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Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases

Katja Goricar
Katja Goricar
, 
Viljem Kovac
Viljem Kovac
, 
Metoda Dodic-Fikfak
Metoda Dodic-Fikfak
, 
Vita Dolzan
Vita Dolzan
 and 
Alenka Franko
Alenka Franko
   | Mar 07, 2020
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Article Category: research article
Published Online: Mar 07, 2020
Page range: 86 - 95
DOI: https://doi.org/10.2478/raon-2020-0011
© 2020 Katja Goricar, Viljem Kovac, Metoda Dodic-Fikfak, Vita Dolzan, Alenka Franko, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1

Median soluble mesothelin-related peptides (SMRP) levels in different groups (A), receiver operating characteristic (ROC) curve for SMRP predicting malignant mesothelioma (MM) (B) and association of MSLN rs1057147 genotype with serum SMRP levels at inclusion in the study in the whole cohort of 698 subjects (C) and for each subject group (D). Data are presented as median with 95% confidence intervals.
Median soluble mesothelin-related peptides (SMRP) levels in different groups (A), receiver operating characteristic (ROC) curve for SMRP predicting malignant mesothelioma (MM) (B) and association of MSLN rs1057147 genotype with serum SMRP levels at inclusion in the study in the whole cohort of 698 subjects (C) and for each subject group (D). Data are presented as median with 95% confidence intervals.

Figure 2

The influence of MSLN rs1057147 genotype on overall survival (A) and receiver operating characteristic (ROC) curve for MSLN rs1057147 and soluble mesothelin-related peptides (SMRP) predicting overall survival above median (B).
The influence of MSLN rs1057147 genotype on overall survival (A) and receiver operating characteristic (ROC) curve for MSLN rs1057147 and soluble mesothelin-related peptides (SMRP) predicting overall survival above median (B).

Clinical characteristics of study groups

CharacteristicAll subjects (N =782)No disease (N = 69)Pleural plaques (N = 410)Asbestosis (N = 149)MM (N = 154)MM with SMRP at diagnosis (N = 86)
GenderMale, N (%)581 (74.3)52 (75.4)295 (72.0)115 (77.2)119 (77.3)69 (80.2)
Female, N (%)201 (25.7)17 (24.6)115 (28.0)34 (22.8)35 (22.7)17 (19.8)
AgeYears, median 25%–75%)56.9 (50.2–64.9)52.9 (48.2–59.2)54.6 (48.8–62.2)59.1 (51.2–65.2)65 (57–70)66 (59–72)
SmokingNo, N (%)375 (49.0) [17]31 (45.6) [1]203 (50.9) [11]71 (48.0) [1]70 (46.7) [4]43 (51.2) [2]
Yes, N (%)390 (51.0)37 (54.4)196 (49.1)77 (52.0)80 (53.3)41 (48.8)
SMRPnmol/l, median (25%-75%)0.30 (0.00–0.85) [1]0.14 (0.00–0.58) [6]0.03 (0.00–0.39) [5]2.43 (0.44–8.62)

Odds for MM in subjects with different MSLN rs1057147 genotypes

No diseasePleural plaquesAsbestosisMMMM vs all other subjects
Genotype(N = 69)(N = 410)(N = 149)(N = 154)
N (%)N (%)N (%)N (%)OR (95% CI)pORadj(95% CI) padj
GG41 (60.3) [1]241 (59.1) [2]84 (56.8) [1]81 (52.6)referencereference
GA21 (30.9)147 (36.0)49 (33.1)60 (39.0)1.25 (0.86–1.82)0.2431.28 (0.87–1.90)0.215
AA6 (8.8)20 (4.9)15 (10.1)13 (8.4)1.43 (0.73–2.80)0.2921.30 (0.64–2.64)0.472
GA+AA27 (39.7)167 (40.9)64 (43.2)73 (47.4)1.28 (0.90–1.82)0.1741.29 (0.89–1.87)0.187

Serum SMRP levels according to MSLN rs1057147 genotype

MSLN rs1057147MSLN rs1057147
GroupGG genotypeGA genotypeAA genotypeKruskal-Wallis test statisticpaGA+AA genotypeMann-Whitney Upb
SMRP (nmol/l, median (25%–75%)SMRP (nmol/l, median (25%–75%)SMRP (nmol/l, median (25%–75%)SMRP (nmol/l, median (25%–75%)
All subjects N = 6980.08 (0.00–0.45)0.40 (0.00–1.11)0.41 (0.00–1.61)31.6170.001 <0.40 (0.00–1.15)73900< 0.001
No disease N = 670.16 (0.00–0.44)0.75 (0.19–1.40)1.34 (0.98–2.41)18.6570.001 <0.84 (0.25–2.55)836.5< 0.001
Pleural plaques N = 4020.07 (0.00–0.33)0.32 (0.00–0.88)0.32 (0.00–0.75)18.8390.001 <0.32 (0.00–0.88)24272.5< 0.001
Asbestosis N = 1430.00 (0.00–0.21)0.18 (0.00–0.64)0.00 (0.00–0.37)5.8170.0550.14 (0.00–0.55)29510.067
No disease or pleural plaques or asbestosis N = 6120.07 (0.00–0.33)0.33 (0.00–0.88)0.33 (0.00–0.76)31.125< 0.0010.33 (0.00–0.87)56942.5< 0.001
MM N = 861.79 (0.34–8.47)2.22 (0.52–8.61)2.87 (1.80–12.14)1.7160.4242.62 (0.88–9.07)9860.595

ROC curve analysis according to MSLN rs1057147 genotype

ComparisonAUC (95% CI)pSMRP cutoff(nmol/l)SensitivitySpecificity
MM vs. all other subjects0.802 (0.740–0.864)< 0.0011.50.5930.930
10.6510.864
1.11a0.6510.885
MM vs. all other subjects with MSLN rs1057147 GG genotype0.827 (0.767–0.888)< 0.0011.50.5930.967
10.6510.925
0.87a0.6860.911
MM vs. all other subjects with MSLN rs1057147 GA genotype0.765 (0.697–0.834)< 0.0011.50.5930.882
10.6510.783
1.57a0.5930.896
MM vs. all other subjects with MSLN rs1057147 AA genotype0.780 (0.702–0.858)< 0.0011.50.5930.878
10.6510.780
1.68a0.5700.927
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