Serum Proteomic Profiling by SomaScan Aptamer Array Identifies Candidate Predictive and Monitoring Biomarkers of Distant Recurrence in Triple-Negative Breast Cancer
9 affiliations
- 1Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA 90069, USA
- 2Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- 3Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- 4Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, TX 78712, USA
- 5California Institute of Technology, Pasadena, CA 91125, USA
- 6Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto 6068507, Japan
- 7Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- 8Women’s Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- 9Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Abstract
Triple-negative breast cancer (TNBC) lacks a blood-based biomarker for predicting or monitoring distant recurrence. We profiled 39 serum samples from 38 women (10 healthy controls; 12 non-recurrent [NR]; eight diagnosis-timepoint samples from patients who later recurred [DR-DIG]; nine recurrence-timepoint samples [DR-REC]) using the SomaScan v5.0 aptamer platform). Public tumor-tissue transcriptomic cohorts were used for supportive and exploratory analyses. No protein reached a false discovery rate (FDR) < 0.05 for NR vs. DR-DIG; granzyme A (GZMA) and endoplasmic reticulum aminopeptidase 1 (ERAP1) showed the strongest nominal signals. For DR-DIG vs. DR-REC, 38 aptamers (37 proteins) reached FDR < 0.05, enriched for RNA-binding and nuclear-envelope proteins; this signature was retained in leave-one-out and storage-adjusted analyses. Higher GZMA mRNA was associated with longer recurrence-free survival in two independent cohorts (hazard ratio [HR] = 0.795, p = 0.018; HR = 0.186, p = 0.0057). Monitor genes showed near-chance concordance with metastatic tissue, and the source of the signature could not be resolved. An exploratory four-gene elastic-net panel reached a concordance index of 0.613 internally but 0.559 externally. GZMA is a candidate serum biomarker of TNBC recurrence risk, and the monitor signature is a preliminary observation. Both require protein-level validation in independent, prospectively collected serum cohorts.
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BibTeX
@article{kim2026serum,
title = {{Serum Proteomic Profiling by SomaScan Aptamer Array Identifies Candidate Predictive and Monitoring Biomarkers of Distant Recurrence in Triple-Negative Breast Cancer}},
author = {Jina Kim and Sunao Tanaka and Edwardia Fosah and Cynthia Jinno and Hyoyoung Kim and Thanosan Prathifkumar and Yukiko Fukui and Kana Kawanishi and Masahiro Kawashima and Norikazu Masuda and Joshua Levy and Takeo Fujii and Sungyong You and Hideki Furuya},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209070},
url = {https://www.mdpi.com/1422-0067/27/20/9070},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Serum Proteomic Profiling by SomaScan Aptamer Array Identifies Candidate Predictive and Monitoring Biomarkers of Distant Recurrence in Triple-Negative Breast Cancer
AU - Jina Kim
AU - Sunao Tanaka
AU - Edwardia Fosah
AU - Cynthia Jinno
AU - Hyoyoung Kim
AU - Thanosan Prathifkumar
AU - Yukiko Fukui
AU - Kana Kawanishi
AU - Masahiro Kawashima
AU - Norikazu Masuda
AU - Joshua Levy
AU - Takeo Fujii
AU - Sungyong You
AU - Hideki Furuya
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209070
UR - https://www.mdpi.com/1422-0067/27/20/9070
AB - Triple-negative breast cancer (TNBC) lacks a blood-based biomarker for predicting or monitoring distant recurrence. We profiled 39 serum samples from 38 women (10 healthy controls; 12 non-recurrent [NR]; eight diagnosis-timepoint samples from patients who later recurred [DR-DIG]; nine recurrence-timepoint samples [DR-REC]) using the SomaScan v5.0 aptamer platform). Public tumor-tissue transcriptomic cohorts were used for supportive and exploratory analyses. No protein reached a false discovery rate (FDR) < 0.05 for NR vs. DR-DIG; granzyme A (GZMA) and endoplasmic reticulum aminopeptidase 1 (ERAP1) showed the strongest nominal signals. For DR-DIG vs. DR-REC, 38 aptamers (37 proteins) reached FDR < 0.05, enriched for RNA-binding and nuclear-envelope proteins; this signature was retained in leave-one-out and storage-adjusted analyses. Higher GZMA mRNA was associated with longer recurrence-free survival in two independent cohorts (hazard ratio [HR] = 0.795, p = 0.018; HR = 0.186, p = 0.0057). Monitor genes showed near-chance concordance with metastatic tissue, and the source of the signature could not be resolved. An exploratory four-gene elastic-net panel reached a concordance index of 0.613 internally but 0.559 externally. GZMA is a candidate serum biomarker of TNBC recurrence risk, and the monitor signature is a preliminary observation. Both require protein-level validation in independent, prospectively collected serum cohorts.
SN - 1422-0067
ER -