免疫评分在肝癌患者中的预后研究

doi:10.13418/j.issn.1001-165x.2021.01.016

中国临床解剖学杂志 ›› 2021, Vol. 39 ›› Issue (1) : 82-89. DOI: 10.13418/j.issn.1001-165x.2021.01.016

临床研究

免疫评分在肝癌患者中的预后研究

张浩楠^{1, 2}，　张林枝^{2, 3}，　高炜²，　徐彦²，　杨雪玲²，　于海鹏²，　邢文阁²，　司同国²

作者信息 +

The prognostic role of immunoscore in patients with hepatocellular carcinoma

Zhang Haonan^1,2, Zhang Linzhi^2,3, Gao Wei², Xu Yan², Yang Xueling², Yu Haipeng², Xing Wengeng², Si Tongguo²

Author information +

文章历史 +

摘要

目的　探讨免疫评分及PD-L1在肝癌组织的表达情况，分析肝癌患者的免疫评分与其临床病理特征及预后的关系。方法　采用免疫组化检测免疫评分与PD-L1在61例肝癌患者中的表达，分析PD-L1、免疫评分与临床病理特征及预后之间的关系。结果　肝癌中免疫评分较高的表达率为26.2%，较低的表达率为73.8%。统计分析发现免疫评分与AFP增高（P<0.05）及肝内复发（P>0.05）具有相关性；而与患者年龄、性别、肿瘤直径、分化程度、脉管癌栓等临床因素无相关性（P>0.05）。生存分析发现免疫评分较高患者的总生存期与无复发生存期显著高于免疫评分较低的患者（χ2=11.39，P<0.01；χ2=14.78，P<0.01）。肝癌组织PD-L1的阳性表达率为44.3%，对应癌旁低表达，具有统计学差异（χ2=7.313，P<0.01）。PD-L1阳性患者的总生存期与无复发生存期低于PD-L1阴性患者（χ2=5.598，P<0.05；χ2=10.90，P<0.01）。肝癌组织中PD-L1与免疫评分间具有负相关性（χ2=12.703，P<0.01）。结论　免疫评分可作为患者预后的一个标志物，免疫评分高的患者预后较好，反之易早期复发且预后较差；肝癌组织PD-L1与免疫评分之间具有负相关性。

Abstract

Objective　To investigate the expression of immunoscore and PD-L1 in hepatocellular carcinoma(HCC), and to analyze the relationship between the expression of PD-L1 and immunoscore and the clinicopathological characteristics and prognosis of HCC.　Methods　Immunohistochemical staining was used to detect the expression of immunoscore and PD-L1 in 61 cases of hepatocellular carcinoma tissue, and to analyze the relationship between the expression of immunoscore and PD-L1 in hepatocellular carcinoma and different clinicopathological features and prognosis．Results　The expression rate of high-immunoscore was 26.2%, the low-immunoscore expression rate was 73.8%. In clinical indicators，the positive expression rate of immunoscore was negatively related to patient's preoperative AFP level (P<0.005), and intrahepatic recurrence (P<0.05), but not to factors of patient’s age, gender, tumor size, differentiation, and non-vascular invasion correlated (P>0.05). Kaplan–Meier analysis presented that the immunoscore showed good stratification between high-immunoscore and low-immunoscore groups in both overall survival (P<0.01) and progression-free survival (P<0.01), respectively. The positive expression rate of PD-L1 in hepatocellular carcinoma was 44.3%, which was significantly higher than that in normal control group (P<0.01).Kaplan-Meier analysis presented that the PD-L1-positive patients was significantly lower in patients with negative PD-L1-negative patients. In clinical indicators，the positive expression rate of PD-L1 was negatively related to patient’s immunoscore (P<0.01)．Conclusions　The expression of immunoscore can be used as an important prognostic maker for patients with hepatocellular carcinoma. Patients with high-immunoscore are significantly associated with a prolonged OS and PFS, however patients with low-immunoscore are more likely to occur early recurrence, prognosis is even worse. The positive expression rate of PD-L1 is negatively related to patient’s immunoscore.

