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Molecular Features of Skin Cancer
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Molecular Features of Skin Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (27 October 2022) | Viewed by 10621

Special Issue Editor

Dr. Rocco Cappellesso

E-Mail Website
Guest Editor
Pathological Anatomy Unit, University Hospital of Padua, Via Aristide Gabelli, 61, 35121 Padova, Italy
Interests: melanoma; skin cancer; merkel cell carcinoma; basal cell carcinoma; squamous cell carcinoma; molecular pathology; metastasis; sentinel lymph node; tumor cell plasticity

Special Issue Information

Dear Colleagues, 

Skin cancer is by far the most common type of cancer worldwide. The main types of skin cancer are melanoma, basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma. Most of these can be treated effectively if diagnosed early, but the prognosis can be poor in advanced disease. Molecular characterizations of these tumors and the understanding of the immune-escape mechanisms used by tumor cells have allowed us to create targeted or agnostic effective drugs. However, there is still the need for novel treatments, and thus, it is important to discover new molecular alterations or processes for their development. Recently, digital pathology has been shown to be able to identify molecular subgroups of cancers by analyzing the virtual slide with artificial intelligence systems.

The aim of this Special Issue is to provide studies and reviews offering insights into the molecular features of the different subtypes of skin cancers, analyzing the molecular pathways involved in tumor cell plasticity and in tumor progression and metastasis, and presenting digital pathology tools or methods to recognize molecular alterations in these tumors.

Dr. Rocco Cappellesso
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • skin cancer
  • melanoma
  • merkel cell carcinoma
  • squamous cell carcinoma
  • basal cell carcinoma
  • tumor cell plasticity
  • tumor progression
  • metastasis
  • molecular pathology
  • digital pathology

Published Papers (5 papers)

