Discovery of Metabolic Biomarkers for Triple Negative Breast Cancer in Asian Female Population

Triple negative breast cancer (TNBC) is a devastating cancer disease characterized by its poor prognosis and aggressive biological behavior. In this work, we applied state-of-the-art metabolomics technology to discover metabolic signatures in Asian female TNBC patients.

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Breast cancer (BC) is a challenging health problem for women and healthcare providers globally. Among the different types of BC, triple negative breast cancer (TNBC) accounts for a small percentage (10-20%). However, it is amongst the most highly aggressive cancers and has a poorer prognosis than most. The outcome of TNBC is impacted by race/ethnicity – Asian TNBC patients present more commonly with large invasive tumors, high node positivity, and high histologic grade. So far, few studies have been conducted to understand the metabolic changes associated with TNBC in the Asian population and there are no biomarkers available to predict its prognostic consequences. Our untargeted metabolomics work presents a snapshot of blood metabolic differences between TNBC patients and healthy women, showing that unique metabolic features in the blood of Asian TNBC patients can be used to predict their five-year survival rate (Scientific Reports, 2019, DOI: 10.1038/s41598-019-57068-5). This work will facilitate the development of better treatment strategies to combat TNBC within the Asian population and hopefully advance new avenues for the development of personalized medicine for TNBC patients. 

This work is an international collaboration between Chongqing University Cancer Hospital (Chongqing, China) and the University of British Columbia (Vancouver, Canada). As the top-ranked hospital in Chongqing (one of the largest metropolitan cities in southwest China), Chongqing University Cancer Hospital receives over 1,000 new cases of breast cancer every year. Among these BC patients, 15% are diagnosed with TNBC. "The economic burden is large, there are no well-established diagnostic tools, and if available, they are expensive for the family," say co-authors Professor Weiqi Nian and Professor Xiaodong Zheng, who are the specialists in TNBC working in Chongqing University Cancer Hospital. Although Asian TNBC patients face a poorer prognosis, few studies have been documented in Asians, with most published TNBC studies having been conducted with Western populations,. Therefore, no biomarkers have been identified to guide the treatment of TNBC and predict consequences for Asian TNBC patients. 

Motivated to address this knowledge gap, Dr. Lixian Li initiated the collection of serum samples from TNBC patients in southwest China beginning in 2013 and performed detailed follow-ups with TNBC cases for at least 5 years or until patients passed away. In total, 150 individuals were monitored and 31 of them were used in this study. In addition, serum samples from healthy, age-matched female volunteers were collected. Untargeted metabolomics was performed using ultrahigh performance liquid chromatography–high resolution mass spectrometry (UHPLC-MS). Further statistical analysis was performed to correlate metabolomic information with patients’ 5-year survival rate to discover six metabolites, including uridine monophosphate, octanoylcarnitine, proline, lysophosphatidylcholine (22:1), phosphatidylserine (20:0/0:0), and uric acid, all of which show excellent diagnostic capabilities (AUC > 0.75). Overall, this work presents the first metabolomics study of TNBC in an Asian population, providing a comprehensive understanding of metabolic dysregulations of TNBC in the Asian female population. The in-depth metabolic information from this study has the potential to accelerate the development of novel therapeutic strategies and better TNBC treatments.

The reported study is only the beginning of our endeavor in better understanding TNBC in the Asian population. Based on the metabolic signatures found in this study, our next step is to develop a robust, sensitive, and cost-effective assay for use in real clinical settings. To achieve this goal, we are in the process of large scale collection of biological samples from several hospitals to validate our discoveries in order to apply it to clinical settings. Our ultimate goal is to develop a strategy to predict TNBC at its early stages to improve patient outcomes of this highly devastating disease.  

Written by Lixian Li [1, 2], Nathaniel Villanueva [2] and Tao Huan [2]

1 Chongqing University Cancer Hospital, Chongqing, 400030, P.R. China.
2 Department of Chemistry, University of British Columbia, Vancouver, British Columbia, V6T 1Z1, Canada

Tao Huan

Assistant Professor, University of British Columbia