Melanoma Research最新文献

Cutaneous malignant melanoma (CMM) is one of the most aggressive and lethal types of skin cancer. Cytoskeletal remodeling is a key factor in the progression of CMM. Previous research has shown that activating transcription factor 3 (ATF3) inhibits metastasis in bladder cancer by regulating actin cytoskeleton remodeling through gelsolin. However, whether ATF3 plays a similar role in cytoskeletal remodeling in CMM cells remains unknown. Various gene and protein expression analyses were performed using techniques such as reverse transcription quantitative PCR, western blot, immunofluorescent staining, and immunohistochemical staining. CMM viability, migration, and invasion were examined through cell counting kit-8 and transwell assays. The interactions between cell division cycle 42 (CDC42) and ATF3 were investigated using chromatin immunoprecipitation and dual-luciferase reporter assays. CDC42 was upregulated in CMM tissues and cells. Cytoskeletal remodeling of CMM cells, as well as CMM cell proliferation, migration, and invasion, were inhibited by CDC42 or ATF3. ATF3 targeted the CDC42 promoter region to regulate its transcriptional activity. ATF3 suppresses cytoskeletal remodeling in CMM cells, thereby inhibiting CMM progression and metastasis through CDC42. This research may provide a foundation for using ATF3 as a therapeutic target for CMM.

Although mucosal melanomas are rare and constitute approximately 1.4% of all melanomas, the prognosis of patients with mucosal melanoma is poorer in comparison to cutaneous melanomas. Despite their poor prognosis, limited treatment options are currently available for patients with advanced disease. These noncutaneous subtypes of melanomas are not responding to treatment used for cutaneous melanomas. We performed RNA sequencing on four mucosal melanoma samples comprising of two primary tumors and two corresponding metastases. A TRIM33 :: CSDE1 fusion was detected in both the primary tumor and metastasis of a vulvar melanoma, supporting the fusion to be a driver in oncogenesis. Vulvar melanoma is the third tumor to have been reported to harbor TRIM33 :: CSDE1 fusion. Detecting fusions may have a clinically significant impact in patients with advanced mucosal melanoma who have failed front-line immunotherapy.

Melanoma is an aggressive tumor that is challenging to treat. Talimogene laherparepvec (T-VEC), the first oncolytic virus treatment approved by the US Food and Drug Administration to treat unresectable melanoma, was recently used in recurrent tumors after initial surgery. Our network meta-analysis aimed to compare T-VEC treatment of metastatic melanoma with treatment of granulocyte-macrophage colony-stimulating factor (GM-CSF) and control group. The protocol for this network meta-analysis was retrospectively registered with PROSPERO (CRD42022363321). Three databases, namely Embase, PubMed, and Cochrane Library, were searched until 10 June 2024. The search terms used were a combination of 'metastatic melanoma', 'melanoma', 'T-VEC', 'talimogene laherparepvec', and 'GM-CSF'. Seven studies, with 978 participants receiving T-VEC treatment, 649 participants receiving GM-CSF treatment, and 938 participants constituting the control group, were included in our meta-analysis. For 1-year overall survival (OS), the league table revealed significant differences between the control and T-VEC groups [0.90 (0.83, 0.99)]. The disease-free survival (DFS) over 2 years was also analyzed showing no difference between the groups in DFS in the league table. T-VEC may be a favorable treatment for metastatic melanoma owing to the notable increase in OS. Nevertheless, due to the side effects and limitations, the clinical benefits of T-VEC therapy in metastatic melanoma should be interpreted cautiously. This network meta-analysis demonstrates that T-VEC may be a favorable choice of treatment for metastatic melanoma.

