An Evolutionary Cancer Epigenetic Approach Revealed DNA Hypermethylation of Ultra-Conserved Non-Coding Elements in Squamous Cell Carcinoma of Different Mammalian Species
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Study Population and Brushing Collection
2.3. Ultra-Conserved Non-Coding Element Selection and Primer Designing
2.4. DNA Methylation Analysis
3. Results
3.1. Methylation Plotter Analysis
3.2. Principal Component Analysis (PCA)
3.3. Receiver-Operating Characteristic (ROC) Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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ID | Sample | Diagnosis | Species | Breed | Location | Sex | Age |
---|---|---|---|---|---|---|---|
AP15289 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Skin (head) | Fs | 9 y |
AP8012 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Skin (chin) | Mc | 10 y |
AP11378 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Skin (ear) | Fs | 12 y |
AP11306 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 12 y |
AP18329 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 11 y |
AP18369 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 13 y |
AP4925 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 19 y |
AP9641 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 16 y |
AP9960 | FFPE | SCC | Felis catus (Cat) | Persian | Oral cavity | Mc | 11 y |
AP17845 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 11 y |
AP17919 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 10 y |
AP13806 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 15 y |
AP17595 | FFPE | SCC | Felis catus (Cat) | Thai | Oral cavity | Fs | 12 y |
AP17714 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 9 y |
AP18102 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 12 y |
AP768 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 15 y |
AP8694 | FFPE | SCC | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 12 y |
AP16359 | FFPE | SCC | Canis lupus familiaris (Dog) | Beagle | Prepuce | M | 12 y |
AP17735 | FFPE | SCC | Canis lupus familiaris (Dog) | Labrador retriever | Skin | F | 11 y |
AP16030 | FFPE | SCC | Canis lupus familiaris (Dog) | Labrador retriever | Oral cavity | Fs | 14 y |
AP7483 | FFPE | SCC | Equus ferus caballus (Horse) | Paint horse | Vulva | F | 15 y |
AP12812 | FFPE | SCC | Bos taurus (Bovine) | Holstein fresian | Eyelid | Mc | 8 y |
S17_3828 | FFPE | SCC | Meles meles (European badger) | Lung | F | 14 y | |
S18_5874 | FFPE | SCC | Hystrix cristata (Porcupine) | Mandible | F | 14 y | |
AP10728 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 9 y |
AP2633 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 10 y |
AP5978 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 7 y |
AP847 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 12 y |
AP18349 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 8 y |
AP16102 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 17 y |
AP17827 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 9 y |
AP17936 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 4 y |
AP18136 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 5 y |
AP18404 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 8 y |
AP2115 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 12 y |
AP498 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 1 y |
AP7692 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 13 y |
AP17076 | FFPE | Stomatitis | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 10 y |
CAT-1 | Brushing | Norm | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 15 y |
CAT-2 | Brushing | Norm | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 10 y |
CAT-3 | Brushing | Norm | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 9 y |
CAT-4 | Brushing | Norm | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 10 y |
CAT-5 | Brushing | Norm | Felis catus (Cat) | Domestic short-haired | Oral cavity | Fs | 9 y |
CAT-6 | Brushing | Norm | Felis catus (Cat) | Persian | Oral cavity | Fs | 11 y |
CAT-7 | Brushing | Norm | Felis catus (Cat) | Domestic short-haired | Oral cavity | Mc | 12 y |
DOG-1 | Brushing | Norm | Canis lupus familiaris (Dog) | Border Collie | Oral cavity | Mc | 5 y |
