13-gene DNA Methylation Analysis from Oral Brushing: A Promising Non Invasive Tool in the Follow-up of Oral Cancer Patients
Abstract
:1. Introduction
2. Experimental Section
2.1. Ethics Statement
2.2. Population Study
2.3. DNA Methylation Analysis
2.4. Statistical Analysis
3. Results
3.1. Gene DNA Methylation Analysis
3.1.1. Before Surgery
3.1.2. After Surgery
3.2. Loco-Regional Disease-Free Survival
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Patient | Site of Index Tumor | Site of Secondary Tumor | TNM Stage of Index Tumor | Perineural Invasion | Vascular Invasion | Histological Grade | Status of Surgical Margin | Presence of Concomitant OPMD | DNA Methylation Score in OSCC Sample (pre-treatment) | DNA Methylation Score in Regenerative Area (post-treatment) |
---|---|---|---|---|---|---|---|---|---|---|
Case 1 | Palate | Palate | T1N0M0 | Yes | Yes | G2 | Clear | No | 7.29 (POSITIVE) | 8.88 (POSITIVE) |
Case 3 | Superior gum/hard palate | Superior gum/hard palate | T2N2bM0 | No | No | G2 | Clear | No | 3.39 (POSITIVE) | 2.76 (POSITIVE) |
Case 6 | Superior gum/hard palate | Superior gum/hard palate | T1N0M0 | No | No | G2 | Close | Lichen | 2.51 (POSITIVE) | 1.15 (POSITIVE) |
Case 15 | Right tongue | Left tongue | T2N3M0 | Yes | No | G2 | Clear | No | 3.68 (POSITIVE) | 3.39 (POSITIVE) |
Case 27 | Superior gum/palate | palate | T2N0M0 | Yes | Yes | G3 | Clear | No | 5.21 (POSITIVE) | 3.38 (POSITIVE) |
Case 33 | Hard palate | Hard palate | T1N0M0 | No | No | G1 | Clear | Lichen | 2.51 (POSITIVE) | 1.69 (POSITIVE) |
Case 35 | Right Cheek | Lymph node metastasis | T3N0M0 | No | No | G3 | Clear | No | 1.97 (POSITIVE) | 0.73 (NEGATIVE) |
Clinico-Pathological Variables | Patients | Positive Score Regenerative Mucosa | p | Relapse (LR, SPT or LNM) | ||
---|---|---|---|---|---|---|
N Patients | % Patients | p | ||||
Sex | ||||||
Male | 19 | 4 | p = 0.07 | 1 | 5.3% | p = 0.06 |
Female | 30 | 12 | 6 | 20% | ||
Age | ||||||
< 65 | 18 | 4 | p = 0.234 | 1 | 5.5% | p = 0.07 |
> 65 | 31 | 12 | 6 | 19.5% | ||
Site | ||||||
Tongue | 17 | 3 | p = 0.07 | 1 | 5.9% | p = 0.07 |
Floor of mouth | 1 | 0 | 0 | 0 | ||
Cheek | 4 | 0 | 1 | 25% | ||
Soft palate | 0 | 0 | 0 | 0 | ||
Superior gum/hard palate | 7 | 5 | 2 | 28.6% | ||
Inferior gum | 19 | 8 | 3 | 15.8% | ||
Lip | 1 | 0 | 0 | 0 | ||
Grading | ||||||
G1 | 20 | 7 | p = 0.37 | 1 | 5% | p = 0.06 |
G2 | 21 | 8 | 6 | 28.6% | ||
G3 | 8 | 1 | 0 | 0 | ||
T stage | ||||||
T1–2 = 0 | 28 | 9 | p = 0.93 | 6 | 21.4% | p = 0.08 |
T3–4 = 1 | 21 | 7 | 1 | 4.7% | ||
N positivity | ||||||
N0 | 42 | 14 | p = 0.81 | 6 | 14.3% | p = 0.93 |
N+ | 7 | 2 | 1 | 14.3% | ||
Perineural invasion | ||||||
No | 42 | 13 | p = 0.53 | 4 | 9.5% | p = 0.0004 * |
Yes | 7 | 3 | 3 | 42.8% | ||
Vascular invasion | ||||||
No | 46 | 13 | p = 0.06 | 5 | 10.9% | p = 0.000006 * |
Yes | 3 | 3 | 2 | 66.7% | ||
Margin of resection tumor | ||||||
Clear | 45 | 14 | p = 0.35 | 6 | 13.3% | p = 0.48 |
Close | 3 | 2 | 1 | 33.4% | ||
Dysplasia | 1 | 0 | 0 | 0 | ||
Presence of OPMD | ||||||
No | 42 | 13 | p = 0.26 | 5 | 11.9% | p = 0.38 |
Oral Lichen Planus | 5 | 3 | 2 | 40% | ||
Leukoplakia | 2 | 0 | 0 | 0 | ||
Adjuvant Radiotherapy | ||||||
No | 27 | 9 | p = 0.91 | 3 | 11.1% | p = 0.58 |
Yes | 22 | 7 | 4 | 18.2% | ||
Reconstructive flap | ||||||
No | 23 | 7 | p = 0.75 | 3 | 13.1% | p = 0.73 |
Yes | 26 | 9 | 4 | 15.4% | ||
Score in regenerative area | ||||||
Negative | 33 | 1 | 3.1% | p = 0.0002 * | ||
Positive | 16 | 6 | 37.5% |
Factor | Df | Hazard Ratio | p-Value |
---|---|---|---|
Perineural invasion | 1 | 7.84 (1.28–48.12) | 0.0279 |
Positive score in regenerative area | 1 | 15.02 (1.7–130.2) | 0.0024 |
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Gissi, D.B.; Tarsitano, A.; Gabusi, A.; Rossi, R.; Attardo, G.; Lenzi, J.; Marchetti, C.; Montebugnoli, L.; Foschini, M.P.; Morandi, L. 13-gene DNA Methylation Analysis from Oral Brushing: A Promising Non Invasive Tool in the Follow-up of Oral Cancer Patients. J. Clin. Med. 2019, 8, 2107. https://doi.org/10.3390/jcm8122107
Gissi DB, Tarsitano A, Gabusi A, Rossi R, Attardo G, Lenzi J, Marchetti C, Montebugnoli L, Foschini MP, Morandi L. 13-gene DNA Methylation Analysis from Oral Brushing: A Promising Non Invasive Tool in the Follow-up of Oral Cancer Patients. Journal of Clinical Medicine. 2019; 8(12):2107. https://doi.org/10.3390/jcm8122107
Chicago/Turabian StyleGissi, Davide B., Achille Tarsitano, Andrea Gabusi, Roberto Rossi, Giuseppe Attardo, Jacopo Lenzi, Claudio Marchetti, Lucio Montebugnoli, Maria P. Foschini, and Luca Morandi. 2019. "13-gene DNA Methylation Analysis from Oral Brushing: A Promising Non Invasive Tool in the Follow-up of Oral Cancer Patients" Journal of Clinical Medicine 8, no. 12: 2107. https://doi.org/10.3390/jcm8122107