**5. Conclusion**

40 Biomarker

The survival tables can allow us to compare two or more groups of patients. In this case, the first thing we should do is draw the survival curves for the two (or more) groups on the same graph. Statistical methods are important here, because we cannot make judgments simply on the basis of the amount of separation between the curves; a small difference may be statistically significant if the sample size is large, and a large difference may not if the sample size is small. We have mainly two methods to determine if the differences are statistically significant: the Wilcoxon rank sum test and the log rank test. Figure 6 shows comparative survival curves for pediatric and adult patients diagnosed with MDS treated

Fig. 6. Overall survival of primary MDS patients treated with allogeneic HSCT, pediatric patients

In the Rodrigues et al (2010) study, the authors studied the methylation status of the p15INK4B and p16INK4A genes in 47 pediatric patients with MDS, its correlation with subtype, and the role of p15INK4B and p16INK4A in the evolution of MDS toward AML. The results obtained suggest that methylation of these genes is an epigenetic biomarker of pediatric disease evolution. The authors used some statistical tools presented here. For example, the correlation between p15INK4B gene methylation status and subtypes of pediatric primary MDS, considering initial stage RC, and later stages RAEB and RAEB-t, was assessed by the chi-square test, which is a nonparametric test. The statistical analysis suggested that the frequency of p15INK4B gene methylation was significantly higher in later stages of disease compared with the initial stage, with p-value < 0.003. The correlation between p16INK4A gene methylation status and subtypes of pediatric primary MDS was also assessed by the chisquare test, with a slight modification. In fact, it is a correction factor, which is necessary when we have a small number of data. This is known as chi-square with continuity

versus adult patients.

with allogeneic hematopoietic stem cell transplantation (HSCT).

The field of cancer epigenetics is evolving rapidly. Advances in the understanding of chromatin structure, histone modifications, DNA methylation and transcriptional activity have resulted in an increasingly integrated view of epigenetics. These discoveries lead to the development of new treatments in cancer using epigenetic therapies. The MDS comprises a complex spectrum of hematopoietic stem cell disorders, where the study of epigenetics has brought new knowledge about the development and evolution of this disease to AML. Other important points in epigenetics studies in MDS were the introduction of the treatments using hypomethylant drugs and histone deacethylases inhibitors. The MDS may be considered a good model to study the epigenetics in the cancer pathogenesis research and the applicability in clinical. The identification of biomarkers of diagnosis and prognosis in MDS will possibility the elaboration of new classification and score prognostic systems and will help to understand the different pathways involved in the MDS pathogenesis. With the advance of the technologies involving epigenome projects, future research in the epigenetic therapies will be the development of inhibitors with specificity to particular biomarkers.

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