Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer
Abstract
:1. Introduction
2. Etiology
2.1. Ultraviolet (UV) Light
2.2. Genetic Background
2.3. Infectious Agents
3. Current Molecular Biomarkers for NMSC
3.1. Telomere Length (TL)
3.2. Telomerase Activity (TA)
3.3. Epigenetic Modifications
3.3.1. CpG Island Methylation (CIM)
3.3.2. Histone Methylation and Acetylation
3.3.3. MicroRNAs (miRNAs or miRs)
4. Biomarkers under Evaluation
Micronuclei Frequency (MNf)
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
NMSC | non-melanoma skin cancer |
BCC | basal cell carcinoma |
SCC | squamous cell carcinoma |
MCC | Merkel cell carcinoma |
BD | Bowen’s Disease |
AK | Actinic Keratosis |
UV | Ultraviolet |
β-HPV | β-Human papilloma virus |
UVB | ultraviolet B |
UVA | Ultraviolet A |
EGFR | epidermal growth factor receptor |
FGFR | fibroblast growth factor receptors |
EBV | Epstein–Barr virus |
MCPyV | Merkel Cell Polyomavirus |
LTAg | large T-antigen |
STAg | small t-antigen |
TL | Telomere length |
hTERT | human telomerase reverse transcriptase |
hTR | human telomere RNA |
TERC | telomerase RNA component |
TA | telomerase activity |
PBL | peripheral blood lymphocytes |
CIM | CpG island methylation |
DNMTs | DNA methyltransferases |
LAD | lamina-associated domains |
HATs | acetyltransferases |
HDACs | histone deacetyltransferases |
pri-miRNAs | primary miRNAs |
pre-miRNAs | precursor miRNAs |
3′ UTR | 3′-untranslated region |
5′ UTR | 5′-untranslated region |
MN | Micronuclei |
MNf | Micronuclei frequency |
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Gene Target | Methylation Status | Type of NMSC | Cellular Effect | Reference |
---|---|---|---|---|
CDKN2A | Hypermethylated | SCC | Cell cycle deregulation | Brown et al. [102] |
CDH1 | Hypermethylated | SCC | Cellular environment deregulation | Chiles et al. [103] Murao et al. [104] |
CDH13 | Hypermethylated | SCC | Cellular environment deregulation | Takeuchi et al. [105] |
FOXE1 | Hypermethylated | SCC | Modulator of Wnt signaling | Venza et al. [106] |
SFRPs | Hypermethylated | SCC | Modulator of Wnt signaling | Liang et al. [107] |
FRZB | Hypermethylated | SCC | Modulator of Wnt signaling | Darr et al. [108] |
ASC | Hypermethylated | SCC | Deregulation of apoptosis | Meier et al. [109] |
G0S2 | Hypermethylated | SCC | Deregulation of apoptosis | Nobeyama et al. [110] |
DAPK1 | Hypermethylated | SCC | Deregulation of apoptosis | Li et al. [111] |
miRNA-204 | Hypermethylated | SCC | Deregulation of apoptosis | Toll et al. [112] |
DSS1 | Hypomethylation | SCC | Deregulated post-translational protein modification | Venza et al. [113] |
Global DNA | Hypomethylation | SCC (benign) | Restricted genomic silencing | Hervás-Marín et al. [101] |
Global DNA | Hypermethylation | SCC (aggressive) | Extensive genomic silencing | |
FHIT promoter | Hypomethylated | BCC | Replication stress and DNA damage | Goldberg et al. [114] |
PTCH promoter | Hypermethylated | BCC (small number of cases) | Deactivation of tumor suppressor genes | Heitzer et al. [115] |
MYCL2 | Hypomethylated | BCC (metastatic) | Activation of proto-oncogene | Darr et al. [108] |
