Outcome In Melanoma Research Articles

Robot-assisted pelvic node dissection has similar operative and melanoma outcomes to open pelvic node dissection with shorter hospital stays

Background: Robot-assisted pelvic lymph node dissection (rPLND) has been employed for the surgical management of enlarged lymph nodes to reduce treatment related morbidity. With the adoption of adjuvant systemic therapy in melanoma reducing surgical indications, we set out to investigate its benefits and long-term outcomes compared to open pelvic lymph node dissection (oPLND).

The Impact of Cytotoxic T-lymphocyte Antigen-4 Genetic Polymorphisms on the Effectiveness of Ipilimumab and Patients’ Outcome in Melanoma

Precision medicine is shaping the way medicine is being practiced, pharmacogenomics is the centerpiece of precision medicine. As in several fields, researchers are investigating the role of pharmacogenomic tests in the treatment of melanoma. One of these efforts is the ongoing preclinical and clinical trials investigating the impact of the genetic polymorphism of cytotoxic T-lymphocyte antigen-4 on drugs used in melanoma treatment. This paper reviews ipilimumab as a promising treatment for melanoma and how pharmacogenomic tests can substantially impact utilizing this drug in the treatment plan, whether as a solo treatment or in conjugation with other therapies. In this review, various databases and electronic libraries were utilized to search for and review different journal articles and papers about pharmacogenomic tests for ipilimumab. Although some results showed a minimal effect, most of the results revealed that pharmacogenomic tests for ipilimumab could play a crucial role in patients’ outcomes. Further clinical trials are, however, needed on a larger scale to adopt this therapy in practice.

Treatment outcomes of mucosal melanoma of head and neck: Efficacy of immune checkpoint inhibitors for advanced disease.

Head and neck mucosal melanoma (HNMM) is a rare and aggressive subtype of melanoma. HNMM often develops as a recurrent or metastatic disease, and its prognosis is worse than that of cutaneous melanoma. Recent large-scale clinical studies have reported favorable outcomes with immune checkpoint inhibitors (ICIs) for melanoma. However, these clinical trials included only a small number of HNMM cases. This study aimed to estimate treatment outcomes and prognostic predictors of ICIs for advanced HNMM. Cases of advanced HNMM, defined as unresectable or metastatic HNMM at the initial diagnosis (five patients) or development of recurrent/metastatic HNMM after initial treatment (27 patients), were included in this study. Survival analysis and a search for prognostic factors were performed for these 32 patients. Furthermore, the detailed clinical course of patients who received ICI treatment was investigated. The median overall survival (OS) of 32 patients with advanced HNMM was 25.3 months. The estimated 1-, 3-, and 5-year OS rates were 68.4%, 42.8%, and 34.3%, respectively. Fourteen patients (43.7%) received ICIs, whereas 18 (56.3%) did not. Univariate analysis showed that ICI treatment was the only factor associated with a better 1-year OS. Patients who received ICI treatment had significantly longer OS (median OS: not reached, 1-year OS: 85.7%) than those who did not (median OS: 11.3 months, 1-year OS: 54.5%). The overall response and disease control rates of patients who received ICI treatment were 50% and 64.3%, respectively. Patients who achieved complete response (CR) or partial response (PR) to ICI treatment survived significantly longer (1-year OS: 100%) than those who did not (1-year OS: 71.4%). Among the five patients who discontinued ICI treatment due to severe immune-related adverse events (irAEs), four did not receive salvage treatments but showed durable treatment effects and survived for 9.8-54.2 months at the end of the follow-up period. ICI treatment achieved a favorable OS for advanced HNMM. CR/PR to ICI treatment and discontinuation owing to severe irAEs were favorable predictors of OS.

Impact of systemic therapies in metastatic melanoma of unknown primary: A study from MELBASE, a French multicentric prospective cohort

Clinical outcomes of advanced melanoma of unknown primary (MUP) in the era of novel therapies have been scarcely studied. To investigate the efficacy and safety of systemic treatments in patients with advanced MUP compared to patients with stage-matched melanoma of known cutaneous primary (cMKP). Based on the nationwide MelBase prospective database, this study included advanced melanoma patients treated from March 2013 to June 2021 with first-line immunotherapies, targeted therapies, or chemotherapy. Co-primary outcomes were progression-free survival and overall survival. Secondary outcome was treatment-related toxicities. Multivariate and propensity score analyses were performed. Of 1882 patients, 265 (14.1%) had advanced MUP. Patients with advanced MUP displayed more often unfavorable initial prognostic factors than those with cMKP. Progression-free and overall survival did not differ significantly between the groups (P = .73 and P = .93, respectively), as well as treatment-related toxicity rate and severity, regardless of treatment type. No record of standard diagnostic criteria of MUP used in the participating centers. Although patients with MUP had less favorable baseline prognostic factors, they benefited from the novel therapies as much as those with cMKP. They should be managed according to similar strategies.

