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中国生物工程杂志

China Biotechnology
China Biotechnology
China Biotechnology  2023, Vol. 43 Issue (12): 119-127    DOI: 10.13523/j.cb.2310054
    
Clinical Value of Cerebrospinal Fluid Total Protein and Cerebrospinal Fluid Cytokine Levels in Central Nervous System Lymphoma
LUO Xin1,PENG Yu1,TANG Xin-yi1,2,ZHANG Ya-kun1,2,CHEN Shuang1,JIANG Ting-ting1,LIU Yao1,YANG Zai-lin1,***()
1 Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
2 School of Medicine, Chongqing University, Chongqing 400030, China
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Abstract  

Objective: To investigate the diagnostic value of total protein and cytokine levels in cerebrospinal fluid (CSF) on central nervous system lymphoma (CNSL) and its impact on prognosis. Methods: A total of 43 patients who underwent cerebrospinal fluid testing at Chongqing University Cancer Hospital between October 2021 and February 2023 were enrolled into our study. Eighteen patients diagnosed with CNSL were in the CNSL group, and 25 patients with clinical high-risk factors for central invasion of lymphoma but without central nervous infiltration of lymphoma were in the control group. The basic clinical information, CSF biochemical indexes and CSF cytokine were collected. Mann-Whitney U test and t test were used to compare the differences of CSF related indexes between the two groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of CSF related indicators for CNSL patients, and the Kaplan-Meier curve was used to analyze the effect of CSF related indexes on the prognosis of patients. Results: The CNSL group had significantly higher levels of CSF total protein and CSF TNF-α, TNF-β, IL-17A, IL-6, and IL-10 than the control group (P< 0.05). The area under the curve (AUC) of CSF total protein combined with cytokines TNF-α, TNF-β, IL-17A, IL-6 and IL-10 in the diagnosis of CNSL was 0.957, with 94.1% sensitivity, and 95.5% specificity, which was significantly higher than the diagnostic value of CSF total protein and CSF cytokines alone (P< 0.05). The 2-year overall survival (OS) rates of the CNSL and the control groups were 29.1% and 56.0%, and the 2-year progression-free survival (PFS) rates were 23.1% and 68.0%, respectively. Patients in the CNSL group had shorter median PFS (P= 0.03), and there was no significant difference in median OS between the two groups (P= 0.11). Patients with high level of CSF total protein level, high expression of CSF TNF-α, IL-6, and IL-10 and low expression of CSF IL-17A and TNF-β had shorter PFS and OS, but the differences were not statistically significant (P> 0.05). Conclusions: The prognosis of CNSL patients is worse than that of patients with high risk of central nervous infiltration of lymphoma. The expression levels of CSF total protein combined with CSF cytokines TNF-α, TNF-β, IL-17A, IL-6 and IL-10 can assist in the diagnosis of CNSL and have a certain impact on the prognosis of patients with CNSL.

Key words： Central nervous system neoplasms      Lymphoma high risk of central nervous infiltration      Cerebrospinal fluid      Cytokines     
Received: 14 October 2023      Published: 16 January 2024
ZTFLH:  Q354  
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Xin LUO
Yu PENG
Xin-yi TANG
Ya-kun ZHANG
Shuang CHEN
Ting-ting JIANG
Yao LIU
Zai-lin YANG
Cite this article:

Xin LUO, Yu PENG, Xin-yi TANG, Ya-kun ZHANG, Shuang CHEN, Ting-ting JIANG, Yao LIU, Zai-lin YANG. Clinical Value of Cerebrospinal Fluid Total Protein and Cerebrospinal Fluid Cytokine Levels in Central Nervous System Lymphoma. China Biotechnology, 2023, 43(12): 119-127.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2310054     OR     https://manu60.magtech.com.cn/biotech/Y2023/V43/I12/119

分组 例数 性别(男) 年龄(>60) IPI评分(3~5) Ki-67(>90%)
CNSL组 18 13(72.2) 7(38.9) 13(72.2) 13(72.2)
对照组 25 19(76.0) 12(48.0) 19(76.0) 13(52.0)
χ2值 0.078 0.352 0.078 1.790
P值 0.779 0.553 0.779 0.181
Table 1 Basic clinical characteristics of CNSL group and control group
指标 CNSL组 对照组 Z P值
总蛋白/(g/L) 0.637(0.408,3.110) 0.323(0.050,0.493) -3.019 0.003
葡萄糖/(mmol/L) 3.885(2.920,4.250) 3.845(3.480,4.010) -0.190 0.849
氯离子/(mmol/L) 125.96(123.40,127.14) 126.83(124.80,128.56) -1.074 0.283
LDH/(U/L) 22.450(17.700,34.500) 21.100(15.800,23.700) -1.505 0.132
Table 2 Comparison of CSF biochemical examination between groups[M(P25,P75)]
细胞因子 CNSL组/(pg/mL) 对照组/(pg/mL) t/Z P值
IL-22 2.740(2.570,3.58) 2.350(2.030,2.780) -1.668 0.165
TNF-α 9.532±4.275 7.518±2.817 -2.115 0.036
TNF-β 0.540(0.100,1.200) 0.00(0.000,0.390) -2.952 0.003
IFN-γ 3.005(2.415,4.948) 2.700(1.800,3.140) -1.922 0.055
IL-17A 2.885(2.270,4.870) 2.310(1.930,3.050) -2.553 0.011
IL-17F 0.520(0.380,0.670) 0.315(0.290,0.480) -1.249 0.212
IL-4 8.570(6.960,9.24) 7.080(5.410,7.930) -1.726 0.084
IL-8 43.065(29.270,73.450) 32.330(20.040,49.690) -1.354 0.176
IL-2 4.650(4.210,8.130) 4.430(2.990,4.870) -1.802 0.072
IL-6 14.600(10.740,28.060) 8.880(6.900,9.790) -3.818 <0.001
IL-10 17.485(12.72,24.97) 10.840(9.090,13.610) -2.478 0.013
IL-5 6.012±2.514 5.100±1.646 -1.438 0.158
IL-1β 9.392±4.327 8.052±2.682 -1.253 0.217
Table 3 Comparison of CSF cytokine between groups [M(P25,P75), x -± s]
指标 AUC 95% CI值 P值 灵敏度/% 特异度/% 截断值
总蛋白/(g/L) 0.794 0.656~0.933 0.002 94.1 59.1 0.358
TNF-α/(pg/mL) 0.706 0.529~0.883 0.029 70.6 72.7 8.375
TNF-β/(pg/mL) 0.759 0.598~0.921 0.006 52.9 95.5 0.945
IL-17A/(pg/mL) 0.750 0.590~0.910 0.008 70.6 72.7 2.68
IL-6/(pg/mL) 0.882 0.775~0.990 <0.001 82.4 86.4 10.58
IL-10/(pg/mL) 0.779 0.623~0.936 0.003 58.8 90.9 15.75
细胞因子联合 0.936 0.853~1.000 <0.001 88.2 90.9 0.341
总蛋白+细胞因子联合 0.957 0.883~1.000 <0.001 94.1 95.5 0.319
Table 4 Diagnostic value of CSF total protein and cytokines in CNSL
Fig.1 ROC of CSF related indexes combined in the diagnosis of CNSL
Fig.2 Kaplan-Meier survival curves of CNSL and control patients
Fig.3 Kaplan-Meier survival curves of high and low CSF total protein and cytokine expression in CNSL patients
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