基于D50指数的恶性梗阻性黄疸介入疗效及预后评估

Based on D50 Index to Evaluate the the Intervention Effect and Prognosis of Malignant Obstructive Jaundice

目的探讨D50指数评估恶性梗阻性黄疸(MOJ)介入疗效及预后的临床应用价值。方法搜集2020年1月至2020年10月在本院接受检查的对照组(健康人)31名、病例组(MOJ患者)27例的临床资料。分别抽取外周血标本,利用高通量测序获得T细胞表面抗原受体(TCR)可变区序列信息,基于该序列信息分析TCR多样性,采用TCR多样性指数即D50指数,来量化评估免疫力情况;根据D50指数的不同,将MOJ患者免疫力分为优(0.15~0.50)、良(0.10~0.15)、中(0.05~0.10)、差(0~0.05)四个等级,对比分析对照组与病例组之间D50指数的差异。评价MOJ患者不同年龄、性别、体重、肿瘤标志物水平等指标之间的差异,并分析不同免疫级别的MOJ患者总生存期(OS)的差异。结果对照组(31名)中,男10名、女21名,年龄28.0~70.0岁,平均(48.0±10.2)岁,中位D50为0.147(0.017~0.229),免疫力等级为优、良、中、差者分别为15例(48.4%)、8例(25.8%)、6例(19.4%)、2例(6.5%)。病例组(27例)中,男11例、女16例,年龄33.0~75.0岁,平均(55.9±10.3)岁,中位D50为0.069(0.005~0.150),免疫力等级为优、良、中、差者分别为1例(3.7%)、5例(18.5%)、10例(37.0%)、11例(40.7%)。对照组与病例组的D50指数差异有统计学意义(P<0.001)。按照白蛋白-胆红素(ALBI)评分、Child-pugh分级、CA12-5水平及术前是否治疗(化疗或靶向治疗)进行亚组分组,组间D50指数有显著性差异(P<0.05)。免疫力等级为中或差的患者,相比于优或良患者,其Vβ和Jβ基因组合的TCR的丰度呈明显的单调性。不同免疫力等级的患者OS之间有统计学意义(P=0.004,χ^(2)=10.91),其中优良组OS最长。结论D50指数对评价MOJ患者介入疗效及预后有重要的临床意义及应用价值。

Objective To investigate the clinical value of D50 index in evaluating the intervention effect and prognosis of malignant obstructive jaundice(MOJ).Methods The clinical data of 58 people,including 31 cases in the control group(healthy people)and and 27 cases in the research group(interventional therapy),from Jan.2020 to Oct.2020,were collected retrospectively.Peripheral blood were extracted respectively,and the sequence information of TCR variable region was obtained by high-throughput sequencing.Based on the sequence information,TCR diversity was analyzed and TCR diversity index,also called Diversity 50 Index(D50),was used to quantitatively evaluate the immunity.According to the different D50 Index,the immunity of patients with MOJ was divided into four grades,including excellent(0.15-0.50),good(0.10-0.15),moderate(0.05-0.10),poor(0-0.05).The difference of D50 index between control group and research group was compared and analyzed respectively.The immune difference between indicators of patients with MOJ,such as age,gender,weight,and level of tumor markers,was evaluated.The difference of overall survival(OS)in different im-mune levels of patients with MOJ were also analyzed.Results Among the 31 cases of control group,10 were male and 21 were female.The ages were(48.0±10.2)years old(28.0-70.0)years old,the median D50 was 0.147(0.017-0.229),and the immunity grades were excellent,good,moderate,and poor,respectively 15 cases(48.4%),8 cases(25.8%),6 cases(19.4%),2 cases(6.5%).Of the 27 MOJ patients,11 were male and 16 were female,aged(55.9±10.3)years old(33.0-75.0)years old,with the median D50 of 0.069(0.005-0.150),and those with excellent,good,moderate,and poor immunity grades were 1 case(3.7%),5 cases(18.5%),10 cases(37.0%),11 cases(40.7%).The difference of D50 between control group and research group was statistically significant(P<0.001).According to ALBI score,Child-pugh classification,CA12-5 levels and the history of preoperative treatment(chemotherapy or targeted therapy),the MOJ patients were sub-grouped,and there was significant difference in D50 between the sub-groups(P<0.05).Compared patients with excellent or good immune,the moderate or poor immune patients’abundance of T cell receptors(TCR)combined with Vβand Jβgene had obviously monotonic.The OS curve of patients with different immunity levels was statistically significant(P=0.004,χ2=10.91),and the excellent-good group had the longest OS.Conclusion D50 Index has important clinical significance and value for assessment of interventional effect and prognosis in MOJ patients.