Prognostic Relevance of Type 2 Diabetes and Metformin Treatment in Head and Neck Melanoma: Results from a Population-Based Cohort Study

Type 2 Diabetes (DM2) and the consecutively daily use of antidiabetic medication are characterized by a frequent prevalence worldwide and were shown to impact the initiation and progression of malignant diseases. While these effects were observed in a variety of malignancies, comprehensive data about the role of DM2 and antidiabetic drugs in the outcome of head and neck melanoma (HNM) patients are missing. This retrospective population-based cohort study included 382 HNM patients from Eastern Bavaria having received tumor resection to negative margins between 2010 and 2017. Recurrence-free survival (RFS) was evaluated with regard to DM2 and routine metformin intake. Statistical analysis was performed by uni- and multivariate analyses. The median follow-up time was 5.6 years. DM2 was diagnosed in 68 patients (17.8%), routine metformin intake was found in 39 cases (10.2%). The univariate survival analysis revealed impaired 5-year RFS in HNM patients with DM2 compared to non-diabetic controls (p = 0.016; 64.0% and 74.5%, respectively). The multivariate Cox regression substantiated this effect (HR = 1.980, 95% CI = 1.108-3.538, p = 0.021). In detail, the cumulative locoregional recurrence rate displayed the most far-reaching negative effect on the RFS of diabetic HNM patients (HR = 4.173, 95% CI = 1.628-10.697, p = 0.003). For metformin intake, a profound positive effect on the RFS in multivariate statistics was observed, both in the complete cohort (HR = 0.396, 95% CI = 0.177-0.884, p = 0.024) as well as in the cohort of diabetic HNM patients (HR = 0.352, 95% CI = 0.135-0.913, p = 0.032). This study emphasizes that DM2 is a relevant comorbid condition in HNM patients, impairing patient survival. Metformin intake was associated with a favorable outcome in HNM patients, providing possible therapeutic implications for future adjuvant treatment regimes.

IL7 genetic variation and toxicity to immune checkpoint blockade in patients with melanoma

Treatment with immune checkpoint blockade (ICB) frequently triggers immune-related adverse events (irAEs), causing considerable morbidity. In 214 patients receiving ICB for melanoma, we observed increased severe irAE risk in minor allele carriers of rs16906115, intronic to IL7. We found that rs16906115 forms a B cell-specific expression quantitative trait locus (eQTL) to IL7 in patients. Patients carrying the risk allele demonstrate increased pre-treatment B cell IL7 expression, which independently associates with irAE risk, divergent immunoglobulin expression and more B cell receptor mutations. Consistent with the role of IL-7 in T cell development, risk allele carriers have distinct ICB-induced CD8+ T cell subset responses, skewing of T cell clonality and greater proportional repertoire occupancy by large clones. Finally, analysis of TCGA data suggests that risk allele carriers independently have improved melanoma survival. These observations highlight key roles for B cells and IL-7 in both ICB response and toxicity and clinical outcomes in melanoma.

239P Survival outcomes predicted by irAEs on 18F-FDG-PET in response to PD-1 antibody therapy in metastatic melanoma

PD-1 antibody therapy has revolutionised the landscape of metastatic cutaneous melanoma treatments and outcomes. The aim of our study is to investigate whether immune related adverse events (irAEs) or granulomatous/reactive nodal changes visible on 18F-FDG-PET during treatment with PD-1 antibody therapy for metastatic cutaneous melanoma predicts improved overall survival.

Fatty Acid Synthase Mutations Predict Favorable Immune Checkpoint Inhibitor Outcome and Response in Melanoma and Non-Small Cell Lung Cancer Patients.

