Behind the Scene: Exploiting MC1R in Skin Cancer Risk and Prevention

Manganelli, Michele; Guida, Stefania; Ferretta, Anna; Pellacani, Giovanni; Porcelli, Letizia; Azzariti, Amalia; Guida, Gabriella

doi:10.3390/genes12071093

Cited by 17 publications

(15 citation statements)

References 221 publications

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“…The latest research indicates that SLC44A4 may be a potential target for the diagnosis, prognosis, and treatment of clear cell renal cell carcinoma ( 31 ). MC1R has been relevant to an increased susceptibility to skin cancer ( 32 ). In addition, MC1R antagonists and agonists might be employed as potential therapeutic drugs for skin cancer ( 33 , 34 ).…”

Section: Discussionmentioning

confidence: 99%

An Intratumor Heterogeneity-Related Signature for Predicting Prognosis, Immune Landscape, and Chemotherapy Response in Colon Adenocarcinoma

Liu

Wang

et al. 2022

Front. Med.

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BackgroundColon adenocarcinoma (COAD) is a frequent malignancy of the digestive system with a poor prognosis and high mortality rate worldwide. Intratumor heterogeneity (ITH) is associated with tumor progression, poor prognosis, immunosuppression, and therapy resistance. However, the relationship between ITH and prognosis, the immune microenvironment, and the chemotherapy response in COAD patients remains unknown, and this knowledge is urgently needed.MethodsWe obtained clinical information and gene expression data for COAD patients from The Cancer Genome Atlas (TCGA) database. The DEPTH2 algorithm was utilized to evaluate the ITH score. X-tile software was used to determine the optimal cutoff value of the ITH score. The COAD patients were divided into high- and low-ITH groups based on the cutoff value. We analyzed prognosis, tumor mutation burden (TMB), gene mutations, and immune checkpoint expression between the high- and low-ITH groups. Differentially expressed genes (DEGs) in the high- and low-ITH groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. We performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to screen the prognosis-related genes for the construction of an ITH-related prognostic signature. The nomogram was used to predict the overall survival (OS) of COAD patients. The protein–protein interaction (PPI) network was constructed by using the GeneMANIA database. Principal component analysis (PCA) and single-sample gene set enrichment analysis (ssGSEA) were employed to explore the differences in biological pathway activation status between the high- and low-risk groups. The proportion and type of tumor-infiltrating immune cells were evaluated by the CIBERSORT and ESTIMATE algorithms. Additionally, we assessed the chemotherapy response and predicted small-molecule drugs for treatment. Finally, the expression of the prognosis-related genes was validated by using the UALCAN database and Human Protein Atlas (HPA) database.ResultsThe OS of the high-ITH group was worse than that of the low-ITH group. A positive correlation between ITH and TMB was identified. In subgroups stratified by age, gender, and tumor stage, the OS of the low-ITH group remained better than that of the high-ITH group. There were dramatic differences in the mutated genes, single nucleotide variant classes, variant types, immune checkpoints and cooccurring and mutually exclusive mutations of the DEGs between the high- and low-ITH groups. Based on the DEGs between the high- and low-ITH groups, we constructed a five-gene signature consisting of CEACAM5, ENO2, GABBR1, MC1R, and SLC44A4. The COAD patients were divided into high- and low-risk groups according to the median risk score. The OS of the high-risk group was worse than that of the low-risk group. The nomogram was used to accurately predict the 1-, 3- and 5-year OS of COAD patients and showed good calibration and moderate discrimination ability. The stromal score, immune score, and ESTIMATE score of the high-risk group were significantly higher than those of the low-risk group, whereas tumor purity showed the opposite trend. The patients classified by the risk score had distinguishable sensitivity to chemotherapeutic drugs. Finally, two public databases confirmed that CEACAM5 and SLC44A4 were upregulated in normal tissues compared with COAD tissues, and ENO2, GABBR1, and MC1R were upregulated in COAD tissues compared with normal tissues.ConclusionOverall, we identified an ITH-related prognostic signature for COAD that was closely related to the tumor microenvironment and chemotherapy response. This signature may help clinicians make more personalized and precise treatment decisions for COAD patients.