Vulvar and vaginal melanomas (VVMs) are rare malignancies, but they are relatively more common among Asian women. This makes the collection of data on VVMs in this population crucial. Moreover, no cohort studies have examined and compared the effects of immune checkpoint inhibitors (ICIs) on VVM in Asian women. Therefore, we aimed to investigate the clinical characteristics of VVMs in Japanese women and the effects of ICI treatment. This single-center, retrospective cohort study included patients who were histologically diagnosed with VVM at our hospital between March 2005 and December 2023. The Kaplan-Meier analysis was used to compare the prognosis of vulvar melanoma (VuM) and vaginal melanoma (VaM) throughout entire treatments and compare the efficacies of ICIs and conventional chemotherapies in VVM. In total, 28 women with VuM ( n  = 14) and VaM ( n  = 14) were included. There were no significant differences in overall survival (OS) [median OS: not reached (95% confidence interval (CI), 13.2-NA) vs. 30.2 months (95% CI, 23.2-NA), log-rank test, P  = 0.456] between the VuM and VaM groups. The progression-free survival (median progression-free survival: 14.7 vs. 5.2 months, P  = 0.002) and OS (median OS: 33.8 vs. 7.2 months, P  < 0.001) were significantly better for the ICI-treated group than for the conventional chemotherapy-treated group in VVM. The prognosis of patients with VVM improved significantly with the advent of ICI, demonstrating the importance of ICI in the treatment of VVM.

Immunotherapy treatments that target programmed cell death receptor-1 (PD-1) or its ligand (PD-L1) have revolutionized the treatment of metastatic melanoma and currently represent the standard first-line treatment for this type of cancer. However, it is still not entirely clear which biomarkers are cost-effective, simple, and highly reliable. This systematic review and meta-analysis aims to analyze the predictive value of the baseline neutrophil-lymphocyte ratio (NLR) regarding disease progression and overall survival of patients with metastatic melanoma undergoing treatment with PD-1/PD-L1 blockade. PubMed, Scopus, and Web of Science were searched for studies comparing high versus low NLR. We performed the meta-analysis using RStudio v4.4.2 software. A total of 20 studies and 2691 patients were included, all with diagnoses of melanoma. The majority of the individuals were male 2278 (84, 65%). The median overall survival (OS) and progression-free survival (PFS) ranged from 5.0 to 44.4 and from 1.8 to 15.0 months, respectively. Compared with the high NLR ratio, the low exposure group achieved better rates of OS [hazard ratio (HR), 2.07; 95% CI, 1.73-2.48; P  < 0.00001; I ² = 47%]. Regarding PFS, there was a statistically significant difference between groups with tendencies toward the low NLR exposure group (HR, 1.59; 95% CI, 1.39-1.81; P  < 0.00001; I²=31%]. This systematic review and meta-analysis revealed significant lower OS in melanoma patients treated with PD-1/PD-L1 blockade who had elevated baseline NLR values. Furthermore, an increased PFS was observed in patients with a lower baseline NLR value. This study highlights NLR as an important prognostic biomarker for patients with metastatic melanoma who are candidates for treatment with PD-1 and PD-L1.

This systematic review aims to evaluate the prevalence of reductions in psychosocial wellbeing among patient with melanoma in situ (MIS). It also aims to identify factors associated with psychosocial reactions, the instruments used to measure psychosocial outcomes, and to evaluate existing intervention programs for supporting this population. Search strategies for different databases including PubMed, Embase, Scopus, PsycINFO, and Web of Science were designed and implemented. A total of 2378 records were identified, resulting in 22 included papers. Various aspects of psychosocial wellbeing were evaluated in the reviewed articles, with fear of cancer recurrence being the most frequently investigated among patients diagnosed with melanoma. Only 2 of the 22 studies reported data for MIS patients, indicating no significant difference in psychosocial welling between patients with MIS and those at higher stages. Regarding interventional support, there is a notable lack of interventions specifically addressing the psychosocial needs of MIS patients. Our findings highlight a significant research gap on psychosocial wellbeing following a MIS diagnosis and suggest a shortage of targeted psychosocial interventions for this growing patient population. The observed variability in measuring psychosocial aspects presents challenges in identifying the essential components of effective interventions. Future research should prioritize employing mixed methodologies and addressing the unique needs of MIS patients.

