**3. Current advances in developing systemic biomarkers**

Systemic biomarkers approach is a relatively new area of biomedicine. However, over two decades of its existence [64], significant advances have been made. Great effort spent in this area not only improved analytical algorithms, but also underlined the importance of personalized approach. For example, many prognostic markers have been suggested for breast cancer in the literature, in particular for predicting survival. But data collected in separate studies led to striking discovery of the lack of overlap of the predictive genes in most of these studies. This emphasized the need of personalized approach even within tumor groups that share the same histomorphology [65]. The reason for discrepancies is debatable—divergent patterns of expression profiles might have been due to several analytical factors considered in the present chapter, but the solution holds the same: systemic biomarkers are only informative when patterns of pathways activation, rather than changes in individual genes expression, are analyzed. This idea led foundation to development of several analytical tools and panels. Our lab developed an NFE2L2/ AP-1 pathway-based systemic biomarker for assessing slight changes in physiological parameters of the human organism using peripheral blood leukocytes as the preferred sample type [66]. The same systemic approach utilizing another set of oxidative status markers was successfully used for unveiling features of uterine cervical incompetence patients [67]. Other labs also successfully apply pathway activation-based technologies in various field and other sample types, with special attention paid to fresh solid tumors samples and paraffin blocks [68]. Of note, Oncofinder technology [69, 70] and Oncotype DX assay [71] are among the most effective interactomics/multi-gene analysis-based tests in oncology.

In **Table 1**, some examples of suitable NFE2L2/AP-1 targets and complex markers are given along with their diagnostic properties (only area under the curve (AUC) is given, please see details in the cited publications).

As seen from **Table 1**, not only the markers may highly vary in nature, but they have different receiver operator characteristics. Notably, for each model to be studied, it is possible to choose or find a set of markers having extremely high AUCs that are hardly achievable using the traditional biomarker approaches.


**Acknowledgements**

**Conflict of interest**

corporate group.

present chapter.

**Author details**

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\*Address all correspondence to: p.zolotukhin@icloud.com

Biomedical Innovations LLC, Rostov-on-Don, Russia

The chapter preparation was funded by Biomedical Innovations LLC, a part of Evolution

Oxidative Status Pathways: Systemic Biomarkers http://dx.doi.org/10.5772/intechopen.75543 105

The authors claim that there were no financial or other conflicts of interests related to the

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**Table 1.** The NFE2L2/AP-1 pathway functioning markers used in two in vitro and in vivo studies, with AUC in descending order within each study.