p14-ARK | Hypermethylated | MCC | Deactivation of tumor suppressor genes | Greenberg et al. [116] |
DUSP2, CDKN2A promoter | Hypermethylated | MCC | Deactivation of tumor suppressor genes | Harms et al. [117] |
miRNA | Expression Status | Type of NMSC | Possible Significance | Reference |
---|---|---|---|---|
hsa-miR-223-3p, | Upregulated | BCC | Diagnosis | Sand et al. [145] |
hsa-miR-197-3p, | ||||
hsa-miR-342-3p, | ||||
hsa-miR-505-3p, | ||||
hsa-miR-204-5p, | ||||
hsa-miR-941, | ||||
hsa-miR-145-5p, | ||||
hsa-miR-301b-3p, | ||||
hsa-miR-452-5p, | ||||
hsa-miR-191-5p, | ||||
miR203 | Downregulated | BCC | Diagnosis, Therapy | Yi et al. [146] |
miR-34a | Downregulated | BCC | Prognosis | Hu et al. [149] |
miR-21, | Upregulated | SCC | Diagnosis | Mizrahi et al. [150], Yu et al. [151] |
miR-205, | ||||
miR-365, | ||||
miR-31, | ||||
miR-135b, | ||||
miR-424, | ||||
miR-320, | ||||
miR-222 | ||||
miR-15a, | ||||
miR-142 | ||||
miR-186 | ||||
miR-20a, | Downregulated | SCC | Diagnosis | García-Sancha et al. [152] |
miR-203, | ||||
miR-181a, miR-125b, miR-34a, | ||||
miR-148a, miR-214, | ||||
miR-124, | ||||
miR-204, | ||||
miR-199a | ||||
miR-205 | Upregulated | SCC | Diagnosis, Prognosis | Cañueto et al. [153], Stojadinovic et al. [154] |
miR-221 | Upregulated | SCC | Diagnosis, therapy | Gong et al. [155] |
miR-203 | varied | SCC | Prognosis | Cañueto et al. [153] |
miR-20a | Varied | SCC | Prognosis | Zhang et al. [156] |
miR-502-3p, | Upregulated | MCC | Diagnosis | Ning et al. [157] |
miR-9, | ||||
miR-7, | ||||
miR-340 | ||||
miR-182, | ||||
miR-190b, | ||||
miR-873, | ||||
miR-183 | ||||
miR-3170, | Downregulated | |||
miR-125b, | ||||
miR-374c | ||||
miR-182, | Downregulated in MCPyV-negative cell line | |||
miR-183, | ||||
miR-190b, | ||||
miR-340 | ||||
miR-30a | Upregulated | MCPyV-positive MCCs | Diagnosis | Veija et al. [158] |
miR-190b, | ||||
miR-142-3p, | ||||
miR-1539 | ||||
miR-181d | MCPyV-negative MCCs | |||
miR-375 | Upregulated | MCC | Diagnosis | Renwick et al. [159] |
miR-30a, | Upregulated | MCC | Diagnosis | Moens group [160] |
miR-125b, | ||||
miR-183, | ||||
miR-190b | ||||
miR-375 |
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Nikolouzakis, T.K.; Falzone, L.; Lasithiotakis, K.; Krüger-Krasagakis, S.; Kalogeraki, A.; Sifaki, M.; Spandidos, D.A.; Chrysos, E.; Tsatsakis, A.; Tsiaoussis, J. Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer. J. Clin. Med. 2020, 9, 2868. https://doi.org/10.3390/jcm9092868
Nikolouzakis TK, Falzone L, Lasithiotakis K, Krüger-Krasagakis S, Kalogeraki A, Sifaki M, Spandidos DA, Chrysos E, Tsatsakis A, Tsiaoussis J. Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer. Journal of Clinical Medicine. 2020; 9(9):2868. https://doi.org/10.3390/jcm9092868
Chicago/Turabian StyleNikolouzakis, Taxiarchis Konstantinos, Luca Falzone, Konstantinos Lasithiotakis, Sabine Krüger-Krasagakis, Alexandra Kalogeraki, Maria Sifaki, Demetrios A. Spandidos, Emmanuel Chrysos, Aristidis Tsatsakis, and John Tsiaoussis. 2020. "Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer" Journal of Clinical Medicine 9, no. 9: 2868. https://doi.org/10.3390/jcm9092868