晚期肝癌免疫微环境CD38表达水平与PD-1抑制剂疗效相关性分析

肝脏 ›› 2023, Vol. 28 ›› Issue (1): 75-78.

晚期肝癌免疫微环境CD38表达水平与PD-1抑制剂疗效相关性分析

孙小虎, 王璐, 白静慧, 于洪

110042 沈阳中国医科大学肿瘤医院、辽宁省肿瘤医院胸部放疗病区(孙小虎,于洪),综合内科(王璐,白静慧)

收稿日期:2022-06-28 出版日期:2023-01-31 发布日期:2023-02-21
通讯作者: 于洪,Email:2328901858@qq.com
基金资助:
辽宁省科学技术厅2018年省重点研发计划指导计划项目(201801788)

Correlation analysis of CD38 expression level and efficacy of PD-1 inhibitors in advanced HCC

WANG Lu², SUN Xiao-hu¹, BAI Jing-hui², YU Hong¹

1. Department of Chest Radiation Therapy Ward,Cancer Hospital of China Medical University,Liaoning Cancer Hospital & Institute, Shenyang 110042, China;
2. Comprehensive Internal Medicine,Cancer Hospital of China Medical University,Liaoning Cancer Hospital & Institute, Shenyang 110042, China

Received:2022-06-28 Online:2023-01-31 Published:2023-02-21
Contact: YU Hong,Email:2328901858@qq.com

摘要/Abstract

摘要： 目的探索晚期肝癌(HCC)患者CD38表达水平与PD-1抑制剂疗效的相关性。方法选取2019年1月1日至2020年12月31日辽宁省肿瘤医院接受PD-1抑制剂治疗的晚期肝癌患者60例。采用肝穿刺的方法选取晚期肝癌患者的肿瘤组织,取同期行手术治疗的10份HCC癌旁正常组织作为对照。采用生物信息学分析的方法分析CD38的表达与HCC患者预后的关系;采用免疫组化的方法检测HCC及癌旁正常组织中CD38的表达;对使用PD-1抑制剂治疗的HCC患者进行随访观察,对比CD38的表达水平与患者预后的关系;采用单因素分析的方法筛选出影响晚期HCC患者预后的危险因素。结果 KM-plotter数据库显示在HCC(HR=0.73,95%CI:0.54~0.98,P=0.036)及晚期HCC(HR=0.51,95%CI:0.26~1.00,P=0.045)样本中,CD38表达越高,患者的PFS越长。晚期HCC患者中CD38的表达明显低于癌旁正常组织(χ²=10.126,P=0.006);CD38高表达的患者使用PD-1抑制剂的效果优于CD38低表达的患者(χ²=5.833,P=0.016),CD38的表达与PD-1抑制剂的效果之间具有一定的相关性(r=-0.404, P<0.01)。相对于CD38低表达的患者,CD38高表达的患者具有更长的总生存时间[(24.19±3.89)周比(29.56±3.35)周]和无进展生存时间[(14.32±2.13)周比(17.52±3.02)周](P<0.05)。BCLC分期、Child-Pugh分级及CD38的表达可能与患者的PFS相关。结论晚期HCC患者的CD38表达低,高表达的CD38预示患者PD-1抑制剂效果较好。

关键词: 晚期肝癌, 免疫微环境, CD38, 免疫治疗, PD-1抑制剂

Abstract: Objective To explore the correlation between CD38 expression level and the efficacy of PD-1 inhibitor in patients with advanced hepatic cellular cancer (HCC). Methods 60 patients with advanced liver cancer treated with PD-1 inhibitor from 1 January 2019 to 31 December 2020 were selected as the study subjects and clinical information was collected. The tumor tissues of advanced liver cancer patients were selected by liver puncture, and the adjacent normal tissues of HCC cancer treated surgery our hospital at the same time were selected as the control. The relationship of CD38 expression and the prognosis of HCC patients was analyzed by bioinformatics analysis; Follow-up observations of HCC patients treated with PD-1 inhibitors compared the relationship between CD38 expression levels and patient prognosis; Risk factors were selected to influence the outcome of patients with advanced HCC. Results The KM-plotter database showed that in the HCC(HR=0.73,95%CI:0.54~0.98,P=0.036) and advanced HCC(HR=0.51,95%CI:0.26~1.00,P=0.045) samples, higher CD38 expression and longer PFS; CD38 expression was significantly lower in advanced HCC patients than in adjacent normal tissue(χ²=10.126,P=0.006); Patients with high CD38 expression performed better results with PD-1 inhibitors than those with low CD38 expression (χ²=5.833,P=0.016), and some correlation between CD38 expression and the effect of PD-1 inhibitors (Spearman r=-0.404, P<0.001); Patients with high CD38 expression had longer overall survival (OS, 24.19±3.89 vs 29.56±3.35weeks) and progression-free survival (PFS, 14.32±2.13 vs 17.52±3.02weeks) (P<0.05) than patients with low CD38 expression; BCLC stage, Child-Pugh grade, and CD38 expression may be associated with patient PFS (P<0.05).Conclusion CD38 expression was low in advanced HCC patients, CD38 expression was associated with the therapeutic effect of patient PD-1 inhibitor, and high expression of CD38 predicted a better effect of patient PD-1 inhibitor.

Key words: Advanced hepatic cellular cacner, Immune microenvironment, CD38, Immunotherapy, PD-1 inhibitor

孙小虎, 王璐, 白静慧, 于洪. 晚期肝癌免疫微环境CD38表达水平与PD-1抑制剂疗效相关性分析[J]. 肝脏, 2023, 28(1): 75-78.

WANG Lu, SUN Xiao-hu, BAI Jing-hui, YU Hong. Correlation analysis of CD38 expression level and efficacy of PD-1 inhibitors in advanced HCC[J]. Chinese Hepatolgy, 2023, 28(1): 75-78.

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