A Computational Statistics Approach to Evaluate Blood Biomarkers for Breast Cancer Risk Stratification.

Content Provider	Europe PMC
Author	Oktay, Kaan Santaliz-Casiano, Ashlie Patel, Meera Marino, Natascia Storniolo, Anna Maria V. Torun, Hamdi Acar, Burak Madak Erdogan, Zeynep
Abstract	Breast cancer is the second leading cause of cancer mortality among women. Mammography and tumor biopsy followed by histopathological analysis are the current methods to diagnose breast cancer. Mammography does not detect all breast tumor subtypes, especially those that arise in younger women or women with dense breast tissue, and are more aggressive. There is an urgent need to find circulating prognostic molecules and liquid biopsy methods for breast cancer diagnosis and reducing the mortality rate. In this study, we systematically evaluated metabolites and proteins in blood to develop a pipeline to identify potential circulating biomarkers for breast cancer risk. Our aim is to identify a group of molecules to be used in the design of portable and low-cost biomarker detection devices. We obtained plasma samples from women who are cancer free (healthy) and women who were cancer free at the time of blood collection but developed breast cancer later (susceptible). We extracted potential prognostic biomarkers for breast cancer risk from plasma metabolomics and proteomics data using statistical and discriminative power analyses. We pre-processed the data to ensure the quality of subsequent analyses, and used two main feature selection methods to determine the importance of each molecule. After further feature elimination based on pairwise dependencies, we measured the performance of logistic regression classifier on the remaining molecules and compared their biological relevance. We identified six signatures that predicted breast cancer risk with different specificity and selectivity. The best performing signature had 13 factors. We validated the difference in level of one of the biomarkers, SCF/KITLG, in plasma from healthy and susceptible individuals. These biomarkers will be used to develop low-cost liquid biopsy methods toward early identification of breast cancer risk and hence decreased mortality. Our findings provide the knowledge basis needed to proceed in this direction.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC10355241&blobtype=pdf
ISSN	18688497
Volume Number	11
DOI	10.1007/s12672-019-00372-3
PubMed Central reference number	PMC10355241
Issue Number	1
PubMed reference number	31858384
Journal	Hormones & Cancer [Horm Cancer]
e-ISSN	18688500
Language	English
Publisher	Springer US
Publisher Date	2019-12-19
Publisher Place	New York
Access Restriction	Open
Rights License	© Springer Science+Business Media, LLC, part of Springer Nature 2019
Subject Keyword	Liquid biopsy Breast cancer risk Circulating biomarker Machine learning Feature selection
Content Type	Text
Resource Type	Article
Subject	Medicine