Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas
Abstract
:1. Introduction
2. Results
2.1. Analysis of Clinicopathological Predictors in Thick CM
2.2. Demographic and Clinicopathological Characteristics of the Study Population for the Molecular Analysis
2.3. Molecular Analysis
2.3.1. Differentially Expressed Genes in Thick CM
2.3.2. Pathway Analysis: TNF-like Weak Inducer of Apoptosis (TWEAK) Pathway
2.3.3. Validation in the Leeds Dataset
3. Discussion
4. Materials and Methods
4.1. Patient Populations
4.2. Tumor Tissue Samples: RNA Extraction and Purification
4.3. Construction of RNA-Seq Library and Sequencing
4.4. Bioinformatics Analysis
4.5. Validation Using the Leeds Dataset
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AJCC | American Joint Committee on Cancer |
AKT | AKT Serine/Threonine Kinase |
AL | acrolentiginous melanoma |
ARID2 | AT-Rich Interaction Domain 2 |
BIRC2 | Baculoviral IAP Repeat Containing 2 |
BRAF | B-Raf Proto-Oncogene, Serine/Threonine Kinase |
CASP7 | Caspase 7 |
CASP8 | Caspase 8 |
CCND1 | Cyclin D1 |
CDK4 | Cyclin Dependent Kinase 4 |
CDKN2a | Cyclin Dependent Kinase Inhibitor 2A |
cIAP1 | Cellular Inhibitor of Apoptosis 1 |
CM | Cutaneous melanoma |
DEG | differential expressed genes |
FADD | Fas Associated Via Death Domain |
Fn14 | Fibroblast growth factor-inducible 14 |
FFPE | Formalin-Fixed Paraffin-Embedded |
GSTP1 | Glutathione S-Transferase P |
H & E | hematoxylin & eosin |
HLA-DQA1 | Major Histocompatibility Complex, Class II, DQ Alpha 1 |
IGHM | Immunoglobulin Heavy Constant Mu |
IL6 | interleukin 6 |
JNK | c-Jun N-terminal kinase |
M− | non-metastatic CMs |
M+ | metastatic CMs |
MAP | Mitogen-Activated Protein |
MAP3K14 | Mitogen-Activated Protein Kinase Kinase Kinase 14 |
MDM2 | MDM2 Proto-Oncogene |
MET | MET Proto-Oncogene, Receptor Tyrosine Kinase |
MET, c-MET | Mesenchymal-epithelial transition tyrosine kinase receptor |
MMP9 | expression of matrix metalloproteinase 9 |
NIK | NFkB Inducing Kinase |
NM | Nodular melanoma |
NRAS | NRAS Proto-Oncogene, GTPase |
NSCLC | Non-small-cell lung carcinoma |
OG | oncogene |
P53 | Tumor Protein P53 |
PTEN | Phosphatase And Tensin Homolog |
RAMP1 | Receptor Activity Modifying Protein 1 |
Ras/MAPK | Ras/Mitogen-Activated Protein Kinase |
RIPK1 | Receptor Interacting Serine/Threonine Kinase 1 |
RNA | ribonucleic acid |
SH3GL2 | SH3 Domain Containing GRB2 Like 2, Endophilin A1 |
SSM | Superficial spreading melanoma |
STK19 | Serine/Threonine Kinase 19 |
TMOD1 | Tropomodulin 1 |
TNF | tumor necrose factor |
TNF-alpha | Tumor Necrosis Factor-alpha |
TNFR | tumor necrose factor receptor |
TNFR1 | Tumor Necrosis Factor Receptor Type 1 |
TRAF | TNF Receptor Associated Factor |
TRIM63 | Tripartite Motif Containing 63 |
TSG | tumor suppressor gene |
TWEAK | TNF-like weak inducer of apoptosis |
TWIST2 | Twist Family BHLH Transcription Factor 2 |
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Characteristics | Frequency (n) | Percent (%) | |
---|---|---|---|
Metastasis | No | 12 | 50 |
Yes | 12 | 50 | |
Subtype | SSM | 4 | 16.7 |
NM | 13 | 54.2 | |
AL | 7 | 29.2 | |
Gender | Female | 6 | 25 |
Male | 18 | 75 | |
Ulceration | No | 8 | 33.3 |
Yes | 16 | 66.7 | |
Mitosis | No | 4 | 16.7 |
Yes | 20 | 83.3 | |
Age | 40–59 y | 8 | 33.3 |
≥60 y | 16 | 66.7 | |
Site | Extremity | 11 | 45.8 |
Trunk | 6 | 25 | |
Head and neck | 7 | 29.2 | |
Breslow thickness | 2–4 mm | 12 | 50 |
>4 mm | 12 | 50 |
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Güvenç, C.; Antoranz, A.; Szumera-Ciećkiewicz, A.; Teterycz, P.P.; Rutkowski, P.R.; Rawson, R.V.; Scolyer, R.A.; Thompson, J.F.; Newton-Bishop, J.; Stas, M.; et al. Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas. Int. J. Mol. Sci. 2021, 22, 10568. https://doi.org/10.3390/ijms221910568
Güvenç C, Antoranz A, Szumera-Ciećkiewicz A, Teterycz PP, Rutkowski PR, Rawson RV, Scolyer RA, Thompson JF, Newton-Bishop J, Stas M, et al. Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas. International Journal of Molecular Sciences. 2021; 22(19):10568. https://doi.org/10.3390/ijms221910568
Chicago/Turabian StyleGüvenç, Canan, Asier Antoranz, Anna Szumera-Ciećkiewicz, Pawel P. Teterycz, Piotr R. Rutkowski, Robert V. Rawson, Richard A. Scolyer, John F. Thompson, Julia Newton-Bishop, Marguerite Stas, and et al. 2021. "Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas" International Journal of Molecular Sciences 22, no. 19: 10568. https://doi.org/10.3390/ijms221910568