Fatty acid synthase (FASN) acts as the central member in fatty acid synthesis and metabolism processes, which regulate oncogenic signals and tumor immunogenicity. To date, no studies have reported the connection of FASN mutations with ICI efficacy. In this study, from 631 melanoma and 109 NSCLC patients who received ICI treatments, we retrospectively curated multiomics profiles and ICI treatment data. We also explored the potential molecular biological mechanisms behind FASN alterations. In melanoma patients, FASN mutations were observed to associate with a preferable immunotherapeutic prognosis and response rate (both p < 0.01). These connections were further corroborated by the NSCLC patients (both p < 0.01). Further analyses showed that a favorable tumor immunogenicity and immune microenvironment were involved in FASN mutations. This work confirms the clinical immunotherapy implications of FASN mutation-mediated fatty acid metabolism and provides a possible indicator for immunotherapy prognosis prediction.

TCR CDR3-antigen chemical complementarity associated with poor ovarian cancer outcomes: A vestigial immune response to early cancer antigens?

Ovarian cancer continues to present significant challenges for early detection and treatment, indicating a need for novel approaches to improve disease outcomes. In this report, we applied a previously described algorithm for detecting chemical complementarity between candidate cancer antigens and complementarity determining region-3 (CDR3) amino acid sequences from tumor resident T-cell receptors. Current literature indicates an association between high CDR3-cancer antigen complementarity and improved survival outcomes. For example, high CDR3-BRAF electrostatic complementarity is associated with a better melanoma outcome. However, such CDR3-cancer antigen chemical complementarity in ovarian cancer was largely associated with worse outcomes. Specifically, high CDR3-MAGEB4 and CDR3-TDRD1 electrostatic complementarity was associated with lower ovarian cancer disease free survival (DFS). Additionally, high CDR3-MAGEB4 and CDR3-TDRD1 electrostatic complementarity was associated with decreased MAGEB4/TDRD1 gene expression and gene copy numbers, consistent with a selection against ovarian cancer cells expressing these antigens. However, when TDRD1 was split into fragments, high CDR3-TDRD1 hydrophobicity complementarity, for a specific TDRD1 fragment, was associated with increased DFS and higher immune marker expression levels. This dichotomy highlights the myriad of opportunities to establish risk stratifications and to identify potential, actionable cancer antigens using immunogenomic parameters.

416P Survival outcomes predicted by irAEs on 18F-FDG-PET in response to PD-1 antibody therapy in metastatic melanoma

PD-1 antibody therapy has revolutionised the landscape of metastatic melanoma treatments and outcomes. The aim of our study is to investigate whether immune related adverse events (irAEs) or granulomatous/reactive nodal changes visible on 18F-FDG-PET during treatment with PD-1 antibody therapy for metastatic melanoma predicts improved overall survival.

Impact of Bone Metastases on Patients with Renal Cell Carcinoma or Melanoma Treated with Combotherapy Ipilimumab Plus Nivolumab.

(1) Background: Ipilimumab plus nivolumab (combo-ICI) improves overall survival (OS) in patients with advanced renal cell carcinoma (RCC) or melanoma. The impact of bone metastases (BM) on survival outcomes of combo-ICI-treated patients is unknown. (2) Methods: This single-center retrospective observational study involved 36 combo-ICI-treated patients with advanced RCC and 35 with melanoma. Clinical and laboratory data preceding the initiation of combo-ICI were collected. Univariate and multivariate Cox proportional hazard models were used to assess the effect of BM on overall survival (OS) and progression-free survival (PFS). (3) Results: zNine RCC and 11 melanoma patients had baseline BM. In unadjusted analysis, baseline BM was associated with a poorer OS in the RCC cohort. Baseline BM did not have any impact on survival outcomes in melanoma patients. After adjustment on baseline performance status and on neutrophil-to-lymphocyte ratio (NLR), the impact of BM was no longer significant, but a NLR ≥ 3 was significantly associated with a poorer OS in the RCC cohort. (4) Conclusions: The presence of baseline BM seems to be associated with worse outcomes in RCC combo-ICI-treated patients, while its effect might not be independent from the inflammatory state (approximated by the NLR). BM seems to have no impact on the outcomes of melanoma combo-ICI-treated patients.

Geographic disparities in access to immunotherapy clinical trials for metastatic melanoma.

