Current state of melanoma diagnosis and treatment

Davis, Lauren Evoy; Shalin, Sara C.; Tackett, Alan J.

doi:10.1080/15384047.2019.1640032

Cited by 593 publications

(564 citation statements)

References 117 publications

(286 reference statements)

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“…The most important prognostic factor of melanoma is the BRAF mutational status [6]. The other prognostic factors are American Joint Committee on Cancer (AJCC) melanoma TNM (tumor, node, metastasis) staging [7], Clark level, and Breslow thickness [8], and they are useful for the clinical management of patients with melanoma. In the United States, patients present melanoma at different stages, with 84% of them presenting localized disease, 9% presenting regional disease, and 4% exhibiting distant metastasis [9].…”

Section: Introductionmentioning

confidence: 99%

A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients

Yang

Shui

et al. 2020

Cancer Cell Int

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Background: Programmed death-ligand 1 (PD-L1) was the first identified ligand of programmed death-1 (PD-1). PD-1/PD-L1 interactions inhibit T cell-mediated immune responses, limit cytokine production, and promote tumor immune escape. Recently, many studies have investigated the prognostic value of PD-L1 expression in patients with melanoma. However, the results of these analyses remain a subject of debate. We have therefore carried out a metaanalysis to identify the prognostic role of PD-L1 in melanoma. Methods: A thorough medical literature search was performed in the databases PubMed, Web of Science, and Embase until October 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate the correlation between PD-L1 overexpression and prognosis. Publication bias was evaluated using Begg's test and Egger's test. Results: Thirteen articles with 1062 enrolled patients were included in this meta-analysis. High PD-L1 expression did not correlate with overall survival (OS) (HR = 0.93, 95% CI 0.57-1.52, P = 0.781) or progression-free survival (PFS) (HR = 0.82, 95% CI 0.43-1.54, P = 0.535). However, PD-L1 overexpression correlated with the absence of lymph node (LN) metastasis (OR = 0.46, 95% CI 0.22-0.95, P = 0.036). Further, there was no significant relationship between PD-L1 expression and sex (OR = 1.29, 95% CI 0.90-1.84, P = 0.159), age (OR = 0.90, 95% CI 0.51-1.57, P = 0.708), or Eastern Cooperative Oncology Group Performance Status (OR = 0.55, 95% CI 0.06-4.83, P = 0.592). Conclusions: This meta-analysis suggested that PD-L1 expression did not predict an inferior prognosis in patients with melanoma. However, high PD-L1 expression was associated with absence of LN metastasis in such patients.

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Section: Introductionmentioning

confidence: 99%

A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients

Yang

Shui

et al. 2020

Cancer Cell Int

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“…PFS and MSS were calculated using Kaplan–Meier estimates, and differences between survival curves were analyzed by log-rank test 25 . The impact of age at diagnosis, gender, tumor location, Breslow thickness 37 , Clark level, TNM stage and genotypes of each analyzed SNV in survival of patients were evaluated using univariate Cox proportional hazards ratio (HR) regression. At a second time, all variables with p < 0.20 were included in the multivariate Cox regression.…”

Section: Methodsmentioning

confidence: 99%

Inherited variations in human pigmentation-related genes modulate cutaneous melanoma risk and clinicopathological features in Brazilian population

Lourenço

Oliveira

Carvalho

et al. 2020

Sci Rep

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Ultraviolet light exposure and cutaneous pigmentation are important host risk factors for cutaneous melanoma (CM), and it is well known that inherited ability to produce melanin varies in humans. The study aimed to identify single-nucleotide variants (SNVs) on pigmentation-related genes with importance in risk and clinicopathological aspects of CM. The study was conducted in two stages. In stage 1, 103 CM patients and 103 controls were analyzed using Genome-Wide Human SNV Arrays in order to identify SNVs in pigmentation-related genes, and the most important SNVs were selected for data validation in stage 2 by real-time polymerase-chain reaction in 247 CM patients and 280 controls. ADCY3 c.675+9196T>G, CREB1 c.303+373G>A, and MITF c.938-325G>A were selected for data validation among 74 SNVs. Individuals with CREB1 GA or AA genotype and allele “A” were under 1.79 and 1.47-fold increased risks of CM than others, respectively. Excesses of CREB1 AA and MITF AA genotype were seen in patients with tumors at Clark levels III to V (27.8% versus 13.7%) and at III or IV stages (46.1% versus 24.9%) compared to others, respectively. When compared to others, patients with ADCY3 TT had 1.89 more chances of presenting CM progression, and those with MITF GA or AA had 2.20 more chances of evolving to death by CM. Our data provide, for the first time, preliminary evidence that inherited abnormalities in ADCY3 , CREB1 , and MITF pigmentation-related genes, not only can increase the risk to CM, but also influence CM patients’ clinicopathological features.

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“…In addition to external causes such as ultraviolet radiation, familial genetic factors cannot be ignored. Patients with melanoma diagnosed early and treated surgically had a higher survival rate; however, those with advanced metastatic melanoma had lower survival rates [1] . In recent years, the treatment of melanoma has included conventional chemotherapy and radiation therapy, as well as therapies targeting B-Raf proto-oncogene, serine/threonine kinase (BRAF) and MAP kinase-ERK kinase (MEK).…”

Section: Introductionmentioning

confidence: 96%

Identification of Co-Expressed Genes Promoting CD8+ T Cell Infiltration in Melanoma Tumor Microenvironments

Yan

Wang

Xiao

2020

Preprint

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Purpose: To identify CD8+ T cell-related factors and the co-expression network in melanoma, to illustrate the interactions among CD8+ T cell-related genes in the melanoma tumor microenvironment.Method: We obtained melanoma and para-carcinoma tissue mRNA matrices from TCGA-SKCM and GSE65904. The CIBERSORT algorithm was used to assess CD8+ T cell proportions and the “estimate” package was used to assess melanoma tumor microenvironment purity. Weighted gene co-expression network analysis was used to identify the most related co-expression modules in TCGA-SKCM and GSE65904. Subsequently, a co-expression network was built based on the common results in the two cohorts. Results: Nine co-expressed genes (CCL5, GAP5, GZMA, GZMH, IRF1, LAG3, PRF1, NKG7, PSMB10) were identified as CD8+ T cell-related genes that promoted infiltration of CD8+ T cells, which were enriched in the cellular response to interferon−gamma process and antigen processing and presentation of peptide antigen. In the low expression level group, inflammation and immune responses were weaker, and the tumor purity was higher, suggesting that these genes were immune protective factors that improved the prognosis of melanoma. Besides this, co-expression factors negatively correlated with angiogenesis factors and positively correlated with angiogenesis inhibitors. Conclusion: These nine co-expressed genes promote high levels of infiltration of CD8+ T cells by the cellular response to the interferon−gamma process. The mechanism might provide new pathways for treatment of patients who are insensitive to PD-1 immunotherapy due to low degrees of CD8+ T cell infiltration.

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Current state of melanoma diagnosis and treatment

Cited by 593 publications

References 117 publications

A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients

A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients

Inherited variations in human pigmentation-related genes modulate cutaneous melanoma risk and clinicopathological features in Brazilian population

Identification of Co-Expressed Genes Promoting CD8+ T Cell Infiltration in Melanoma Tumor Microenvironments

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