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Research

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15 pages, 4966 KiB  
Article
Comparative Expression Profiling Reveals Molecular Markers Involved in the Progression of Cutaneous Melanoma towards Metastasis
by Andreea D. Lazăr, Sorina Dinescu, Lea Sleiman, Adrian V. Dumitru, Mariana Costache and Marieta Costache
Int. J. Mol. Sci. 2023, 24(7), 6565; https://doi.org/10.3390/ijms24076565 - 31 Mar 2023
Viewed by 1529
Abstract
Cutaneous melanoma is one of the most aggressive types of cancer and often proves fatal in metastatic stages. Few treatment options are available, and its global incidence is quickly increasing. In order to gain an improved understanding of the molecular features regarding melanoma [...] Read more.
Cutaneous melanoma is one of the most aggressive types of cancer and often proves fatal in metastatic stages. Few treatment options are available, and its global incidence is quickly increasing. In order to gain an improved understanding of the molecular features regarding melanoma progression, we have compared gene and small non-coding RNA expression profiles from cell lines derived from primary melanoma (MelJuSo), lymph node metastasis (MNT-1) and brain metastasis (VMM1), representing distinct stages of malignant progression. Our preliminary results highlighted the aberrant regulation of molecular markers involved in several processes that aid melanoma progression and metastasis development, including extracellular matrix remodeling, migratory potential and angiogenesis. Moreover, bioinformatic analysis revealed potential targets of the microRNAs of interest. Confocal microscopy and immunohistochemistry analysis were used for validation at the protein level. Exploring the molecular landscape of melanoma may contribute to the achievement of future efficient targeted therapy, as well as better prevention, diagnosis and clinical management. Full article
(This article belongs to the Special Issue Molecular Features of Skin Cancer)
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16 pages, 1916 KiB  
Article
Imaging Mass Spectrometry for the Classification of Melanoma Based on BRAF/NRAS Mutational Status
by Rita Casadonte, Mark Kriegsmann, Katharina Kriegsmann, Helene Streit, Rolf Rüdiger Meliß, Cornelia S. L. Müller and Joerg Kriegsmann
Int. J. Mol. Sci. 2023, 24(6), 5110; https://doi.org/10.3390/ijms24065110 - 7 Mar 2023
Cited by 1 | Viewed by 1749
Abstract
Mutations of the oncogenes v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and neuroblastoma RAS viral oncogene homolog (NRAS) are the most frequent genetic alterations in melanoma and are mutually exclusive. BRAF V600 mutations are predictive for response to [...] Read more.
Mutations of the oncogenes v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and neuroblastoma RAS viral oncogene homolog (NRAS) are the most frequent genetic alterations in melanoma and are mutually exclusive. BRAF V600 mutations are predictive for response to the two BRAF inhibitors vemurafenib and dabrafenib and the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib. However, inter- and intra-tumoral heterogeneity and the development of acquired resistance to BRAF inhibitors have important clinical implications. Here, we investigated and compared the molecular profile of BRAF and NRAS mutated and wildtype melanoma patients’ tissue samples using imaging mass spectrometry-based proteomic technology, to identify specific molecular signatures associated with the respective tumors. SCiLSLab and R-statistical software were used to classify peptide profiles using linear discriminant analysis and support vector machine models optimized with two internal cross-validation methods (leave-one-out, k-fold). Classification models showed molecular differences between BRAF and NRAS mutated melanoma, and identification of both was possible with an accuracy of 87–89% and 76–79%, depending on the respective classification method applied. In addition, differential expression of some predictive proteins, such as histones or glyceraldehyde-3-phosphate-dehydrogenase, correlated with BRAF or NRAS mutation status. Overall, these findings provide a new molecular method to classify melanoma patients carrying BRAF and NRAS mutations and help provide a broader view of the molecular characteristics of these patients that may help understand the signaling pathways and interactions involving the altered genes. Full article
(This article belongs to the Special Issue Molecular Features of Skin Cancer)
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11 pages, 4171 KiB  
Article
TRK Protein Expression in Merkel Cell Carcinoma Is Not Caused by NTRK Fusions
by Rocco Cappellesso, Lorenzo Nicolè, Paolo Del Fiore, Luisa Barzon, Alessandro Sinigaglia, Silvia Riccetti, Renato Franco, Federica Zito Marino, Giada Munari, Carolina Zamuner, Francesco Cavallin, Marta Sbaraglia, Francesca Galuppini, Franco Bassetto, Mauro Alaibac, Vanna Chiarion-Sileni, Luisa Piccin, Clara Benna, Matteo Fassan, Simone Mocellin and Angelo Paolo Dei Tosadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2022, 23(23), 15366; https://doi.org/10.3390/ijms232315366 - 6 Dec 2022
Cited by 1 | Viewed by 1538
Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignant tumor with neuroendocrine differentiation, with a rapidly growing incidence rate, high risk of recurrence, and aggressive behavior. The available therapeutic options for advanced disease are limited and there is a pressing need [...] Read more.
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignant tumor with neuroendocrine differentiation, with a rapidly growing incidence rate, high risk of recurrence, and aggressive behavior. The available therapeutic options for advanced disease are limited and there is a pressing need for new treatments. Tumors harboring fusions involving one of the neurotrophin receptor tyrosine kinase (NTRK) genes are now actionable with targeted inhibitors. NTRK-fused genes have been identified in neuroendocrine tumors of other sites; thus, a series of 76 MCCs were firstly analyzed with pan-TRK immunohistochemistry and the positive ones with real-time RT-PCR, RNA-based NGS, and FISH to detect the eventual underlying gene fusion. Despite 34 MCCs showing pan-TRK expression, NTRK fusions were not found in any cases. As in other tumors with neural differentiation, TRK expression seems to be physiological and not caused by gene fusions. Full article
(This article belongs to the Special Issue Molecular Features of Skin Cancer)
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14 pages, 3463 KiB  
Article
Increased Expression of Flightless I in Cutaneous Squamous Cell Carcinoma Affects Wnt/β-Catenin Signaling Pathway
by Gink N. Yang, Xanthe L. Strudwick, Claudine S. Bonder, Zlatko Kopecki and Allison J. Cowin
Int. J. Mol. Sci. 2021, 22(24), 13203; https://doi.org/10.3390/ijms222413203 - 8 Dec 2021
Viewed by 2263
Abstract
Cutaneous squamous cell carcinoma (cSCC) accounts for 25% of cutaneous malignancies diagnosed in Caucasian populations. Surgical removal in combination with radiation and chemotherapy are effective treatments for cSCC. Nevertheless, the aggressive metastatic forms of cSCC still have a relatively poor patient outcome. Studies [...] Read more.
Cutaneous squamous cell carcinoma (cSCC) accounts for 25% of cutaneous malignancies diagnosed in Caucasian populations. Surgical removal in combination with radiation and chemotherapy are effective treatments for cSCC. Nevertheless, the aggressive metastatic forms of cSCC still have a relatively poor patient outcome. Studies have linked actin cytoskeletal dynamics and the Wnt/β-catenin signaling pathway as important modulators of cSCC pathogenesis. Previous studies have also shown that the actin-remodeling protein Flightless (Flii) is a negative regulator of cSCC. The aim of this study was to investigate if the functional effects of Flii on cSCC involve the Wnt/β-catenin signaling pathway. Flii knockdown was performed using siRNA in a human late stage aggressive metastatic cSCC cell line (MET-1) alongside analysis of Flii genetic murine models of 3-methylcholanthrene induced cSCC. Flii was increased in a MET-1 cSCC cell line and reducing Flii expression led to fewer PCNA positive cells and a concomitant reduction in cellular proliferation and symmetrical division. Knockdown of Flii led to decreased β-catenin and a decrease in the expression of the downstream effector of β-catenin signaling protein SOX9. 3-Methylcholanthrene (MCA)-induced cSCC in Flii overexpressing mice showed increased markers of cancer metastasis including talin and keratin-14 and a significant increase in SOX9 alongside a reduction in Flii associated protein (Flap-1). Taken together, this study demonstrates a role for Flii in regulating proteins involved in cSCC proliferation and tumor progression and suggests a potential role for Flii in aggressive metastatic cSCC. Full article
(This article belongs to the Special Issue Molecular Features of Skin Cancer)
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Review

