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

Maria A. Dikovskaya
Maria A. Dikovskaya
, 
Galina S. Russkikh
Galina S. Russkikh
, 
Konstantin V. Loktev
Konstantin V. Loktev
, 
Thomas P. Johnston
Thomas P. Johnston
, 
Margarita M. Gevorgyan
Margarita M. Gevorgyan
, 
Natalya P. Voronina
Natalya P. Voronina
, 
Valery V. Chernykh
Valery V. Chernykh
, 
Alexander N. Trunov
Alexander N. Trunov
 et 
Tatiana A. Korolenko
Tatiana A. Korolenko
   | 22 déc. 2021
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Article Category: Research Article
Publié en ligne: 22 déc. 2021
Pages: 83 - 91
Reçu: 16 août 2021
Accepté: 21 oct. 2021
DOI: https://doi.org/10.2478/raon-2021-0049
© 2022 Maria A. Dikovskaya, Galina S. Russkikh, Konstantin V. Loktev, Thomas P. Johnston, Margarita M. Gevorgyan, Natalya P. Voronina, Valery V. Chernykh, Alexander N. Trunov, Tatiana A. Korolenko, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Ocular fundus of a normal eye, and eye with choroidal melanoma. (A) Ocular fundus. Normal healthy eye (left) versus eye with choroidal melanoma (right; dia = 8 mm and thickness = 2.4 mm). (B) Ultrasound image of the choroidal melanoma (thickness = 3.1 mm).
Ocular fundus of a normal eye, and eye with choroidal melanoma. (A) Ocular fundus. Normal healthy eye (left) versus eye with choroidal melanoma (right; dia = 8 mm and thickness = 2.4 mm). (B) Ultrasound image of the choroidal melanoma (thickness = 3.1 mm).

Figure 2

Cystatin C concentration in various biological matrices in healthy individuals. Concentration of cystatin C in each biological fluid (mean ± standard deviation [s.d.]; n = 28 [n = 13 healthy controls ≤ 40 years old + n = 15 healthy controls 41–60 years old]), since Table 1 shows a significant increase in cystatin C concentrations in serum and intraocular fluid (IOF) in 61–80 year old healthy controls, and thus, this age group was not included; cerebral spinal fluid (CSF) was obtained from an additional and separate group of cancer-free neurosurgical patients (n = 8) for the determination of the cystatin C concentration as described in the Materials and methods section. a Significant difference (p < 0.001) from mean values indicated with the same letter. b Significant difference (p < 0.001) from mean values indicated with the same letter. c Significant difference (p < 0.01) from mean values indicated with the same letter. d Significant difference (p < 0.01) from mean values indicated with the same letter. e Significant difference (p < 0.01) from the mean value indicated with the same letter.
Cystatin C concentration in various biological matrices in healthy individuals. Concentration of cystatin C in each biological fluid (mean ± standard deviation [s.d.]; n = 28 [n = 13 healthy controls ≤ 40 years old + n = 15 healthy controls 41–60 years old]), since Table 1 shows a significant increase in cystatin C concentrations in serum and intraocular fluid (IOF) in 61–80 year old healthy controls, and thus, this age group was not included; cerebral spinal fluid (CSF) was obtained from an additional and separate group of cancer-free neurosurgical patients (n = 8) for the determination of the cystatin C concentration as described in the Materials and methods section. a Significant difference (p < 0.001) from mean values indicated with the same letter. b Significant difference (p < 0.001) from mean values indicated with the same letter. c Significant difference (p < 0.01) from mean values indicated with the same letter. d Significant difference (p < 0.01) from mean values indicated with the same letter. e Significant difference (p < 0.01) from the mean value indicated with the same letter.

Figure 3

Cystatin SN concentration in various biological matrices in healthy individuals. Concentration of cystatin SN in each biological fluid (mean ± standard deviation [s.d.]; n = 28 [n = 13 healthy controls ≤ 40 years old + n = 15 healthy controls 41–60 years old]), since Table 1 shows a significant increase in the cystatin SN concentration in the serum of 61–80 year old healthy controls, and thus, this age group was not included; cerebral spinal fluid (CSF) was obtained from an additional and separate group of cancer-free neurosurgical patients (n = 8) for the determination of the cystatin SN concentration as described in the Materials and methods section. a Significant difference (p < 0.001) from the mean value indicated with the same letter. b Significant difference (p < 0.05) from mean values indicated with the same letter. c Significant difference (p < 0.001) from the mean value indicated with the same letter. d Significant difference (p < 0.01) from the mean value indicated with the same letter. e Significant difference (p < 0.001) from the mean value indicated with the same letter.
Cystatin SN concentration in various biological matrices in healthy individuals. Concentration of cystatin SN in each biological fluid (mean ± standard deviation [s.d.]; n = 28 [n = 13 healthy controls ≤ 40 years old + n = 15 healthy controls 41–60 years old]), since Table 1 shows a significant increase in the cystatin SN concentration in the serum of 61–80 year old healthy controls, and thus, this age group was not included; cerebral spinal fluid (CSF) was obtained from an additional and separate group of cancer-free neurosurgical patients (n = 8) for the determination of the cystatin SN concentration as described in the Materials and methods section. a Significant difference (p < 0.001) from the mean value indicated with the same letter. b Significant difference (p < 0.05) from mean values indicated with the same letter. c Significant difference (p < 0.001) from the mean value indicated with the same letter. d Significant difference (p < 0.01) from the mean value indicated with the same letter. e Significant difference (p < 0.001) from the mean value indicated with the same letter.

