血清TIM-3对肝癌患者诊断价值的研究

摘要/Abstract

摘要：

目的分析T细胞免疫球蛋白黏蛋白-3（TIM-3）在肝癌患者血清中的水平变化及其诊断价值。方法选取2021年3月至2021年5月于空军军医大学第二附属医院就诊的37例乙型病毒性肝炎患者（乙型肝炎组）、44例肝硬化患者（肝硬化组）和27例肝癌患者（肝癌组）,同期健康体检者35例作为健康对照组。检测血清样本中甲胎蛋白（AFP）、肝功能指标和TIM-3水平,分析组间水平差异。采用Spearman相关分析TIM-3与AFP和肝功能指标之间的相关性。采用受试者工作特征（ROC）曲线分析TIM-3对肝癌的诊断价值。结果AFP在乙型肝炎组、肝硬化组和肝癌组的差异具有统计学意义（χ²=11.75,P=0.003）,总胆红素（χ²=22.85,P<0.001）、直接胆红素（χ²=25.90,P<0.001）、间接胆红素（χ²=19.92,P<0.001）、谷丙转氨酶（χ²=36.64,P<0.001）、谷草转氨酶（χ²=26.26,P<0.001）、谷草转氨酶/谷丙转氨酶（χ²=34.67,P<0.001）、总胆汁酸（χ²=13.10,P<0.001）在乙型肝炎组、肝硬化组和肝癌组间差异均具有统计学意义。健康对照组、乙型肝炎组、肝硬化组和肝癌组患者血清TIM-3水平分别为11.1（4.2,14.4） ng/ml、12.7（4.3,23.9）ng/ml、11.4（3.4,17.0）ng/ml、15.7（10.5,21.2）ng/ml,差异有统计学意义（χ²=11.85,P=0.008）;肝癌组与健康对照组、肝硬化组差异均有统计学意义（均P<0.05）。Spearman相关性分析显示,4组患者血清TIM-3与AFP均无关（r=0.05,P=0.791;r=0.18,P=0.497;r=0.03,P=0.883;r=0.24,P=0.396）;健康对照组血清TIM-3与总蛋白（r=0.36,P=0.036）、乙型肝炎组血清TIM-3与球蛋白（r=0.35,P=0.034）、肝癌组血清TIM-3与总胆汁酸（r=0.46,P=0.017）均有关。ROC曲线结果显示,以健康人群作为对照,血清TIM-3对肝癌的诊断敏感性为48.10%,特异性为91.43%;以健康人群和肝硬化患者合并作为对照,血清TIM-3对肝癌的诊断敏感性为96.30%,特异性为41.77%;以健康人群、乙型肝炎和肝硬化患者合并作为对照,血清TIM-3对肝癌的诊断敏感性为96.30%,特异性为40.52%。结论肝癌患者血清中TIM-3水平显著升高,对肝癌具有一定的诊断价值,可作为肝癌患者诊断标志物和潜在治疗靶点。

关键词:肝肿瘤,肝硬化,TIM-3

Abstract:

ObjectiveTo analyze the changes of T cell immunoglobulin- and mucin-domain-containing molecule-3 （TIM-3） in serum of patients with liver cancer and its diagnostic value.MethodsFrom March 2021 to May 2021, 37 patients with viral hepatitis type B （hepatitis B group）, 44 patients with liver cirrhosis （liver cirrhosis group） and 27 patients with liver cancer （liver cancer group） were selected in the Second Affiliated Hospital of Air Force Medical University, and 35 healthy subjects who underwent physical examination during the same period were selected as the healthy control group. The serum alpha fetoprotein （AFP）, liver function indexes and TIM-3 levels were detected, and the differences among groups were analyzed. The correlations between TIM-3 and AFP and liver function indexes were analyzed by Spearman correlation. Receiver operating characteristic （ROC） curve was used to analyze the diagnostic value of TIM-3 in liver cancer.ResultsThere was a statistically significant difference in AFP among the hepatitis B group, liver cirrhosis group and liver cancer group （χ²=11.75,P=0.003）. There were statistically significant differences in total bilirubin （χ²=22.85,P<0.001）, direct bilirubin （χ²=25.90,P<0.001）, indirect bilirubin （χ²=19.92,P<0.001）, alanine aminotransferase （χ²=36.64,P<0.001）, aspertate aminotransferase （χ²=26.26,P<0.001）, aspertate aminotransferase/alanine aminotransferase （χ²=34.67,P<0.001） and total bile acid （χ²=13.10,P<0.001） among the hepatitis B group, liver cirrhosis group and liver cancer group. The serum levels of TIM-3 in the healthy control group, hepatitis B group, liver cirrhosis group and liver cancer group were 11.1 （4.2, 14.4） ng/ml, 12.7 （4.3, 23.9） ng/ml, 11.4 （3.4, 17.0） ng/ml and 15.7 （10.5, 21.2） ng/ml, with a statistically significant difference （χ²=11.85,P=0.008）. There were statistically significant differences between the liver cancer group and healthy control group and liver cirrhosis group （bothP<0.05）. Spearman correlation analysis showed that TIM-3 had no correlation with AFP in the four groups （r=0.05,P=0.791;r=0.18,P=0.497;r=0.03,P=0.883;r=0.24,P=0.396）. There were correlations between serum TIM-3 and total protein in the healthy control group （r=0.36,P=0.036）, serum TIM-3 and globulin in the hepatitis B group （r=0.35,P=0.034）, and serum TIM-3 and total bile acid in the liver cancer group （r=0.46,P=0.017）. ROC curve analysis showed that the sensitivity of serum TIM-3 for the diagnosis of liver cancer was 48.10%, and the specificity was 91.43%, when taking healthy subjects as the control group. The sensitivity of serum TIM-3 for the diagnosis of liver cancer was 96.30%, and the specificity was 41.77%, when taking healthy subjects and liver cirrhosis patients as the control group. The sensitivity of serum TIM-3 for the diagnosis of liver cancer was 96.30%, and the specificity was 40.52%, when taking healthy subjects, hepatitis B patients and liver cirrhosis patients as the control group.ConclusionThe serum level of TIM-3 in patients with liver cancer is significantly increased, which has certain diagnostic value for liver cancer, and can be used as a diagnostic marker and potential therapeutic target for liver cancer patients.

