The potential of cystatin C as a predictive biomarker in breast cancer

Leto, Gaetano; Sepporta, Maria Vittoria

doi:10.1080/14737140.2020.1829481

“…For example, elevated expression of cathepsin cysteine peptidases and subsequent unregulated proteolysis has been implicated in a range of cancers [34]. The malignant progression of the cancerous cells and tumour formation is exacerbated by reduced levels of the endogenous inhibitors used to regulate the cathepsin peptidases, such as cystatin C that regulates cathepsin B in cases of tongue cancer [35] and breast cancer [36]. Moreover, decreased levels of Stefin A and Stefin B are associated with breast, prostate, cervical and brain cancers [37][38][39][40].…”

Section: Discussionmentioning

confidence: 99%

Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth Fasciola hepatica

Cwiklinski

¹

,

Drysdale

²

,

Corrales

³

et al. 2022

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The liver fluke Fasciola hepatica is an economically important global pathogen of humans and their livestock. To facilitate host invasion and migration, F. hepatica secretes an abundance of cathepsin peptidases but prevents excessive damage to both parasite and host tissues by co-secreting regulatory peptidase inhibitors, cystatins/stefins and Kunitz-type inhibitors. Here, we report a vaccine strategy aimed at disrupting the parasite’s protease/anti-protease balance by targeting these key inhibitors. Our vaccine cocktail containing three recombinant stefins (rFhStf-1, rFhStf-2, rFhStf-3) and a Kunitz-type inhibitor (rFhKT1) formulated in adjuvant Montanide 61VG was assessed in two independent sheep trials. While fluke burden was not reduced in either trial, in Trial 1 the vaccinated animals showed significantly greater weight gain (p < 0.05) relative to the non-vaccinated control group. In both trials we observed a significant reduction in egg viability (36–42%). Multivariate regression analyses showed vaccination and increased levels of IgG2 antibodies specific for the F. hepatica peptidase inhibitors were positive indicators for increased weight gain and levels of haemoglobin within the normal range at 16 weeks post-infection (wpi; p < 0.05). These studies point to the potential of targeting peptidase inhibitors as vaccine cocktails for fasciolosis control in sheep.

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“…have recently reported that both serum and urine cystatin C levels are elevated, and the cystatin C gene is upregulated nearly 50-fold, in patients with multiple myeloma, which suggests it use as a diagnostic biomarker in multiple myeloma. 31 Additionally, Leto and Sepporta 32 suggested the use of cystatin C as a predictive biomarker for breast cancer. Lastly, it is worth noting that Kos et al .…”

Section: Discussionmentioning

confidence: 99%

“…The precise role of cysteine protease inhibitors in the development of eye tumors has not been fully elucidated to date. 30 , 31 , 32 This is significant to ophthalmology, because some of these inhibitors may be of therapeutic benefit for the treatment of eye tumors. Thus, the aim of this study was to investigate the concentration of endogenous inhibitors of cysteine proteases; namely, cystatin C and cystatin SN, in the serum and the biological fluids of the eye in both healthy controls and patients with uveal melanoma.…”

Section: Introductionmentioning

confidence: 99%

Cystatin C and cystatin SN as possible soluble tumor markers in malignant uveal melanoma