Pediatric melanoma is the most common skin cancer in children and treatment relies on accurate staging. The American Academy of Dermatology recommends excisional biopsy for suspicious skin lesions, however, partial shave biopsies are often performed, the impact of which is unknown in pediatric and adolescent/young adult (AYA) patients. The aim of this retrospective case series study was to evaluate the impact of the diagnostic biopsy method on staging, treatment, and treatment-related outcomes in pediatric/AYA patients with melanoma. Among 103 pediatric/AYA patients with atypical cutaneous melanocytic lesions, the most common biopsy method was partial shave (68/103, 66.0%) followed by punch (20/103, 19.4%), excisional (14/103, 13.6%), and incisional nonshave (1/103, 1%). Over half of all biopsies yielded a positive deep margin, reflecting compromised microstaging (56/103, 55.4%), the majority occurred following partial shave (52/56, 92.9%) compared with other techniques ( P  < 0.001). All 11 patients with wider surgical target margins of wide local excision and 8/9 patients with sentinel lymph node biopsy performed due to positive deep margin, underwent a partial shave biopsy ( P  = 0.05 and 0.32, respectively). Almost half of all patients who underwent partial shave biopsy had a clinically suspected abnormal melanocytic tumor prior to biopsy (31/68, 45.6%; P  = 0.03). Of 56 patients who had compromised microstaging, 17 (30.4%) had a diagnosis of melanoma ( P  = 0.17). Pediatric/AYA patients frequently undergo partial shave biopsy, which is associated with more invasive definitive surgical treatment due to compromised microstaging. These results may help optimize care of patients with cutaneous melanocytic tumors.

The aim of the study is to use the Surveillance, Epidemiology, and End Results (SEER) database to develop a useful clinical nomogram that uses prognosis prediction for pediatric melanoma patients. We obtained clinical information on pediatric melanoma patients from the SEER database between 2000 and 2018. Each patient was split into a training cohort or a validation cohort at random. Results between various subgroups were compared using Kaplan-Meier analyses. We created a nomogram to calculate the probability of survival for pediatric patients with melanoma. The performance of nomograms was assessed using calibration and discrimination. To assess the clinical use of this newly created model, decision curve analysis was also performed. In this study, a total of 890 eligible patients were chosen at random and allocated to 70% of training cohorts ( n  = 623) and 30% of validation cohorts ( n  = 267). After applying the chosen various components to create a nomogram, validated indexes showed that the nomogram had a strong capacity for discrimination. The training set's and validation set's C-index values were 0.817 and 0.832, respectively. The calibration plots demonstrated a strong correlation between the observation and the forecast. The model has a good clinical net benefit for pediatric melanoma patients, according to the clinical decision curve. In conclusion, we created an effective survival prediction model for pediatric melanoma. This nomogram is accurate and useful for clinical decision-making. Still, more external confirmation is required.

Anorectal melanoma (ARM) is a rare malignancy often associated with a poor prognosis due to its late diagnosis and aggressive biological behavior. This review aims to comprehensively investigate ARM's diagnosis, management, and treatment, emphasizing its clinical characteristics, laboratory findings, and implications for patient prognosis. A systematic literature search was conducted in PubMed, Embase, and Cochrane CENTRAL databases from inception to 1 July 2024. This review synthesizes existing literature to provide a comprehensive understanding of this rare primary malignancy. A total of 110 articles reporting on 166 patients were included. Gender data were available for 131 cases, comprising 67 females (51.1%) and 64 males (48.9%). The median age was 66 years. The overall median time to diagnosis was 4 months for anal melanoma, 3 months for rectal melanoma, and 4 months for anorectal junction melanoma. The clinical presentation was nodular in 98.2% of cases. Pre-diagnosis symptoms included bleeding in 84.9% of cases, mucous elimination (6%), pain (68.7%), tenesmus (16.9%), and changes in bowel movements (28.5%). Overall survival (OS) was reported in 82 cases, with a median OS of 11 months: 11 months for anal melanoma, 7 months for rectal melanoma, and 12 months for anorectal junction melanoma. ARM is a rare and aggressive melanoma subtype often diagnosed at an advanced stage, leading to a poor prognosis. A female predominance was observed, consistent with other mucosal melanomas. Anal melanoma exhibited better progression-free survival, and OS compared to rectal and anorectal junction melanoma.