Figure 4

Cystatin C (A) and cystatin SN (B) concentrations and their ratio (C) in the serum and tear fluid of patients with uveal melanoma. (A) Values represent the mean ± standard deviation (s.d.) of n = 15 healthy controls (mean age = 53.1 ± 3.4 years) and n = 51 of 57 total patients with uveal melanoma (mean age = 51.7 ± 2.8 years; 6 patients were > 60 years old and were therefore not included). (B) Values represent the mean ± s.d. of n = 15 healthy controls (mean age = 53.1 ± 3.4 years) and n = 51 of 57 total patients with uveal melanoma (mean age = 51.7 ± 2.8 years; 6 patients were > 60 years old and were therefore not included). (C) Values represent the mean ± s.d. of n = 15 healthy controls (mean age = 53.1 ± 3.4 years) and n = 51 of 57 total patients with uveal melanoma (mean age = 51.7 ± 2.8 years; 6 patients were > 60 years old and were therefore not included). * = significant difference (p < 0.001) from the mean value for healthy controls in each biological matrix
Cystatin C (A) and cystatin SN (B) concentrations and their ratio (C) in the serum and tear fluid of patients with uveal melanoma. (A) Values represent the mean ± standard deviation (s.d.) of n = 15 healthy controls (mean age = 53.1 ± 3.4 years) and n = 51 of 57 total patients with uveal melanoma (mean age = 51.7 ± 2.8 years; 6 patients were > 60 years old and were therefore not included). (B) Values represent the mean ± s.d. of n = 15 healthy controls (mean age = 53.1 ± 3.4 years) and n = 51 of 57 total patients with uveal melanoma (mean age = 51.7 ± 2.8 years; 6 patients were > 60 years old and were therefore not included). (C) Values represent the mean ± s.d. of n = 15 healthy controls (mean age = 53.1 ± 3.4 years) and n = 51 of 57 total patients with uveal melanoma (mean age = 51.7 ± 2.8 years; 6 patients were > 60 years old and were therefore not included). * = significant difference (p < 0.001) from the mean value for healthy controls in each biological matrix

Figure 5

Concentration of cystatin C (A) and cystatin SN (B) in intraocular fluid of patients with uveal melanoma versus healthy controls. (A) Values represent the mean ± standard deviation (s.d.) of n = 7 healthy controls (mean age = 57.5 ± 1.9 years) and n = 18 of 57 total uveal melanoma patients selected based on an age close to the mean age of the 7 healthy controls (mean age = 55.9 ± 3.2 years; n = 18). (B) Values represent the mean ± s.d. of n = 7 healthy controls (mean age = 57.5 ± 1.9 years) and n = 18 of 57 total uveal melanoma patients selected based on an age close to the mean age of the 7 healthy controls (mean age = 55.9 ± 3.2 years; n = 18). * = significant difference (p < 0.001) from mean value for healthy controls; IOF = intraocular fluid
Concentration of cystatin C (A) and cystatin SN (B) in intraocular fluid of patients with uveal melanoma versus healthy controls. (A) Values represent the mean ± standard deviation (s.d.) of n = 7 healthy controls (mean age = 57.5 ± 1.9 years) and n = 18 of 57 total uveal melanoma patients selected based on an age close to the mean age of the 7 healthy controls (mean age = 55.9 ± 3.2 years; n = 18). (B) Values represent the mean ± s.d. of n = 7 healthy controls (mean age = 57.5 ± 1.9 years) and n = 18 of 57 total uveal melanoma patients selected based on an age close to the mean age of the 7 healthy controls (mean age = 55.9 ± 3.2 years; n = 18). * = significant difference (p < 0.001) from mean value for healthy controls; IOF = intraocular fluid

Concentrations of cystatin C and cystatin SN in biological fluids of healthy individuals as a function of age (Mean ± s.d.)

Groups Inhibitor Serum (ng/mL) Tears (ng/mL) IOF (ng/mL)
Healthy Cystatin C 561 ± 10.0 296 ± 11.1 -
(≤ 40 years) [n = 13] Cystatin SN 2.24 ± 0.20 0.49 ± 0.30
Healthy Cystatin C 539 ± 111 256 ± 82.3 414 ± 28
(41–60 years) [n = 15] Cystatin SN 2.96 ± 0.70 0.6 ± 0.35 2.7 ± 1.40
Healthy Cystatin C a1,341 ± 177 382 ± 116 a844 ± 113
(61–80 years) [n = 9] Cystatin SN b4.77 ± 0.10 0.75 ± 0.14 2.18 ± 0.20
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