Association of TNFRSF10D DNA-Methylation with the Survival of Melanoma Patients
Abstract
:1. Introduction
2. Results and Discussion
2.1. Training Set for Selection of Relevant Genes
2.2. Test Set for the Validation of Relevant Genes
(A) Training Set | ||||
---|---|---|---|---|
Variable | Overall Survival | Relapse-Free Survival | ||
No. Patients (Died/Total) | p-Value (Log-Rank-Test) | No. Patients (Relapsed/Total) | p-Value (Log-Rank-Test) | |
Sex | ||||
Male | 12/24 | 0.712 | 11/24 | 0.717 |
Female | 5/12 | 5/12 | ||
Age | ||||
<60 | 9/24 | 0.049 | 10/24 | 0.239 |
≥60 | 8/12 | 6/12 | ||
Clark level | ||||
2/3 | 4/11 | 0.001 | 3/11 | <0.001 |
4 | 9/21 | 9/21 | ||
5 | 4/4 | 4/4 | ||
Ulceration | ||||
No | 7/22 | 0.015 | 7/22 | 0.046 |
Yes | 10/14 | 9/14 | ||
Tumor thickness | ||||
≤2 mm (T1/T2) | 5/13 | 0.008 | 6/13 | 0.008 |
2.01–4 mm (T3) | 2/8 | 1/8 | ||
≥4.01 mm (T4) | 10/15 | 9/15 | ||
Mitotic rate | ||||
≤1/mm2 | 3/12 | 0.026 | 3/12 | 0.052 |
>1/mm2 | 14/24 | 13/24 | ||
Interferon alpha therapy | ||||
No | 15/28 | 0.302 | 14/28 | 0.374 |
Yes | 2/8 | 2/8 | ||
TNFRSF10D | ||||
Unmethylated | 11/29 | 0.001 | 11/29 | 0.008 |
Methylated | 6/7 | 5/7 | ||
(B) Test Set | ||||
Sex | ||||
Male | 5/12 | 0.929 | 5/12 | 0.98 |
Female | 10/20 | 9/20 | ||
Age | ||||
<60 | 7/22 | 0.003 | 7/22 | 0.031 |
≥60 | 8/10 | 7/10 | ||
Clark level | ||||
2/3 | 3/7 | <0.001 | 3/7 | <0.001 |
4 | 6/18 | 5/18 | ||
5 | 6/6 | 6/6 | ||
Ulceration | ||||
No | 11/23 | 0.887 | 10/23 | 0.942 |
Yes | 4/9 | 4/9 | ||
Tumor thickness | ||||
≤2 mm (T1/T2) | 5/12 | 0.919 | 5/12 | 0.992 |
2.01–4 mm (T3) | 7/13 | 6/13 | ||
≥4.01 mm (T4) | 2/5 | 2/5 | ||
Mitotic rate | ||||
≤1/mm2 | 6/18 | 0.077 | 6/18 | 0.141 |
>1/mm2 | 9/14 | 8/14 | ||
Interferon alpha therapy | ||||
No | 9/24 | 0.003 | 8/24 | 0.002 |
Yes | 6/8 | 6/8 | ||
TNFRSF10D | ||||
Unmethylated | 11/28 | 0.041 | 10/28 | 0.012 |
Methylated | 4/4 | 4/4 | ||
Sex | ||||
Male | 17/36 | 0.683 | 16/36 | 0.734 |
Female | 15/32 | 14/32 | ||
Age | ||||
<60 | 16/46 | <0.001 | 13/22 | 0.013 |
≥60 | 16/22 | 23/74 | ||
Clark level | ||||
2/3 | 7/18 | <0.001 | 6/18 | 0.011 |
4 | 15/39 | 14/39 | ||
5 | 10/10 | 10/10 | ||
Ulceration | ||||
No | 18/45 | 0.085 | 17/45 | 0.116 |
Yes | 14/23 | 13/23 | ||
Tumor thickness | ||||
≤2 mm (T1/T2) | 10/25 | 0.084 | 11/25 | 0.113 |
2.01–4 mm (T3) | 9/21 | 7/21 | ||
≥4.01 mm (T4) | 12/20 | 11/20 | ||
Mitotic rate | ||||
≤1/mm2 | 9/30 | 0.005 | 9/30 | 0.012 |
>1/mm2 | 23/38 | 21/38 | ||
Interferon alpha therapy | ||||