Survival outcomes for metastatic melanoma have drastically improved with the advent of immunotherapy. Access to ongoing immunotherapy clinical trials has become increasingly important to patients with advanced disease. We sought to quantify geographic disparities in access to these trials by U.S. division, region, urban/rural status, and median income. We searched ClinicalTrials.gov for interventional immunotherapy trials for metastatic melanoma from 2015 to 2021 and identified U.S. zip codes for each participating trial site. ArcGIS was used to calculate the one-way driving time from each zip code to the nearest treatment center. Melanoma burden in each zip code outside a 60min driving radius was calculated by multiplying population by the corresponding state's cancer-specific mortality rate. χ2 tests were used to test for significance between census regions, divisions, and urban vs. rural zip codes, while logistic regression was used to quantify risk of poor access with median income. Across 148 trials, 4844 treatment centers were located in 1102 unique zip codes. 9010 zip codes were located greater than one-hour driving time from the nearest clinical trial. Southern regions were most likely to have poor access of all regions (p < 0.001), and rural status also significantly correlated with poor access (p < 0.001). For every $10,000 increase in median income, the likelihood of a zip code being within 60min from a trial increased by 1.315. While immunotherapy continue to improve survival outcomes for metastatic melanoma, geographic access to clinical trials investigating these therapies remains a challenge for a significant proportion of the U.S. population.

Genomic landscape of the immunogenicity regulation in skin melanomas with diverse tumor mutation burden.

Skin melanoma cells are tightly interconnected with their tumor microenvironment (TME), which influences their initiation, progression, and sensitivity/resistance to therapeutic interventions. An immune-active TME favors patient response to immune checkpoint inhibition (ICI), but not all patients respond to therapy. Here, we assessed differential gene expression in primary and metastatic tumors from the TCGA-SKCM dataset, compared to normal skin samples from the GTEx project and validated key findings across 4 independent GEO datasets, as well as using immunohistochemistry in independent patient cohorts. We focused our attention on examining the expression of various immune receptors, immune-cell fractions, immune-related signatures and mutational signatures across cutaneous melanomas with diverse tumor mutation burdens (TMB). Globally, the expression of most immunoreceptors correlated with patient survival, but did not differ between TMBhigh and TMBlow tumors. Melanomas were enriched in "naive T-cell", "effector memory T-cell", "exhausted T-cell", "resting Treg T-cell" and "Th1-like" signatures, irrespective of their BRAF, NF1 or RAS mutational status. Somatic mutations in IDO1 and HLA-DRA were frequent and could be involved in hindering patient response to ICI therapies. We finally analyzed transcriptome profiles of ICI-treated patients and associated their response with high levels of IFNγ, Merck18, CD274, CD8, and low levels of myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs) and M2 macrophages, irrespective of their TMB status. Overall, our findings highlight the importance of pre-existing T-cell immunity in ICI therapeutic outcomes in skin melanoma and suggest that TMBlow patients could also benefit from such therapies.

Novel IKZF3 transcriptomic signature correlates with positive outcomes of skin cutaneous melanoma: A pan-cancer analysis.

To investigate the potential relationship between Ikaros family genes and skin cutaneous melanoma (SKCM), we undertook a pan-cancer analysis of the transcriptional signature and clinical data of melanoma through multiple databases. First, 10,327 transcriptomic samples from different cancers were included to determine the overall characteristics and clinical prognoses associated with Ikaros gene expression across cancer types. Second, differentially expressed genes analysis, prognostic evaluation, and gene set enrichment analysis were employed to investigate the role of Ikaros (IKZF) genes in SKCM. Third, we evaluated the relationship between Ikaros family genes and SKCM immune infiltrates and verified the findings using the GEO single-cell sequencing dataset. The results show that Ikaros genes were widely expressed among different cancer types with independently similar patterns as follows: 1. IKZF1 and IKZF3, and 2. IKZF2 and IKZF4-5. IKZF2 and IKZF5 were downregulated in the primary tumor, and IKZF1-3 expression decreased significantly as the T-stage or metastasis increased in SKCM. Moreover, high IKZF1-3 expression was associated with better overall survival, disease-specific survival, and progression-free interval. IKZF3 is an independent prognostic factor of SKCM. Among Ikaros genes, the expression of IKZF1 and IKZF3 positively correlated with the infiltration level of CD4+ T cells and CD8+ T cells, B cells, and Tregs in SKCM and negatively correlated with the infiltration level of M0 and M1 macrophages. Moreover, single-cell sequencing data analysis revealed that IKZF1 and IKZF3 were mainly expressed by immune cells. Correlation analysis shows the immune factors and drug responses associated with IKZF3 expression. In conclusion, the present study is the first, to our knowledge, to identify a pan-cancer genomic signature of the Ikaros gene family among different cancers. Expression of these family members, particularly high levels of IKZF3, indicate positive immunological status and beneficial clinical outcomes of SKCM. IKZF3 may therefore serve as potential targets for immunotherapy of melanoma.

