of 75.4% (95% CI: 62.2–85.9%). The AUROC of plasma exosome-derived SENP1 for predicting 3-year OS of melanoma patients was 0.76 (95% CI: 0.67–0.83), with a sensitivity of 95.7% (95% CI: 85.5–99.5%) and specificity of 62.0% (95% CI: 50.4–72.7%).ConclusionsMelanoma patients with higher plasma exosome-derived SENP1 levels had worse DFS and OS. The plasma exosome-derived SENP1 levels may be a potential prognostic predictor for 3-year DFS and 3-year OS of melanoma.

Metastasierendes malignes Melanom nach Laserung eines Pigmentmals

ZusammenfassungEine 21-jährige Patientin hatte seit Jahren ein pigmentiertes „Muttermal“ an der Schulter, das sie von einem Dermatologen mit einem Laser entfernen ließ. Ein Jahr später bildete sich erneut eine Pigmentierung an der gelaserten Stelle. Unter dem Verdacht auf ein malignes Melanom wurde die Läsion exzidiert; die Dermatohistologie bestätigte ein ulzeriertes malignes Melanom, Clark-Level IV, max. Tumordicke nach Breslow 2,4 mm. Nachdem eine Sentinel-Lymphnode-Biopsie der Axilla zunächst unauffällig war, stellte sich die Patientin nach wenigen Monaten wegen Kieferschmerzen vor, wobei sich eine osteolytische Metastase in der Mandibula zeigte. Das weitere Staging ergab multiple pulmonale, hepatische, mediastinale und weitere ossäre Metastasen. Unter einer Therapie mit Dabrafenib und Trametinib kam es nach kurzzeitiger Besserung zu einem nicht beherrschbaren Hirnödem mit Exitus letalis.In Anbetracht des tragischen Krankheitsverlaufes stellt sich die Frage nach der Vereinbarkeit der primären Lasertherapie von Pigmentmalen mit dem dermatologischen Facharztstandard. Risiken durch die Lasertherapie melanozytärer Naevuszellnaevi betreffen die mögliche Fehldiagnose eines malignen Melanoms als Naevus, welches nach Lasertherapie aufgrund des destruierenden Verfahrens nicht dermatohistologisch untersucht werden kann, die möglicherweise unvollständige Entfernung von Naevuszellen, die im Folgenden maligne entarten können, und Schwierigkeiten der klinischen Nachbeobachtung einer Läsion nach Laserung. Dysplastische Naevi sollten daher keinesfalls destruierend mit einer Lasertherapie entfernt werden; Leitlinien raten auch von einer Laserbehandlung melanozytärer Naevi ab und empfehlen, sollte einem entsprechenden Patientenwunsch doch gefolgt werden, zumindest eine Stanzbiopsie zur Diagnosesicherung durchzuführen. Ein Verzicht auf diese empfohlene diagnostische Absicherung könnte einen Befunderhebungsfehler mit der möglichen Folge einer Beweislastumkehr darstellen.

Decreased Expression of CPEB3 Predicts a Poor Prognosis in Patients with Melanoma: A Study Based on TCGA Data

Aim. Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) has been acknowledged as a tumor-suppressive gene in several cancers; however, there are few reports on the clinical significance of CPEB3 in melanoma. The aim of this study was to investigate the role of CPEB3 in predicting the prognosis of melanoma patients. Methods. The association of CPEB3 expression and clinical pathologic features was performed using The Cancer Genome Atlas (TCGA) data set. The role of CPEB3 expression in prognosis was also analyzed. In addition, CPEB3 expression-related pathways were enriched by gene set enrichment analysis (GSEA). Association analysis of CPEB3 gene expression and immune infiltration was performed by ssGSEA. Results. The mRNA was significantly less in melanoma than in normal tissues ( p < 0.001 ). The decrease in CPEB3 expression in melanoma was significantly correlated with T staging ( p < 0.001 ), clinical staging ( p = 0.029 ), melanoma Clark level ( p = 0.014 ), and melanoma ulceration ( p = 0.003 ), while it was marginally significant in N staging ( p = 0.089 ). Melanoma with low CPEB3 expression was associated with worse OS (overall survival), progression-free survival (PFS), and disease-specific survival (DSS) than in that with high expression. In the univariate analysis, expression of CPEB3, melanoma ulceration, Clark level of melanoma, age, clinical stage, T stage, and N stage were correlated with OS ( p < 0.05 ). Further analysis by multivariate Cox regression showed that N stage ( p = 0.029 ), melanoma ulceration ( p = 0.004 ), and CPEB3 expression ( p < 0.001 ) were independent prognostic factors of OS in melanoma. Moreover, GSEA showed that several pathways were enriched in CPEB3, such as PD1 signaling, CTLA4 pathway, CTCF pathway, CHEMOKIN signaling, VEGF signaling, and JAK-STAT pathway. CPEB3 was significantly correlated with the infiltration level of B cells ( p < 0.001 ), T cells ( p < 0.001 ), T helper cells ( p < 0.001 ), and central memory T (Tcm) cells ( p < 0.001 ). Conclusion. CPEB3 may be a potential prognostic marker in melanoma with poor survival. Moreover, PD1 signaling, CTLA4 pathway, CTCF pathway, CHEMOKIN signaling, VEGF signaling, and JAK-STAT pathway may be the key pathway regulated by CPEB3. Moreover, the expression of CPEB3 in melanoma is related to the level of immune infiltration.

E-Cadherin Expression in Canine Melanocytic Tumors: Histological, Immunohistochemical, and Survival Analysis

E-cadherin, a glycoprotein involved in cell-cell adhesion, has a pivotal role in epithelial-mesenchymal transition, a process through which neoplastic epithelial cells develop an invasive phenotype. In human cutaneous melanomas, decreased E-cadherin expression is associated with shorter survival and increased Breslow thickness, whereas in the dog its role is poorly understood. Tumor thickness and modified Clark level were recently proposed as useful features to assess canine melanocytic tumors, but no studies investigated their association with E-cadherin expression. We performed immunohistochemistry on 77 formalin-fixed, paraffin-embedded primary canine melanocytic tumors. A 3-tier and a 2-tier classification system for assessing E-cadherin expression were tested, with the latter being more informative for the assessment of canine melanocytic tumors. E-cadherin expression was lower in cutaneous melanomas than melanocytomas, as well as in amelanotic tumors compared to pigmented tumors. In amelanotic melanomas, absent E-cadherin expression was associated with an unfavorable outcome, suggesting a potential use of this marker in defining the prognosis of amelanotic melanomas. E-cadherin expression was lower in tumors with greater tumor thickness and modified Clark level ≥IV, suggesting its possible utility in identifying the most invasive tumors. The expression of E-cadherin in oral melanomas was heterogeneous, but was associated with pigmentation and clinical outcome; thus, E-cadherin evaluation could be advantageous to detect the most aggressive neoplasms. However, cutaneous melanomas without E-cadherin expression frequently had a favorable clinical outcome. Hence, its importance as prognostic factor should be carefully considered depending on the tumor origin.