Pre-Operative Evaluation of DNA Methylation Profile in Oral Squamous Cell Carcinoma Can Predict Tumor Aggressive Potential
Abstract
:1. Introduction
2. Results
2.1. Pathological Findings and Tumor Stage
2.2. Methylation Profile and Clinical-Pathological Characteristics
2.3. Methylation Profile and Adverse Event (AE)
3. Discussion
4. Materials and Methods
4.1. Ethics Statement
4.2. Study Setting and Data Collection
4.3. Treatment Modality
4.4. DNA Methylation Analysis
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AE | Adverse Event |
NGS | Next Generation Sequencing |
OSCC | Oral Squamous Cell Carcinoma |
PNI | Perineural invasion |
POI | Pattern of infiltration |
WPOI | Worst pattern of infiltration |
DOI | Depth of Invasion |
HR | Hazard Ratio |
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Clinical-Pathological Variables | ||||
---|---|---|---|---|
Patients | Relapses Observed | p-Value | ||
Sex | Male | 17 (47%) | 6 (35%) | 0.82 |
Female | 19 (53%) | 6 (31%) | ||
Age | <65 | 15 (42%) | 8 (53%) | 0.35 |
>65 | 21 (58%) | 4 (19%) | ||
Smoke | Yes | 7 (19%) | 3 (43%) | 0.26 |
No | 29 (81%) | 9 (31%) | ||
Site | Tongue and floor of mouth | 13 (36%) | 4 (31%) | 0.96 |
Buccal and labial mucosa | 7 (19%) | 3 (43%) | ||
Gingiva, Hard Palate, Retromolar region | 16 (45%) | 5 (31%) | ||
T stage | T1-T2 | 27 (75%) | 8 (29%) | 0.33 |
T3-T4 | 9 (25%) | 4 (44%) | ||
N stage | N− | 32 (89%) | 9 (28%) | 0.06 |
N+ | 4 (11%) | 3 (75%) | ||
Grading | G1 | 20 (56%) | 5 (25%) | 0.18 |
G2 | 14 (39%) | 6 (43%) | ||
G3 | 2 (5%) | 1(50%) | ||
Surgical margins | Free | 29 (81%) | 9 (31%) | 0.83 |
Close | 4 (11%) | 1 (25%) | ||
Displasia | 3 (8%) | 2 (66%) | ||
Involved | 0 (0%) | |||
Presence of associated OPMD | None | 26 (72%) | 11 (42%) | 0.07 |
Lichen | 6 (17%) | 0 (0%) | ||
Leucoplakia | 4 (11%) | 1 (25%) | ||
Depth of invasion (DOI) | <4 mm | 21 (58%) | 5 (24%) | 0.07 |
>4 mm | 15 (42%) | 7 (47%) | ||
Pattern of invasion | P1-P2 | 22 (61%) | 4 (18%) | 0.01 * |
P3-P4 | 14 (39%) | 8 (57%) | ||
Radiotherapy | Yes | 8 (22%) | 4 (50%) | 0.2 |
No | 28 (78%) | 8 (29%) |
CpG Site | Ln HR | HR | p-Value |
---|---|---|---|
EPHX3-24 (Chr19:15232040) | −0.0234 | 0.9769 | 0.0157 |
EPHX3-26 (Chr19:15232034) | −0.0226 | 0.9777 | 0.0172 |
ITGA4-3 (Chr2:181458175) | 0.0163 | 1.0165 | 0.0078 |
ITGA4-4 (Chr2:181458181) | 0.0306 | 1.0310 | 0.0027 |
MiR193-3 (Chr17:31559856) | 0.0089 | 1.0090 | 0.0099 |
Integrated Brier score | 0.080 | ||
C-index | 0.802 | ||
Integrated AUC | 0.850 |
CpG Site | Ln HR | HR | p-Value |
---|---|---|---|
ITGA4-3(Chr2:181458175) | 0.0616 | 1.0636 | 0.0001 |
ITGA4-4(Chr2:181458181) | 0.0467 | 1.0478 | 0.0003 |
ITGA4-7(Chr2: 181458229) | 0.0176 | 1.0177 | 0.0046 |
