Aberrant cystatin‑C expression in blood from patients with breast cancer is a suitable marker for monitoring tumor burden
Open accessAbstract
The present study was performed to evaluate the efficacy of circulating cystatin-C as a tumor monitoring biomarker at different clinical time points in patients with breast cancer over a long-term follow-up period. In addition, the secretory rate of circulating cystatin-C from cancer tissue was investigated by comparing the blood and tissue expression levels of cystatin-C. Blood samples from healthy volunteers (40 males and 40 females) were obtained at yearly health examinations if laboratory and imaging abnormalities were not detected. Blood samples from 34 patients with breast cancer were obtained at 205 different time points of clinical progression. Blood levels of cystatin-C were measured using ELISA and the tissue levels were measured using immunohistochemistry. No age-associated effect was observed in male and female blood cystatin-C levels. The positivity rate was 46% in patients (38/83) and 40% in samples collected at different time points (82/205). Blood cystatin-C levels were lowest following surgery compared with patients with systemic metastasis (P<0.001). The sensitivity, specificity and accuracy rates of ELISA were 53.6, 63.6 and 53.9%, respectively. The concordance rate between blood and tissue expression was 38%. The main reason for discordance between tissue and serum expression of cytostatin-C came from low serum positivity in samples showing tissue cytostatin-C (3/11, 27%). The specificity between cytostatin-C and CA-125 was highest in tumor absence state. In conclusion, elevated blood levels of cystatin-C were observed in 40% of breast cancer cases and were tumor-volume dependent. However, the concordance rate between tissue and blood was quite low, suggesting tumor heterogeneity of cystatin-C expression or co-acting pathway activation, such as cathepsin D. As one-third of breast cancer tissues express cystatin-C without cancer antigen 15-3 elevation, cystatin-C may represent a good tumor-monitoring marker in breast cancer.
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The association between CyC-production PGSs and reduced lifespan is consistent with evidence for elevated plasma CyC in patients with cancer.
“and is consistent with evidence for elevated plasma CyC in patients with cancer.14”
From Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy (2023) · cites this paper as [14]
The Results report higher blood cystatin-C levels in patients with breast cancer than in healthy female volunteers (P=0.034), supporting evidence of elevated circulating CyC in cancer. The paper describes blood and serum measurements, however, not a plasma measurement; its own comparison is specifically in breast cancer. (LLM, conf=0.82)
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- Authors
- Kwon, W., Kim, T., Nahm, C., Moon, Y., & Kim, J.
- Affiliations
- Yonsei University (KR)
- Inha University (KR)
- Corresponding author
- Kim, Jin
- Venue
- Oncology Letters
- Publisher
- Spandidos Publications
- Published
- 2018-09-03
- Volume
- 16
- Issue
- 5
- Pages
- 5583-5590
- ISSN
- 1792-1074 (ISSN-L)
- 1792-1082
- PMC
- PMC6176264
- OpenAlex
- W2889176828
- Cited by
- 21
- References
- 30
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 1
- FWCI
- 0.45
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Oncology Letters (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Keywords
- cystatin C, breast cancer, circulating tumor markers, tumor burden monitoring, tumor heterogeneity, cathepsin D, CA125, metastasis, tumor volume
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