Jarkko Romppanen Serum Sialic Acid in Clinical Diagnostics

N-acetylneuraminic acid (referred to as sialic acid) is a negatively charged nine-carbon monosaccharide commonly attached to the carbohydrate chains of glycoproteins and glycolipids. An elevation in the serum sialic acid (SA) concentration has been observed in a number of cancer types and recently also in alcohol abusers. In the present study, serum SA concentrations in patients with breast cancer and benign breast disease, prostate cancer and benign prostate disease, children with different malignancies, alcohol abusers, and healthy controls were determined using high performance liquid chromatography (HPLC). Based on the SA levels in different patient groups and healthy controls, the diagnostic utility of SA was studied using receiver operating characteristic (ROC) analysis. Furthermore, serum total sialic acid (TSA) reference values for healthy controls were determined using a high performance anion-exchange chromatography with pulsed amperometric detection method (HPAE-PAD). HPAE-PAD is a simple and effective way to determine sialic acid without the need for derivatization. The HPAE-PAD system was clearly sensitive enough to allow the detection of the SA concentrations present in human serum. On its own serum sialic acid was not found to provide reliable classification of undefined breast tumours. The logistic regression model combining TSA, prostate-specific antigen (PSA) and free to total PSA ratio with digital rectal examination results possessed good diagnostic accuracy in discriminating patients with prostate cancer from patients with benign prostate hyperplasia. Serum TSA and TSA to total protein ratio could provide some assistance in exclusion and follow-up of children with malignancies, but infection must be taken into account when interpreting increased sialic acid values. Finally, serum sialic acid measurements may be useful in the assessment of drinking problems especially in conditions where the secondary effects of liver disease hamper the use of the traditional biomarkers. National Library of Medicine Classification: QZ 200, WB 141, WM 274, WI 725, QU 84 Medical Subject Headings: N-acetylneuraminic acid/blood; N-acetylneuraminic acid/diagnostic use; liver diseases, alcoholic/blood; alcoholism/blood; alcohol drinking/blood; prostatic hyperplasia/diagnosis; prostatic neoplasms/diagnosis; infection/blood; breast neoplasms/blood; breast diseases/blood; adult; child; tumor markers, biological/blood; biological markers/blood; chromatography, high pressure liquid; chromatography, ion exchange; calibration; reference values ACKNOWLEDGEMENTS This work was carried out in the Department of Clinical Chemistry, Kuopio University Hospital. I am grateful to my principal supervisor Professor Kari Punnonen, M.D., Head of the Department of Clinical Chemistry, for providing excellent research facilities and for his professional expertise and guidance during the work. I am very thankful to Professor Matti Eskelinen, M.D., my supervisor in the Department of Surgery, for introducing me to the field of research on tumour markers. I wish to express my sincere thanks to Professor (emeritus) Ilkka Penttilä, M.D., for his personal support and advice during this work. I wish to thank Professor Ilkka Mononen, M.D., for his input as an originator of this study and guidance in the early phases of this thesis. Docent C.J. Peter Eriksson, Ph.D., and Associate Professor Kari Pulkki, M.D., the official reviewers of this thesis, are gratefully acknowledged for their constructive criticism and valuable suggestions and comments for the improvement of this thesis. I owe my sincere thanks to Professor Onni Niemelä. M.D., for his fruitful collaboration. I am greatly indebted to all my co-authors, Petra Anttila, M.Sc., Joan Blake, M.Sc., Terhi Haapalainen, M.D., Toivo Halonen, Ph.D., Markku Heikinheimo, M.D., Tuula Jakobsson, M.Sc., Jari Petäjä, M.D., Eeva-Liisa Romppanen, Ph.D., and Sari Tikanoja, Ph.D. I would also like to thank all my colleagues and the personnel in the Department of Clinical Chemistry for their support during this work. For financial support, I wish to thank EVO funding of Kuopio University Hospital. I am deeply grateful to my parents Marja-Leena and Helge Romppanen for support and encouragement during my life. I wish also thank to my relatives and friends for switching my thoughts away from science. Finally, I want to express my deepest thanks to my wife Eeva-Liisa and to our lovely children, Iiro, Ella, and Henni, for their love and support. Without you, this work would never have been completed. I dedicate this thesis to you.