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22 pages, 1607 KiB  
Review
Skin Cancer Metabolic Profile Assessed by Different Analytical Platforms
by Yousra A. Hagyousif, Basma M. Sharaf, Ruba A. Zenati, Waseem El-Huneidi, Yasser Bustanji, Eman Abu-Gharbieh, Mohammad A. Y. Alqudah, Alexander D. Giddey, Ahmad Y. Abuhelwa, Karem H. Alzoubi, Nelson C. Soares and Mohammad H. Semreen
Int. J. Mol. Sci. 2023, 24(2), 1604; https://doi.org/10.3390/ijms24021604 - 13 Jan 2023
Cited by 5 | Viewed by 2752
Abstract
Skin cancer, including malignant melanoma (MM) and keratinocyte carcinoma (KC), historically named non-melanoma skin cancers (NMSC), represents the most common type of cancer among the white skin population. Despite decades of clinical research, the incidence rate of melanoma is increasing globally. Therefore, a [...] Read more.
Skin cancer, including malignant melanoma (MM) and keratinocyte carcinoma (KC), historically named non-melanoma skin cancers (NMSC), represents the most common type of cancer among the white skin population. Despite decades of clinical research, the incidence rate of melanoma is increasing globally. Therefore, a better understanding of disease pathogenesis and resistance mechanisms is considered vital to accomplish early diagnosis and satisfactory control. The “Omics” field has recently gained attention, as it can help in identifying and exploring metabolites and metabolic pathways that assist cancer cells in proliferation, which can be further utilized to improve the diagnosis and treatment of skin cancer. Although skin tissues contain diverse metabolic enzymes, it remains challenging to fully characterize these metabolites. Metabolomics is a powerful omics technique that allows us to measure and compare a vast array of metabolites in a biological sample. This technology enables us to study the dermal metabolic effects and get a clear explanation of the pathogenesis of skin diseases. The purpose of this literature review is to illustrate how metabolomics technology can be used to evaluate the metabolic profile of human skin cancer, using a variety of analytical platforms including gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). Data collection has not been based on any analytical method. Full article
(This article belongs to the Special Issue Molecular Features of Skin Cancer)
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