Observational Study
Copyright ©The Author(s) 2021.
World J Clin Oncol. Oct 24, 2021; 12(10): 947-959
Published online Oct 24, 2021. doi: 10.5306/wjco.v12.i10.947
Table 1 Demographic features and concentrations of molecular markers of recruited subjects
No.
Factors
Controls
IDH-mutant
IDH-wildtype
1Sample size, (n)(n = 45)6030
2Sex, M/FM = 30; F = 15M = 51; F = 9M = 25; F = 5
3Age (yr)25 (21-50)35.0 (13-75)51.5 (25-76)
4Site-Frontal = 37/Non-frontal = 23Frontal = 12/Non-frontal = 18
5EOR-STR = 38; GTR = 14STR = 30; GTR = 0
6OS-28.5 (1-158)6.5 (1-38)
Values presented as median with range. M: Male; F: Female; EOR: Extent of resection; STR: Sub-total resection; GTR: Gross total resection; OS: Overall survival; IDH: Isocitrate dehydrogenase.
Table 2 Concentrations of molecular markers of recruited subjects of glioma patients in terms of isocitrate dehydrogenase mutant and wildtype glioma
No.
Factors
Controls (n = 45)
IDH-mutant (n = 60)
IDH-wildtype (n = 30)
P value
1KYN (ng/mL)5.009 (0.052-34.43)77.155 (1.56-387.44)237.318 (53.43-894.95)< 0.0001c
2IL-6 (pg/mL)37.009 (6.715-62.49)68.62 (21.85-209.73)197.672 (59.217-803.711)< 0.0001c
3NLR1.59 (0.87-2.8)3.67 (1.23-11.5)5.585 (3.1-18)0.0002c
4TIMP-1 (ng/mL)38.03 (10.26-73.99)82.54 (25.09-131.30)107.01 (37.175-185.09)0.0405a
5hTERT (ng/mL)1.029 (0.075-1.58)1.364 (0.1-6.886)2.185 (0.565-8.84)< 0.0001c
aP < 0.05.
cP < 0.001.
Median with ranges of all circulatory markers in controls, isocitrate dehydrogenase (IDH)-m and IDH-w. KYN: Kynurenine; IL-6: Interleukin-6; NLR: Neutrophil-lymphocytes ratio; TIMP-1: Tissue inhibitor metalloproteases-1; hTERT: Human telomerase reverse transcriptase; IDH: Isocitrate dehydrogenase.
Table 3 Spearman coefficient correlation of circulatory markers with overall survival, histological grade and Kynurenine
No.
Circulatory markers
Spearman r
95%CI
P value
Correlation with OS
1KYN (ng/mL)-0.6154-0.7324 to -0.463< 0.0001c
2IL-6 (pg/mL)-0.5531-0.6854 to -0.3855< 0.0001c
3NLR-0.5696-0.698 to -0.4058< 0.0001c
4TIMP-1 (ng/mL)-0.4831-0.6312 to -0.3011< 0.0001c
5hTERT (ng/mL)-0.4386-0.5960 to -0.2489< 0.0001c
Correlation with grade
6KYN (ng/mL)0.54090.3705 to 0.6761< 0.0001c
7IL-6 (pg/mL)0.64000.4944 to 0.7507< 0.0001c
8NLR0.49820.3190 to 0.6430< 0.0001c
9TIMP-1 (ng/mL)0.26140.05118 to 0.44950.0128a
10hTERT (ng/mL)0.30000.06441 to 0.48340.0102a
Correlation with KYN
11IL-6 (pg/mL)0.49190.3115 to 0.638< 0.0001c
12NLR0.40840.214 to 0.5717< 0.0001c
13TIMP-1 (ng/mL)0.47180.2877 to 0.6223< 0.0001c
14hTERT (ng/mL)0.35040.1485 to 0.52430.0007c
aP < 0.05.
cP < 0.001.
An extremely significant inverse correlation of kynurenine, interleukin-6, neutrophil-lymphocytes ratio, tissue inhibitor metalloproteases-1 and human telomerase reverse transcriptase was obtained with respect to overall survival. A significant positive correlation of interleukin-6, neutrophil-lymphocytes ratio, tissue inhibitor metalloproteases-1 and human telomerase reverse transcriptase was obtained with respect to grades and kynurenine circulatory levels. OS: Overall survival; KYN: Kynurenine; IL-6: Interleukin-6; NLR:Neutrophil lymphocytes ratio; TIMP-1: Tissue inhibitor metalloproteases-1; hTERT: Human telomerase reverse transcriptase; CI: Confidence interval.
Table 4 Univariate and multivariate Cox regression analysis of variables
No.VariableUnivariate
Multivariate
HR (95%CI)
P value
HR (95%CI)
P value
1KYN (ng/mL)1.0037 (1.0026-1.0048)0.0001c1.0024 (1.0011-1.0037)0.0003c
2IL-6 (pg/mL)1.0032 (1.0021-1.0042)0.0001c1.0022 (1.0010-1.0035)0.0004c
3NLR1.2437 (1.1621-1.3312)0.0001c1.2085 (1.1138-1.3114)0.0001c
4TIMP-1 (ng/mL)1.0150 (1.0075-1.0225)0.0001c1.0046 (0.9975-1.0118)0.2042
5hTERT (ng/mL)1.2681 (1.1498-1.3987)0.0001c1.2303 (1.0749-1.4080)0.0026b
5Age(yr)1.0245 (1.0108-1.0383)0.0004c1.0090 (0.9938-1.0233)0.2165
6EOR1.3379 (1.8805-3.0328)0.1726NANA
7Site0.9527 (0.6221-1.4589)0.8236NANA
8Therapy0.8507 (0.2201-1.3578)0.906NANA
bP < 0.01.
cP < 0.001; indicated a significant association.
Results are presented as estimated hazards ratio with 95% confidence interval for specific variables. Variables with a significant P value (< 0.05) in univariate Cox-regression model were selected and analyzed using multivariate Cox-regression. CI: Confidence interval; EOR: Extent of resection; HR: Hazard ratio; hTERT: Human telomerase reverse transcriptase; KYN: Kynurenine; IL-6: Interleukin-6; NA: Not assessed; NLR: Neutrophil-lymphocytes ratio; TIMP-1: Tissue inhibitor metalloproteases-1.
Table 5 Difference in preoperative and postoperative concentrations of markers in blood samples collected in a 3-mo follow-up
No
Markers
Preoperative concentration
3-mo postoperative concentration
P value
rs value
1KYN (ng/mL)126.1 (19.410-387.440)75.405 (16.340-227.400)0.0148a0.4509
2IL-6 (pg/mL)75.65 (23.96-209.73)60.03 (21.85-140.77)0.0107a0.1850
3NLR4.30 (1.43-15.00)2.93 (0.80-6.90)0.0038b0.7260
4hTERT (ng/L)2.27 (1.16-6.86)1.33 (0.78-4.78)0.0016b0.6574
aP < 0.05.
bP < 0.01.
Concentration presented as median with ranges. hTERT: Human telomerase reverse transcriptase; IL-6: Interleukin-6; KYN: Kynurenine; NLR: Neutrophil-lymphocytes ratio.