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Section: Discussionmentioning

confidence: 99%

An Intratumor Heterogeneity-Related Signature for Predicting Prognosis, Immune Landscape, and Chemotherapy Response in Colon Adenocarcinoma

Liu

Wang

et al. 2022

Front. Med.

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“…α-MSH is secreted from keratinocytes and binds to the melanocortin 1 receptor (MC1R) in melanocytes, which is a G-protein coupled receptor that induces the synthesis of melanin in response to UVR damage initially detected by keratinocytes ( Figure 1 B) [ 36 , 37 , 38 ]. In parallel to switching on eumelanin (dark melanin) production and driving the tanning response, activation of MC1R also activates DNA damage repair [ 36 , 39 , 40 , 41 ].…”

Section: Melanomamentioning

confidence: 99%

3D Bioprinting: An Enabling Technology to Understand Melanoma

Fernandes

Vyas

Lim

et al. 2022

Cancers

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Melanoma is a potentially fatal cancer with rising incidence over the last 50 years, associated with enhanced sun exposure and ultraviolet radiation. Its incidence is highest in people of European descent and the ageing population. There are multiple clinical and epidemiological variables affecting melanoma incidence and mortality, such as sex, ethnicity, UV exposure, anatomic site, and age. Although survival has improved in recent years due to advances in targeted and immunotherapies, new understanding of melanoma biology and disease progression is vital to improving clinical outcomes. Efforts to develop three-dimensional human skin equivalent models using biofabrication techniques, such as bioprinting, promise to deliver a better understanding of the complexity of melanoma and associated risk factors. These 3D skin models can be used as a platform for patient specific models and testing therapeutics.

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“…Differences in the distribution and type of melanin produced in cutaneous melanocytes regulate wide variations of human hair and skin colors [ 79 , 80 , 81 ]. Melanin consists of two distinct types: one is the brown/black eumelanin, which is photoprotective.…”

Section: Molecular Mechanismsmentioning

confidence: 99%

“…It is then possible that the same effect occurs in the carcinogenesis of BCCs. BCC risk in the two or more MC1R variants is reported to be increasing independently of skin type [ 81 , 85 , 87 , 88 , 89 , 90 , 91 ]. Interestingly, the frequency of P1315L mutation in BCCs is not associated with the MC1R genotype [ 89 ].…”

Section: Molecular Mechanismsmentioning

confidence: 99%

Molecular Mechanisms and Targeted Therapies of Advanced Basal Cell Carcinoma

Hoashi

Kanda

Saeki

2022

IJMS

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Among human cutaneous malignancies, basal cell carcinoma is the most common. Solid advances in unveiling the molecular mechanisms of basal cell carcinoma have emerged in recent years. In Gorlin syndrome, which shows basal cell carcinoma predisposition, identification of the patched 1 gene (PTCH1) mutation was a dramatic breakthrough in understanding the carcinogenesis of basal cell carcinoma. PTCH1 plays a role in the hedgehog pathway, and dysregulations of this pathway are known to be crucial for the carcinogenesis of many types of cancers including sporadic as well as hereditary basal cell carcinoma. In this review, we summarize the clinical features, pathological features and hedgehog pathway as applied in basal cell carcinoma. Other crucial molecules, such as p53 and melanocortin-1 receptor are also discussed. Due to recent advances, therapeutic strategies based on the precise molecular mechanisms of basal cell carcinoma are emerging. Target therapies and biomarkers are also discussed.

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Behind the Scene: Exploiting MC1R in Skin Cancer Risk and Prevention

Cited by 17 publications

References 221 publications

An Intratumor Heterogeneity-Related Signature for Predicting Prognosis, Immune Landscape, and Chemotherapy Response in Colon Adenocarcinoma

An Intratumor Heterogeneity-Related Signature for Predicting Prognosis, Immune Landscape, and Chemotherapy Response in Colon Adenocarcinoma

3D Bioprinting: An Enabling Technology to Understand Melanoma

Molecular Mechanisms and Targeted Therapies of Advanced Basal Cell Carcinoma

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