Doctoral Defence in Health Sciences – Kristrún Ýr Holm

On Thursday, 3 September, Kristrún Ýr Holm will defend her doctoral thesis in Health Sciences at the Faculty of Pharmaceutical Sciences at the University of Iceland. The thesis is entitled: “Search for novel biomarkers in human plasma for breast cancer diagnosis.”

The opponents are Dr. John R. Yates III, Professor at The Scripps Research Institute, and Dr. Julia Debik, Associate Professor at NTNU (Norwegian University of Science and Technology).

The principal supervisor was Margrét Þorsteinsdóttir, Professor, and the supervisor was Sigríður Klara Böðvarsdóttir, Professor and Head of Department. In addition, the doctoral committee comprised Margrét Helga Ögmundsdóttir, Professor; Óttar Rolfsson, Professor; Stefán Sigurðsson, Professor; and Zoltan Takats, Professor.

Berglind Eva Benediktsdóttir, Associate Professor and Dean of the Faculty of Pharmaceutical Sciences, will chair the ceremony, which will take place in Hátíðasalur in the University of Iceland and begin at 1:00 p.m.

Abstract

Breast cancer is the most common cancer among women worldwide and is a heterogeneous disease in which early detection is critical for improving survival. Blood-based biomarkers may offer a minimally invasive approach to complement current screening methods and improve early detection. For this to become a reality, robust analytical methods for the identification and quantification of breast cancer biomarkers need to be developed.

The objectives of this study were to optimize and automate sample preparation for targeted protein quantification to support its use in clinical research and to identify plasma biomarkers with diagnostic and prognostic value for breast cancer. Targeted protein quantification was performed using ultra-performance liquid chromatography multiple reaction monitoring mass spectrometry (UPLC-MRM-MS), and a comprehensive metabolomic profiling was conducted using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF) and nuclear magnetic resonance (NMR). These analyses were applied to plasma samples from a well-characterized Icelandic breast cancer cohort.

Sample preparation for targeted protein quantification was successfully optimized and shortened. Of 98 quantified proteins, eight were associated with breast cancer subtypes, BRCA1/2 mutation status, and aggressive tumor characteristics. Three of these proteins were associated with reduced breast cancer-specific survival. Comprehensive metabolomic analysis revealed breast cancer-specific metabolic alterations in plasma and indicated subgroup-specific metabolite signatures that may reflect cancer-related shifts in glycolysis, fatty acid metabolism, and amino acid metabolism. These findings suggest that plasma protein and metabolomic signatures can provide insights into breast cancer-associated molecular alterations and support biomarker discovery. Furthermore, the findings highlight the importance of considering breast cancer heterogeneity in the search for novel circulating biomarkers.

About the doctoral candidate

Kristrún Ýr Holm was born in Reykjavík in 1995. She graduated from the natural sciences programme at the Commercial College of Iceland (Verzlunarskóli Íslands) in 2015, completed a B.Sc. degree in Biochemistry and Molecular Biology at the University of Iceland in 2018, and an M.Sc. degree in Life and Medical Sciences at the same university in 2020.

She began her doctoral studies at the University of Iceland in the spring semester of 2021. Alongside her studies, Kristrún Ýr has played football for Keflavík and Þróttur Reykjavík, as well as working in teaching at the University of Iceland.

Kristrún Ýr's parents are Örn Sævar Holm and Bryndís Knútsdóttir. Her spouse is Aron Ingi Steingrímsson, and their son is Aron Leó.