Review Metabolic profiling of pteridines for determination of potential biomarkers in cancer diseases Cancer disease is the second leading cause of death in the world. Epidemiology data indicate that early diagnosis of a tumour increases a patient’s chance of recovery. Biomarkers are effective instruments which can potentially lead to precancer screening or precancer diagnosis and may provide useful information on the cancer type and the disease’s stage of progression. The analysis of new biomarkers for cancer is currently a popular area of study in clinical and cancer research. Pteridines are a class of potential cancer biomarkers. The monitoring levels of pteridines may have prospective value for controlling the course of the malignant process. This review describes the functional employment of pteridines, as biomarkers, in cancer diagnosis. It also contains the description of application of analytical techniques such as high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) used for pteridine analysis. Keywords: Biomarkers / Cancer / Electromigration techniques / Metabolomics / Pteridines DOI 10.1002/elps.201000664 1 Introduction Cancer is one of the major health problems in modern world. Many medical and health institutions, scientists, and physicians focus their work and interest on early detection and treatment of cancer diseases. General clinical data have shown that when cancer is discovered earlier, the successful treatment chances will be higher. Precancer diagnosis has become a hot point of clinical and preclinical research with the development of biochemistry and analytical instrumenta- tion. It is extremely important to find good and appropriate markers, to make early diagnosis possible before the macroscopic symptoms of disease. As precancer studies progress, cancer biomarkers become more and more apparent as containing useful information such as the possible cancer type and the stage of the patient’s progression at a very early time. Biomarkers are compounds in the body fluids or tissues that can testify to medical conditions or biological states. Already discovered biomarkers have been used in the detection of several diseases [1–3]. An ideal cancer biomarker should fulfill the following conditions: high sensitivity and specificity; it must be absolutely reliable and possible; it should be able to reliably detect all cancers of the same type. Cancer biomarkers have to significantly change the following cancer remission. If a cancer biomarker is intended to be used for screening procedures, the cancer biomarker needs to be tumor-specific. Similarly, for the clinical follow-up of patients already diagnosed with cancer, a biomarker should be clearly related to the cancer disease. Ideal cancer biomarkers should also be readily detectable in body fluids and tissue extracts. Most of the cancer markers employed today exist also in elevated form in some nonmalignant conditions. There is a number of false-positive or false-negative predictions in the case of markers such as carcinoembrionic antigen (CEA), a-fetoprotein (AFP), and other glycoproteins, enzymatic, and hormonal markers [4]. Such compounds that can serve as cancer markers are pteridines which are low-molecular-weight molecules belonging to a class of metabolites. Pteridines are important cofactors in the process of cell metabolism and their levels have significant importance in clinical diagnosis. They are excreted by humans in urine and the levels of pteridines have been found to elevate significantly when the cellular immune system is activated by certain diseases such as cancer [3]. 2 Pteridines – structure and metabolism Pteridines constitute a large and structurally varied group of natural compounds involved in the biosynthetic pathways of cofactors and vitamins. Their derivatives are designated by Piotr Kos ´ lin ´ ski 1 Renata Bujak 1 Emilia Daghir 1 Michal J. Markuszewski 1,2 1 Department of Toxicology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland 2 Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdan ´ sk, Gdan ´ sk, Poland Received December 14, 2010 Revised February 4, 2011 Accepted February 5, 2011 Abbreviations: BIO, biopterin; GTP, guanosine triphosphate; HILC, hydrophilic interaction LC; NP, neopterin; 6-HMP, 6-hydroxymethylpterin Correspondence: Dr. Micha" J. Markuszewski, Department of Toxicology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, M. Curie-Sk"odowskiej 9, 85-094 Bydgoszcz, Poland E-mail: michal.markuszewski@cm.umk.pl Fax: 148-52-585-38-04 & 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.electrophoresis-journal.com Electrophoresis 2011, 32, 2044–2054 2044