Gynecologic Melanoma: A 25-Year Institutional Experience

<h3>Purpose/Objective(s)</h3> Melanoma of the gynecologic tract is a rare malignancy with poor outcomes. We sought to describe clinicopathological features, patterns of care, and outcomes in a large cohort of patients (pts) with this diagnosis treated at our institution. <h3>Materials/Methods</h3> Using an institutional pathology database we identified 141 pts with gynecologic melanoma treated 1995-2021. Clinicopathologic variables were described and time to outcome was calculated by the Kaplan-Meier method. <h3>Results</h3> Median age was 62 years (IQR 54-70). Primary tumors were located at the vulva (n=97, 69%), vagina (n=34, 24%) or cervix (n=10, 7%). Of the 123 pts with known primary tumor pathology, median tumor thickness was 5.0 mm (IQR 1.8-7.1 mm), 72% had ulceration (n=88), 21% had PNI (n=26), 28% had LVI (n=35), 6% had microsatellitosis (n=7) and 42% had a component of melanoma-in-situ (MIS, n=52) with 15% (n=21) having multifocal disease at presentation. Most pts had locally confined disease at diagnosis (n=110, 78%). Nine percent (n=13) had clinically involved nodes without distant metastasis (DM) and 13% had DM (n=18). At presentation 29 pts (21%) had unresectable disease, 2 of whom had surgery after response to neoadjuvant systemic therapy. Of the 112 pts with resectable disease, 77% (n=86) had nodal sampling with 40% of those (n=34) having pathologically positive nodes. Of the 105 pts with known margins: 47% R0 (n=49), 29% MIS+ (n=30), 21% R1 (n=22) and 4% R2 (n=4). Twenty-seven pts (23% resected) received neoadjuvant systemic therapy (11 pts at diagnosis and 16 pts at recurrence). Immune checkpoint inhibitors (ICI) were the most common class (67%, n=18). Ten pts (37%) had imaging or pathologic evidence of response to neoadjuvant therapy (6 ICI, 2 chemotherapy and 2 targeted therapy). Forty-three pts (37% resected) received adjuvant systemic therapy at the time of initial resection. Thirty-nine pts (28%) received pelvic RT during their treatment course. The primary tumor bed was the target for all except 2 pts who received RT to unilateral inguinal nodes and 1 pt who received RT to a pelvic sidewall mass. The timing of RT was: 1 neoadjuvant (3%), 15 adjuvant (38%), 14 to gross disease without DM (36%) and 9 to gross disease with DM (23%). The most common adjuvant regimens were 30 Gy in 5 fractions (n=6) or 48 Gy in 20 fractions (n=3). Of 141 pts, 79 (56%) were diagnosed after 2014, the era during which ICI were used. Median follow-up of those diagnosed pre-2014 was 98 months (mo, IQR 54-111 mo) and post-2014 was 39 mo (IQR 26-50 mo). Pre- vs. post-2014 3-year actuarial event rates were not significantly different with 59% vs. 49% local control (p=0.52); 56% vs. 60% nodal control (p=0.78); 45% vs. 34% DM-free survival (p=0.11); 25% vs. 20% disease-free survival; and 55% vs. 56% melanoma-specific survival (p=0.55). <h3>Conclusion</h3> Gynecologic tract melanoma outcomes continue to be poor with a significant need for improved treatment options, both in terms of pelvic and distant disease control.

Long-Term Toxicities of Immune Checkpoint Inhibitor (ICI) in Melanoma Patients.