DOG-2 | Brushing | Norm | Canis lupus familiaris (Dog) | Golden Retriever | Oral cavity | Mc | 10 y |
DOG-3 | Brushing | Norm | Canis lupus familiaris (Dog) | Newfoundland | Oral cavity | Fs | 9 y |
DOG-4 | Brushing | Norm | Canis lupus familiaris (Dog) | Golden Retriever | Oral cavity | F | 7 y |
DOG-5 | Brushing | Norm | Canis lupus familiaris (Dog) | Golden Retriever | Oral cavity | F | 5 y |
HORSE-1 | Brushing | Norm | Equus ferus caballus (Horse) | Italian Saddle | Oral cavity | Mc | 16 y |
HORSE-2 | Brushing | Norm | Equus ferus caballus (Horse) | Italian Saddle | Oral cavity | Mc | 9 y |
HORSE-3 | Brushing | Norm | Equus ferus caballus (Horse) | Italian Saddle | Oral cavity | Mc | 8 y |
HORSE-4 | Brushing | Norm | Equus ferus caballus (Horse) | Italian Saddle | Oral cavity | F | 10 y |
HORSE-5 | Brushing | Norm | Equus ferus caballus (Horse) | Italian Saddle | Oral cavity | F | 9 y |
BOV-1 | Brushing | Norm | Bos taurus (Bovine) | Holstein fresian | Oral cavity | F | 2 y |
BOV-2 | Brushing | Norm | Bos taurus (Bovine) | Holstein fresian | Oral cavity | F | 1 y 6 m |
BADGER-1 | Brushing | Norm | Meles meles (European badger) | Oral cavity | F | Unknown (adult) |
UCNE Bejerano | UCNE ID | UCNE Name | Upstream Gene | Within Gene | Downstream Gene | Primer For | Primer Rev | Genome Coordinates (hg38) | Number of CpG | Amplicon Length |
---|---|---|---|---|---|---|---|---|---|---|
uc.160+ | 27423 | OTP_Lukas | AK128395 | NA | AP3B1 | TTTTTGATTTTAGGTGGAATTAGGAG | TACATTAAAACCTCAATTAATTAACCCTTA | Chr5+: 77972981−77973184 | 6 | 204 |
uc.283+ | 6661 | DRGX_Toru | DRGX | NA | ERCC6 | TTGGGTGAAAATTAAATTTTAAAGTAT | AAAAAACACTTAATAATACAAAAAACC | Chr10+: 49396679−49396856 | 6 | 178 |
uc.283 Prom | 6661 | DRGX_Toru | DRGX | NA | ERCC6 | TGTTTTTAGTAAGGGGTTTTTGAATT | AAAATTTAATTTTCACCCAAACAAA | Chr10+: 49396546−49396698 | 6 | 153 |
uc.416+ | NA | NA | HOXB4 | HOXB5 | HOXB6 | GTTTTAAAGTGGTTGGAGGAGGT | CTATCAATTACTAAATTATAACAATAACAA | Chr17+: 48593480−48593629 | 7 | 150 |
uc.339+ | NA | NA | ATP5G2 | NA | KIAA1536 | GTTATTATAGGAATGTAATTTTGTT | CCTTTCAAAAACTCAAAACCATAAA | Chr12+: 53677385−53677558 | 9 | 174 |
uc.270+ | 35244 | NA | AB040954 | MAPKAP1 | LOC51145 | GTGATGGGTATTTAGAGAGTTGGTTAT | CTTACCAAAAATCATTATTCACCCT | Chr9+: 125541877−125541998 | 7 | 122 |
uc.299+ | NA | NA | HIF1AN | PAX2 | C10orf6 | TTTTGTTGTGTGTGGGGTGT | CCTCACCTACCCAAAATTTTACTAAC | Chr10+: 100749700−100749920 | 12 | 221 |
uc.328+ | NA | NA | ELP4 | PAX6 | RCN1 | TTTGATATTTGTTTTTAAAATAAAATTAGT | ACAAAATAACAAAACTACCACAAAC | Chr11+: 31804130−31804274 | 6 | 145 |
UCNE | Best Position | Best AUC Value | Worst Position | Worst AUC Value | Best to Worst AUC Gap |
---|---|---|---|---|---|
uc.160 | 77268955 | 0.783 | 77268898 | 0.725 | 0.058 |
uc.270 | 128304242 | 0.814 | 128304236 | 0.589 | 0.225 |
uc.283 | 50604683 | 0.824 | 50604779 | 0.653 | 0.171 |
uc.299 | 102509546 | 0.752 | 102509564 | 0.686 | 0.066 |
uc.328 | 31825751 | 0.713 | 31825744 | 0.624 | 0.089 |
uc.339 | 54071206 | 0.826 | 54071264 | 0.742 | 0.084 |
uc.416 | 46670879 | 0.843 | 46670918 | 0.679 | 0.164 |
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Morandi, L.; Sabattini, S.; Renzi, A.; Rigillo, A.; Bettini, G.; Dervas, E.; Schauer, A.; Morandi, M.; Gissi, D.B.; Tarsitano, A.; et al. An Evolutionary Cancer Epigenetic Approach Revealed DNA Hypermethylation of Ultra-Conserved Non-Coding Elements in Squamous Cell Carcinoma of Different Mammalian Species. Cells 2020, 9, 2092. https://doi.org/10.3390/cells9092092
Morandi L, Sabattini S, Renzi A, Rigillo A, Bettini G, Dervas E, Schauer A, Morandi M, Gissi DB, Tarsitano A, et al. An Evolutionary Cancer Epigenetic Approach Revealed DNA Hypermethylation of Ultra-Conserved Non-Coding Elements in Squamous Cell Carcinoma of Different Mammalian Species. Cells. 2020; 9(9):2092. https://doi.org/10.3390/cells9092092
Chicago/Turabian StyleMorandi, Luca, Silvia Sabattini, Andrea Renzi, Antonella Rigillo, Giuliano Bettini, Eva Dervas, Alexandria Schauer, Marco Morandi, Davide B. Gissi, Achille Tarsitano, and et al. 2020. "An Evolutionary Cancer Epigenetic Approach Revealed DNA Hypermethylation of Ultra-Conserved Non-Coding Elements in Squamous Cell Carcinoma of Different Mammalian Species" Cells 9, no. 9: 2092. https://doi.org/10.3390/cells9092092