ITGA4-12(Chr2: 181458289) | 0.0152 | 1.0153 | 0.0052 |
Integrated Brier score | 0.059 | ||
C-index | 0.892 | ||
Integrated AUC | 0.903 |
Gene | Map | Position | Amplicon Length | Position Respect to TSS | Number of Interrogated CpG | hg38 Coordinates |
---|---|---|---|---|---|---|
ZAP70 | 2q11.2 | Exon 3 | 180 | 10728 | 20 | Chr2: 97724265-97724445 |
GP1BB | 22q11.21 | Exon 1 | 192 | 363 | 18 | Chr22: 19723282-19723460 |
KIF1A | 2q37.3 | Exon 1 | 189 | −1 | 27 | Chr2: 240820168-240820310 |
PARP15 | 3q21.1 | Exon 1 | 206 | 93 | 19 | Chr3:122577695-122577901 |
ITGA4 | 2q31.3 | Exon 2 | 214 | 912 | 14 | Chr2:181457647-181457879 |
NTM | 11q25 | Exon 1 | 190 | 62 | 15 | Chr11:131911126-131911314 |
MIR193A | 17q11.2 | Promoter | 256 | −178 | 26 | Chr17:31559818-31560073 |
EPHX3 | 19p13.12 | Exon 1 | 223 | 215 | 29 | Chr19:15231995-15232217 |
LINC00599 | 8p23.1 | Exon 1 | 199 | 69 | 20 | Chr8:9903205-9903403 |
FLI1 | 11q24.3 | Exon 1 | 186 | 187 | 12 | Chr11:128694103-128694288 |
MIR296 | 20q13.32 | Exon 1 | 238 | 180 | 15 | Chr20:58817149-58817363 |
LRRTM1 | 2p12 | Promoter | 179 | −431 | 24 | Chr2:80304527-80304705 |
TERT | 5p15.33 | Intron4-5 | 109 | 14976 | 6 | Chr5:1279604-1279759 |
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Gissi, D.B.; Fabbri, V.P.; Gabusi, A.; Lenzi, J.; Morandi, L.; Melotti, S.; Asioli, S.; Tarsitano, A.; Balbi, T.; Marchetti, C.; et al. Pre-Operative Evaluation of DNA Methylation Profile in Oral Squamous Cell Carcinoma Can Predict Tumor Aggressive Potential. Int. J. Mol. Sci. 2020, 21, 6691. https://doi.org/10.3390/ijms21186691
Gissi DB, Fabbri VP, Gabusi A, Lenzi J, Morandi L, Melotti S, Asioli S, Tarsitano A, Balbi T, Marchetti C, et al. Pre-Operative Evaluation of DNA Methylation Profile in Oral Squamous Cell Carcinoma Can Predict Tumor Aggressive Potential. International Journal of Molecular Sciences. 2020; 21(18):6691. https://doi.org/10.3390/ijms21186691
Chicago/Turabian StyleGissi, Davide B., Viscardo P. Fabbri, Andrea Gabusi, Jacopo Lenzi, Luca Morandi, Sofia Melotti, Sofia Asioli, Achille Tarsitano, Tiziana Balbi, Claudio Marchetti, and et al. 2020. "Pre-Operative Evaluation of DNA Methylation Profile in Oral Squamous Cell Carcinoma Can Predict Tumor Aggressive Potential" International Journal of Molecular Sciences 21, no. 18: 6691. https://doi.org/10.3390/ijms21186691
APA StyleGissi, D. B., Fabbri, V. P., Gabusi, A., Lenzi, J., Morandi, L., Melotti, S., Asioli, S., Tarsitano, A., Balbi, T., Marchetti, C., & Montebugnoli, L. (2020). Pre-Operative Evaluation of DNA Methylation Profile in Oral Squamous Cell Carcinoma Can Predict Tumor Aggressive Potential. International Journal of Molecular Sciences, 21(18), 6691. https://doi.org/10.3390/ijms21186691