导出引用

张浩楠, 张林枝, 高炜, 徐彦, 杨雪玲, 于海鹏, 邢文阁, 司同国. 免疫评分在肝癌患者中的预后研究[J]. 中国临床解剖学杂志. 2021, 39(1): 82-89 https://doi.org/10.13418/j.issn.1001-165x.2021.01.016

Zhang Haonan, Zhang Linzhi, Gao Wei, Xu Yan, Yang Xueling, Yu Haipeng, Xing Wengeng, Si Tongguo. The prognostic role of immunoscore in patients with hepatocellular carcinoma[J]. Chinese Journal of Clinical Anatomy. 2021, 39(1): 82-89 https://doi.org/10.13418/j.issn.1001-165x.2021.01.016

中图分类号： R445.3 R734.2

参考文献

[1] Nagtegaal ID, Quirke P, Schmoll HJ. Has the new TNM classification for colorectal cancer improved care[J]. Nat Rev Clin Oncol, 2011, 9(2): 119-123. DOI: 10.1038/nrclinonc.2011.157.
[2] 孙成, 田志刚. 免疫评分: 依据肿瘤组织免疫特性进行预后预测[J]. 中国肿瘤生物治疗杂志, 2015, 22(2): 177-182. DOI: 10.3872/j.issn.1007-385X.2015.2.007.
[3] Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome[J]. Science, 2006, 313(5795): 1960-1964. DOI: 10.1126/science.1129139.
[4] Pagès F, Mlecnik B, Marliot F, et al. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study[J]. Lancet, 2018, 391(10135): 2128-2139. DOI: 10.1126/science.1129139. DOI: 10.1016/S0140-6736(18)30789-X.
[5] Ding W, Xu XZ, Qian Y, et al. Prognostic value of tumor-infiltrating lymphocytes in hepatocellular carcinoma a meta-analysis[J]. Medicine (Baltimore), 2018, 97(50): e13301. DOI: 10.1097/MD. 000000000001 3301.
[6] Yao W, He JC, Yang Y, et al. The prognostic value of tumor-infiltrating lymphocytes in hepatocellular carcinoma: a systematic review and meta-analysis[J]. Sci Rep, 2017, 7(1): 7025. DOI: 10.1038/s41598-017-08128-1.
[7] Cheng CH, Lee CF, Wu TH, et al. Evaluation of the new AJCC staging system for resectable hepatocellular carcinoma. World J Surg Oncol, 2011, 9: 114. DOI: 10.1186/1477-7819-9-114.
[8] 丛文铭, 步宏, 陈杰, et al. 原发性肝癌规范化病理诊断指南(2015年版). 解放军医学杂志, 2015, 40(11): 865-872. DOI:10.11855/j.issn.0577-7402.2015.11.03.
[9] Parpart S, Roessler S, Dong F, et al. Modulation of miR-29 expression by alpha-fetoprotein is linked to the hepatocellular carcinoma epigenome[J]. Hepatology, 2014, 60(3): 872-883. DOI: 10.1002/hep.27200.
[10]Marshall A, Alexander G. Vascular invasion leaves its mark in hepatocellular carcinoma[J]. J Hepatol, 2011, 55(6): 1174-1175. DOI: 10.1016/j.jhep.2011.05.005.
[11] Shah SA, Cleary SP, Wei AC, et al. Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes[J]. Surgery, 2007, 141(3): 330-339. DOI: 10.1016/j.surg.2006.06.028.
[12]Mlecnik B, Bindea G, Angell HK, et al. Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability[J]. Immunity, 2016, 44(3): 698-711. DOI: 10.1016/j.immuni.2016.02.025.
[13]Anitei MG, Zeitoun G, Mlecnik B, et al. Prognostic and predictive values of the immunoscore in patients with rectal cancer[J]. Clin Cancer Res, 2014, 20(7): 1891-1899. DOI: 10.1158/1078-0432.CCR-13-2830.
[14] Galon J, Mlecnik B, Bindea G, et al. Towards the introduction of the 'Immunoscore' in the classification of malignant tumours[J]. J Pathol, 2014, 232(2): 199-209. DOI: 10.1002/path.4287.
[15] Gabrielson A, Wu YN, Wang HK, et al. Intratumoral CD3 and CD8 T-cell densities associated with relapse-free survival in HCC[J]. Cancer Immunol Res, 2016, 4(5): 419-430. DOI: 10.1158/2326-6066.CIR-15-0110.
[16] Sun C, Xu J, Song JX, et al. The predictive value of centre tumour CD8(+) T cells in patients with hepatocellular carcinoma: comparison with immunoscore[J]. Oncotarget, 2015, 6(34): 35602-35615. DOI: 10.18632/oncotarget.5801.
[17]Novikova MV, Khromova NV, Kopnin PB. Components of the hepatocellular carcinoma microenvironment and their role in tumor progression[J]. Biochemistry (Mosc), 2017, 82(8): 861-873. DOI: 10.1134/S0006297917080016.