ICI therapy has greatly improved patient outcomes in melanoma, but at the cost of immune-related adverse events (irAEs). Data on the chronicity of irAEs, especially in real-world settings, are currently limited. We performed a retrospective chart review of 161 adult patients with melanoma treated with at least one cycle of ICI regimen in the adjuvant or metastatic setting: 129 patients received PD-1 inhibitor monotherapy and 32 received dual immunotherapy. Patients were grouped by duration of irAE: permanent (no complete resolution), long-term (resolution over a period ≥ 6 months), transient (resolution over a period < 6 months), or no irAEs. A total of 283 irAEs were reported in the whole patient population. Sixty-six (41.0%) patients developed permanent irAEs, fifteen (9.3%) experienced long-term irAEs as their longest-lasting toxicity, thirty-four (21.1%) developed transient irAEs only, and forty-six (28.6%) experienced no irAEs. Permanent irAEs occurred in 21 (65.6%) patients treated with dual immunotherapy and in 45 (34.9%) patients treated with monotherapy. The majority of permanent irAEs were endocrine-related (36.0%) or skin-related (32.4%). Grade 3–4 permanent irAEs occurred in 20 (12.4%) patients and included toxicities such as adrenal insufficiency, myocarditis, and myelitis. Fifty-three (32.9%) patients were still requiring treatment for long-term or permanent irAEs 6 months or more following the completion of ICI therapy, including twenty-four patients on thyroid hormone replacement and twenty-two on oral steroids. ICI treatment was temporarily interrupted for 64 (22.6%) irAEs and permanently discontinued due to irAEs in 38 patients (13.6% of irAEs, 23.6% of patients); additionally, 4 (2.5%) patients died of irAEs. Our findings show that ICI treatment in melanoma is associated with a wide range of toxicities that can be permanent and may have long-lasting impacts on patients, which should therefore be discussed when obtaining consent for treatment.

A Comprehensive Pan-Cancer Analysis of the Tumorigenic Effect of Leucine-Zipper-Like Transcription Regulator (LZTR1) in Human Cancer.

The elucidation of the action site, mechanism of Leucine-Zipper-like Transcription Regulator-1 (LZTR1) and its relationship with RAS-MAPK signaling pathway attracts more and more scholars to focus on the researches of LZTR1 and its role in tumorigenesis. However, there was no pan-cancer analysis between LZTR1 and human tumors reported before. Therefore, we are the first to investigate the potential oncogenic roles of LZTR1 across all tumor types based on the datasets of TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus). LZTR1 plays a double-edged role in tumor development and prognosis. We found that the high expression of LZTR1 brings better outcomes in esophageal carcinoma (ESCA) and head and neck squamous cell carcinoma (HNSC) but brings worth outcomes in uveal melanoma (UVM), adrenocortical carcinoma (ACC), liver hepatocellular carcinoma (LIHC), and prostate adenocarcinoma (PRAD). Moreover, the expression of LZTR1 also strongly associated with pathological in ACC and bladder urothelial carcinoma (BLCA). We also found that the LZTR1 expression was associated with some immune cell infiltration including endothelial cells, regulatory T cells (Tregs), T cell CD8+, natural killer cells (NK cell), macrophages, neutrophil granulocyte, and cancer-associated fibroblasts in different cancers. Missense mutation in LZTR1 was detected in most cancers from TCGA datasets. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Body (GO) method was used to explain the pathogenesis of LZTR1. Our pan-cancer study provides a relatively comprehensive understanding of the carcinogenic role of LZTR1 in human tumors.

Differences between Asian Americans and Pacific Islanders with cutaneous melanoma: A retrospective cohort analysis of 1339 cases

To the Editor: Many melanoma studies have analyzed Asians/Pacific Islanders (API) as 1 group rather than unique groups of Asian Americans (AAs) and Pacific Islanders (PIs). 1 Zheng Y.J. Ho C. Lazar A. Ortiz-Urda S. Poor melanoma outcomes and survival in Asian American and Pacific Islander patients. J Am Acad Dermatol. 2021; 84: 1725-1727https://doi.org/10.1016/j.jaad.2020.08.086 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar , 2 Qian Y. Johannet P. Sawyers A. Yu J. Osman I. Zhong J. The ongoing racial disparities in melanoma: an analysis of the surveillance, epidemiology, and end results database (1975-2016). J Am Acad Dermatol. 2021; 84: 1585-1593https://doi.org/10.1016/j.jaad.2020.08.097 Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar , 3 Shin S. Palis B.E. Phillips J.L. Stewart A.K. Perry R.R. Cutaneous melanoma in Asian-Americans. J Surg Oncol. 2009; 99: 114-118https://doi.org/10.1002/jso.21195 Crossref PubMed Scopus (23) Google Scholar Geographic origin and skin tone differ among races that comprise AA and PI. Little is known about differences between AA and PI with melanoma, which this study explores.

