However, as our study was limited to a short follow-up period and a small number of cases, more extensive studies are needed to confirm the prognostic value of the CSC populations in post-chemotherapy specimens, especially, according to different chemotherapeutic regimens.
It is unclear whether this specific set of DNA methylation biomarkers provides any early predictive or prognostic value, and further and more extensive studies are required.
Promising prognostic biomarkers (to be further tested for their predictive ability) are emerging in the peripheral circulation [ 94– 97], and the accessibility of the synovial tissue through minimally invasive techniques [ 98] allows more extensive studies aimed at investigating the clinical and prognostic significance of different pathological features [ 99, 100].
The ability to use these initial signalling molecules as prognostic or predictive biomarkers awaits much more extensive investigations.
We speculate that meQTLs in the CDH13 promoter may serve as potential prognostic markers for an increased risk to trigger more extensive changes in the DNA methylation pattern.
Extensive prognostic analysis defined the strength of many known predictors more precisely, yielded new predictors and has resulted in validated prognostic models for use in moderate and severe TBI [ 5].
Nevertheless, more extensive study is needed to establish a role for PRMT1 as a potential biological prognostic marker.
In our previous paper we reported, that higher concentrations of 8-IP in EBC are found in a more extensive disease (radiological stage III), that raises hopes, that this marker could have a prognostic value [ 9].
Furthermore, owing to the retrospective nature of this analysis, there may exist a selection bias where those patients who underwent a more extensive lymphadenectomy may have had less comorbidity, as well as having tumours with more favourable prognostic features.
While the clinical application of our findings requires more extensive retrospective and prospective validations in additional and larger cohorts of patients, further studies to evaluate the prognostic significance of h TERT by FISH is also warranted.
