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The SLC25A45-TML Axis as a Biological Foundation for a Multivariable Plasma Metabolite Signature for High-Precision Prostate Cancer Detection
by
, , and
Liang Zhao
1,*
,
Raghothama Chaerkady
1,
Naseruddin Höti
1,
Eric Zhao
2,
Anirudh Kashyap
1,
Morgan Fair
1,
Qing Wang
1,3,*
and
Xiaonan Kang
4,* 1
Complete Omics Inc., Baltimore, MD 21227, USA
2
Gilman School, Baltimore, MD 21210, USA
3
Complete Omics (Hangzhou) Inc., Hangzhou 311200, China
4
Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
*
Authors to whom correspondence should be addressed.
Cancers 2026, 18(10), 1571; https://doi.org/10.3390/cancers18101571
Submission received: 17 March 2026
/
Revised: 2 May 2026
/
Accepted: 9 May 2026
/
Published: 12 May 2026
(This article belongs to the Collection Biomarkers for Detection and Prognosis of Prostate Cancer)
Simple Summary
Current blood tests for prostate cancer (PCa), such as the standard primarily prostate-specific antigen (PSA) screen, often lack the specificity needed to accurately detect the disease, frequently leading to overdiagnosis and unnecessary biopsies. To address this clinical challenge, we utilized a highly sensitive analytical platform, Complete360®-MyMeta, to search for new, more reliable chemical markers in patient blood. Our findings indicate that as prostate tumors grow, they act as a localized “metabolic sink”, actively pulling specific circulating nutrients—particularly trimethyllysine (TML) and polyamine precursors—out of the bloodstream to fuel their massive energy demands. By simultaneously measuring the depletion of these circulating nutrients and the elevation of their metabolic byproducts, we developed a new diagnostic signature based on mathematical ratios. In our initial discovery cohort, this ratio-based approach successfully minimized natural physiological background noise, achieving highly accurate detection of prostate cancer across all clinical stages. Ultimately, this work provides a strong biological foundation for a new, non-invasive “liquid biopsy”. Pending confirmation in larger clinical trials, this mechanistically grounded test could significantly improve early detection and reduce the burden of unnecessary medical procedures for patients.
Abstract
Background: Prostate cancer remains a significant global health burden, yet current diagnostic reliance on PSA screening is heavily hampered by limited specificity and high rates of overdiagnosis. Methods: To address this clinical bottleneck, we utilized a highly sensitive Complete360®-MyMeta targeted-metabolomics platform to perform high-resolution profiling of 43 metabolites across the carnitine, polyamine, and methylation networks in plasma from a discovery cohort of all-stage (I–IV) PCa patients and healthy controls. Results: Our analysis identified 28 significantly altered metabolites (p < 0.05), revealing profound systemic metabolic reprogramming characterized by the depletion of circulating TML and putrescine, alongside the elevation of L-acetylcarnitine and sarcosine. These systemic shifts are consistent with a localized tumoral “metabolic sink”, wherein upregulated mitochondrial TML import via the SLC25A45 transporter actively fuels fatty acid oxidation, while parallel androgen signaling drives massive polyamine synthesis. Translating these mechanistic insights into a clinical tool, we developed a multivariable diagnostic signature utilizing mathematically stable bipartite metabolic ratios. An optimized, cross-validated model combining L-acetylcarnitine/TML and sarcosine/putrescine effectively mitigated physiological noise to achieve robust diagnostic separation, yielding an area under the curve (AUC) of 0.99. Conclusions: Ultimately, this study provides a discovery-phase proof-of-concept for the SLC25A45-TML axis as a mechanistically grounded, stage-independent liquid biopsy, offering a rational, non-invasive framework to significantly improve PCa detection.