TRIP13/FLNA Complex Promotes Tumor Progression and Is Associated with Unfavorable Outcomes in Melanoma.

Cutaneous melanoma is a high-grade malignant tumor originating from skin melanocytes with high risk of recurrence and metastasis. Further study on the mechanism of melanoma development is urgently needed. Here, we performed a bioinformatic analysis to identify critical genes in melanoma using public datasets in the Gene Expression Omnibus database. Among these differentially expressed genes, thyroid hormone receptor interactor 13 (TRIP13) has been reported to exert an important role in the development of various tumors, while its role in melanoma remains unclear. We selected TRIP13 as a candidate gene for further study. TRIP13 expression in clinical specimens was evaluated by immunohistochemistry, and its association with patient prognosis was analyzed by the Kaplan-Meier method and log-rank test. MV3 and A2058 melanoma cells were transfected with lentiviral vector to overexpress or knockdown TRIP13 expression level, and then, its biological function was studied using a series of in vitro and in vivo assays. RNA sequencing, co-immunoprecipitation, and mass spectrometry were used to identify the underlying mechanism of TRIP13. The results of this study exhibited that TRIP13 expression was upregulated in melanoma tissue compared with normal tissues, and high levels of TRIP13 were closely correlated with poor prognoses of melanoma patients. Elevated TRIP13 promoted the invasion and migration of melanoma cells in vitro and enhanced lung metastasis in vivo, without an influence on tumor growth. Importantly, elevated TRIP13 promoted the epithelial-mesenchymal transition (EMT) of melanoma cells, indicating a higher metastatic potential of these cells. Mechanically, TRIP13 physically interacted with filamin A (FLNA) and then activated the PI3K/AKT pathway to transcriptional activation of EMT-related genes. The present study revealed that TRIP13 is a novel prognostic biomarker and potential therapeutic target for melanoma treatment.

Association of UV Radiation Exposure, Diagnostic Scrutiny, and Melanoma Incidence in US Counties

Although UV radiation exposure is the conventionally reported risk factor for cutaneous melanoma, an alternative exposure is diagnostic scrutiny: the more physicians look for and biopsy moles, the more melanoma they find. To assess the association of proxies for UV radiation exposure and diagnostic scrutiny with geographical patterns of melanoma incidence. This was a cross-sectional ecological analysis of the 727 continental US counties reporting to the Surveillance, Epidemiology, and End Results (SEER) Program (among a total of 3108 counties). Environmental data relevant to UV radiation exposure (from a variety of sources), Health Resources and Services Administration data relevant to diagnostic scrutiny, and SEER data on melanoma incidence among the non-Hispanic White population diagnosed with melanoma from 2012 through 2016 were combined. Data analysis was performed between January 2020 and July 2022. Three UV radiation proxies (UV daily dose, cloud variability, and temperature variability) and 3 diagnostic scrutiny proxies (median household income, dermatologists, and primary care physician supply). Melanoma incidence (in situ and invasive cancers). In total, 235 333 melanomas were diagnosed. Proxies for UV radiation exposure changed gradually across geography, while melanoma incidence and proxies for diagnostic scrutiny changed abruptly across contiguous counties. The UV daily dose, a variable the National Cancer Institute specifically developed for melanoma analyses, was uncorrelated with incidence (r = 0.03; P = .42). For context, smoking prevalence was highly correlated with lung cancer incidence in the same counties (r = 0.81; P < .001). Melanoma incidence was correlated with median household income (r = 0.43; P < .001). Counties with no dermatologists and shortages of primary care physicians had the lowest incidence, while counties amply supplied with both had the highest, despite having lower mean UV daily dose. There was little association between melanoma incidence and melanoma mortality (r = 0.09; P = .05), while the analogous association in lung cancer was strong (r = 0.96; P < .001). In this cross-sectional ecological study, the current geographical pattern of melanoma incidence across US counties was less associated with proxies for UV radiation exposure and more so with proxies for diagnostic scrutiny. Incidence-the fundamental epidemiologic measure of disease frequency-now had little association with the feared outcome of melanoma: death.