No | 24/52 | 0.261 | 22/52 | 0.24 |
Yes | 8/16 | 8/16 | ||
TNFRSF10D | ||||
Unmethylated | 22/57 | <0.001 | 21/57 | <0.001 |
Methylated | 10/11 | 9/11 |
2.3. Overall Prognostic Significance Merging the Training and the Test Set
Variable | Overall Survival | Relapse-Free Survival | ||
---|---|---|---|---|
RR of Death (95% CI) | p-Value | RR of Relapse or Progression (95% CI) | p-Value | |
Sex | ||||
Male | 0.5 (0.2–1.6) | 0.11 | 0.4 (0.2–0.9) | 0.03 |
Female | ||||
Age | ||||
<60 | 2.1 (0.9–4.6) | 0.07 | 1.6 (0.75–4.1) | 0.20 |
≥60 | ||||
Clark level | ||||
2/3 | 3.0 (1.6–5.9) | 0.001 | 4.9 (2.4–10.1) | <0.001 |
4 | ||||
5 | ||||
Ulceration | ||||
No | 1.4 (0.6–3.5) | 0.47 | 1.1 (0.5–2.8) | 0.78 |
Yes | ||||
Tumor thickness | ||||
≤2 mm (T1/T2) | 0.9 (0.6–1.6) | 0.82 | 0.8 (0.5–1.3) | 0.39 |
2.01–4 mm (T3) | ||||
≥4.01 mm (T4) | ||||
Mitotic rate | ||||
≤1/mm2 | 1.4 (0.5–3.9) | 0.49 | 1.6 (0.6–4.5) | 0.37 |
>1/mm2 | ||||
Interferon alpha therapy | ||||
No | 2.2 (0.8–5.9) | 0.11 | 2.7 (1.1–7.5) | 0.03 |
Yes | ||||
TNFRSF10D | ||||
Unmethylated | 4.6 (2.0–11.0) | <0.001 | 7.2 (2.8–18.3) | <0.001 |
Methylated |
2.4. Discussion
3. Experimental Section
3.1. The Patient Study Cohort and Study Design
3.2. DNA Extraction and Bisulfite Conversion from Formalin-Fixed Paraffin-Embedded (FFPE) Tissues
3.3. DNA Methylation Analysis
3.4. Mitotic Rate
3.5. Statistical Analysis
4. Conclusions
Supplementary Files
Supplementary File 1Acknowledgments
Author Contributions
Conflicts of Interest
References
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Ratzinger, G.; Mitteregger, S.; Wolf, B.; Berger, R.; Zelger, B.; Weinlich, G.; Fritsch, P.; Goebel, G.; Fiegl, H. Association of TNFRSF10D DNA-Methylation with the Survival of Melanoma Patients. Int. J. Mol. Sci. 2014, 15, 11984-11995. https://doi.org/10.3390/ijms150711984
Ratzinger G, Mitteregger S, Wolf B, Berger R, Zelger B, Weinlich G, Fritsch P, Goebel G, Fiegl H. Association of TNFRSF10D DNA-Methylation with the Survival of Melanoma Patients. International Journal of Molecular Sciences. 2014; 15(7):11984-11995. https://doi.org/10.3390/ijms150711984
Chicago/Turabian StyleRatzinger, Gudrun, Simone Mitteregger, Barbara Wolf, Regina Berger, Bernhard Zelger, Georg Weinlich, Peter Fritsch, Georg Goebel, and Heidelinde Fiegl. 2014. "Association of TNFRSF10D DNA-Methylation with the Survival of Melanoma Patients" International Journal of Molecular Sciences 15, no. 7: 11984-11995. https://doi.org/10.3390/ijms150711984