Dikovskaya

¹

,

Русских

²

,

Loktev

³

et al. 2021

Radiology and Oncology

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Background The aim of the study was to determine the concentration of endogenous cystatin C and cystatin SN, as potential tumor biomarkers, in the serum and biological fluids of the eye in both healthy controls and patients with uveal melanoma. Patients and methods The concentration of both cystatins was determined in the intraocular fluid (IOF), tear fluid, and serum of patients with uveal melanoma and compared to baseline measurements in IOF, tears, serum, cerebral spinal fluid, saliva and urine of healthy controls. Results The concentration of cystatin C in all the biological matrices obtained from healthy controls significantly exceeded the concentration of cystatin SN and was independent of gender. Cystatin C concentrations in the tear fluid of patients with uveal melanoma (both the eye with the malignancy, as well as the contralateral, non-affected eye), were significantly greater than cystatin C concentrations in the tear fluid of healthy controls and was independent of tumor size. The concentration of cystatin SN in IOF of patients with uveal melanoma was significantly less than the corresponding concentration of cystatin SN in healthy controls. Conclusions The ratio of cystatins (CysC:CysSN) in both the serum and tear fluid, as well as the concentration of cystatin SN in IOF, would appear to strongly suggest the presence of uveal melanoma. It is further suggested that multiple diagnostic criteria be utilized if a patient is suspected of having uveal melanoma, such as determination of the cystatin C and cystatin SN concentrations in serum, tears, and IOF, ocular fundus and ultrasound imaging, and biopsy with histopathological evaluation.

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“…Due to these properties, even very small changes in the glomerular filtration rate (GFR) may significantly alter serum CysC level, potentially making this basic protein a very sensitive marker of renal filtration [ 7 ]. Since it was first described in 1961 by Jorgen Clausen in human cerebrospinal fluid [ 8 ], CysC has been thoroughly investigated and is considered a promising biomarker for several diseases, including but not limited to kidney disease and nephropathy-related diabetes [ 9 , 10 ], Alzheimer's disease [ 11 ], and breast cancer [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Association between Cystatin C and Cardiac Function in Acute Myocardial Infarction Patients: A Real-World Analysis

Lou

¹

,

Luo

²

,

Zhang

³

et al. 2022

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Background. Acute myocardial infarction (AMI), as well as its long-term and short-term complications, is known to present with high morbidity and mortality. Cardiac function deterioration and ventricular remodelling after AMI are known to be correlated to worse long-term outcomes. However, the underlying mechanism remains elusive and there is a shortage of serum prediction markers. This study investigates the relationship between in-hospital Cystatin C (CysC) and cardiac function and subsequent prognosis among AMI patients. Research Design and Methods. We measured admission CysC and cardiac function parameters, including ejection fraction (EF) and pro-BNP value in 5956 patients diagnosed with AMI. Simple and multiregression analyses were performed to investigate the correlation between CysC and cardiac function in AMI patients. Major adverse cardiovascular events (MACE), cardiovascular, and all-cause mortality were documented, and 351 participants with high cystatin (≥1.09 mg/L) and 714 low cystatin (<1.09 mg/L) were investigated for survival analysis during a 48-month follow-up. Results. 5956 patients with AMI were enrolled in the initial observational analysis, and 1065 patients of the whole cohort were included in the follow-up survival analysis. The admission CysC level was found to be significantly positively correlated to the pro-BNP level ( R square = 0.2142 , 95% CI 4758 to 5265, p < 0.0001 ) and negatively correlated to the EF value ( R square = 0.0095 , 95% CI -3.503 to -1.605, p < 0.0001 ). Kaplan-Meier survival analysis revealed significantly increased MACE incidence ( HR = 2.293 , 95% CI 1.400 to 3.755, p < 0.0001 ), cardiovascular mortality ( HR = 3.016 , 95% CI 1.694 to 5.371, p = 0.0002 ), and all-cause mortality ( HR = 3.424 , 95% CI 2.010 to 5.835, p < 0.0001 ) in high-admission CysC cohort with AMI at the end of 4-year follow-up. Conclusions. Admission CysC is negatively correlated with cardiac function in AMI patients and acts as a novel predictor for MACE incidence in the whole population. Further studies are needed to investigate the specific mechanism of CysC in the cardiac function deterioration among AMI patients.

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The potential of cystatin C as a predictive biomarker in breast cancer

Cited by 11 publications

References 79 publications

Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth Fasciola hepatica

Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth Fasciola hepatica

Cystatin C and cystatin SN as possible soluble tumor markers in malignant uveal melanoma

Association between Cystatin C and Cardiac Function in Acute Myocardial Infarction Patients: A Real-World Analysis

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