Key words:Liver neoplasms,Liver cirrhosis,TIM-3

和婷, 王希, 张惠中, 刘昕阳, 王会平, 董轲. 血清TIM-3对肝癌患者诊断价值的研究[J]. 国际肿瘤学杂志, 2022, 49(9): 537-542.

He Ting, Wang Xi, Zhang Huizhong, Liu Xinyang, Wang Huiping, Dong Ke. Diagnostic value of serum TIM-3 in patients with liver cancer[J]. Journal of International Oncology, 2022, 49(9): 537-542.

图/表4

项目	健康对照组（n=35）	乙型肝炎组（n=37）	肝硬化组（n=44）	肝癌组（n=27）	χ²/F值	P值
性别
男	16（45.7）	22（59.5）	31（70.5）	16（59.3）	2.00	0.157
女	19（54.3）	15（40.5）	13（29.5）	11（40.7）
年龄（岁）	47.7±10.8	44.8±11.7	49.9±11.8	52.6±9.4	2.90	0.153

表1

表2

3组患者AFP和肝功能指标水平比较[M(Q1,Q3）]"

指标	乙型肝炎组（n=37）	肝硬化组（n=44）	肝癌组（n=27）	χ²值	P值
AFP（ng/ml）	15.2（8.6,317.5）	3.4（2.0,127.6）^a	47.3（16.7,232.0）	11.75	0.003
总蛋白（g/L）	62.6（55.2,68.7）	65.8（56.7,71.9）	62.3（59.4,68.0）	0.44	0.804
白蛋白（g/L）	33.9（30.6,40.4）	33.6（29.4,43.5）	32.6（31.1,36.8）	0.37	0.833
球蛋白（g/L）	27.2（23.5,32.0）	26.5（22.2,32.6）	28.7（24.0,35.4）	1.14	0.566
白蛋白/球蛋白	1.3（1.0,1.6）	1.3（0.9,1.7）	1.2（1.0,1.6）	0.69	0.709
总胆红素（μmol/L）	75.4（23.3,209.0）	21.9（14.9,36.8）^ab	30.1（23.6,55.8）^b	22.85	<0.001
直接胆红素（μmol/L）	44.4（9.7,110.8）	8.0（5.3,16.8）^ab	12.3（10.0,26.8）^b	25.90	<0.001
间接胆红素（μmol/L）	32.5（13.7,93.2）	13.9（9.4,21.2）^b	15.8（13.1,29.0）^b	19.92	<0.001
谷丙转氨酶（U/L）	142.0（62.0,370.0）	26.0（18.0,41.5）^b	31.0（22.0,51.0）^b	36.64	<0.001
谷草转氨酶（U/L）	109.0（44.5,219.0）	33.0（26.0,50.0）^b	55.0（37.0,161.0）^b	26.26	<0.001
谷草转氨酶/谷丙转氨酶	0.7（0.6,1.1）	1.3（1.0,1.6）^ab	1.6（1.2,3.0）^b	34.67	<0.001
总胆汁酸（μmol/L）	103.9（14.1,353.1）	14.3（3.2,64.1）^ab	15.9（8.3,87.7）^b	13.10	<0.001

表2

表3

4组患者血清TIM-3水平与AFP、肝功能指标的相关系数"

指标	健康对照组（n=35）		乙型肝炎组（n=37）		肝硬化组（n=44）		肝癌组（n=27）
指标	r值	P值	r值	P值	r值	P值	r值	P值
AFP	0.05	0.791	0.18	0.497	0.03	0.883	0.24	0.396
总蛋白	0.36	0.036	0.22	0.186	0.14	0.411	0.08	0.684
白蛋白	0.27	0.122	<0.01	0.995	0.19	0.250	0.01	0.949
球蛋白	0.24	0.166	0.35	0.034	0.17	0.304	0.08	0.709
白蛋白/球蛋白	0.09	0.587	0.28	0.096	0.14	0.421	0.13	0.527
总胆红素	0.01	0.968	0.04	0.812	0.26	0.126	0.01	0.973
直接胆红素	0.01	0.978	0.03	0.852	0.26	0.120	0.06	0.747
间接胆红素	0.01	0.945	0.05	0.771	0.22	0.182	0.05	0.817
谷丙转氨酶	0.15	0.378	0.02	0.726	0.22	0.198	0.23	0.256
谷草转氨酶	0.15	0.395	0.06	0.557	0.22	0.193	0.10	0.622
谷草转氨酶/谷丙转氨酶	0.20	0.255	0.10	0.805	0.08	0.654	0.26	0.193
总胆汁酸	0.11	0.535	0.09	0.497	0.18	0.288	0.46	0.017

表3

图1

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