[Expressions and prognostic significance of PTEN and PD-1 protein in patients with classical Hodgkin's lymphoma]

Zhonghua Xue Ye Xue Za Zhi. 2018 Oct 14;39(10):839-844. doi: 10.3760/cma.j.issn.0253-2727.2018.10.010.
[Article in Chinese]

Abstract

Objective: To elucidate the expression levels of key immune biomarkers, phosphate and tension homology deleted on chromosome ten (PTEN) and programmed cell death protein1(PD-1),of different immune tolerance pathway in classic Hodgkin's lymphoma (CHL) to further determine their clinical role and prognostic significance. Methods: The clinical features and prognostic factors of 56 CHL patients, who were admitted to the TianJin Medical University Cancer Institute from February 2003 to August 2013, were retrospectively analyzed. PTEN and PD-1 protein expression levels were analyzed by immunohistochemistry, Epstein-Barr virus encoded RNA (EBER) was performed by in situ hybridization assay. Correlations between the expression of biomarkers and clinicopathologic parameters were examined and survival analyses were performed. Results: This cohort of 56 CHL patients included 34 males and 22 females with a median age of 25 years (ranged from 7 to 71 years). In a univariate analysis, age≥45, IPS score >2, EBER positive, high expression of PTEN protein conferred inferior 5-year OS and 5-year PFS; In a multivariate model, age≥45, IPS score >2, EBER positive, high expression of PTEN protein were identified as the independent adverse prognostic factors for CHL. Conclusions: This study suggested for the first time that PTEN was independent prognostic immune biomarkers in CHL, which provided the novel therapeutic strategy of immune therapy for CHL.

目的: 分析肿瘤免疫耐受信号通路的重要因子PD-1和PTEN在经典型霍奇金淋巴瘤(CHL)患者中的表达及其与患者临床特征和预后的相关性。 方法: 回顾性分析2003年2月至2013年8月诊治的56例CHL患者的临床资料。采用免疫组织化学染色法检测CHL患者PD-1和PTEN蛋白的表达,采用原位杂交法检测EBV及EBV编码的小mRNA(EBER),并结合患者的临床特征与生存状态进行相关性分析。 结果: ①56例患者中,男34例,女22例,中位年龄25(7~71)岁,PTEN阳性者11例(19.64%),PD-1阳性者14例(25.00%)。②PTEN和PD-1表达呈正相关(rs=0.320,P=0.016);PTEN表达与Ann Arbor分期、IPS评分和有无大包块(≥5 cm)明显相关,PD-1仅与有无大包块相关(P值均<0.05)。③中位随访43(5~86)个月,多因素分析结果显示:年龄≥45岁(P<0.001)、IPS评分>2分(P=0.026)、EBER阳性(P=0.004)、PTEN蛋白高表达(P=0.035)是影响患者5年总生存的不良预后因素,也是影响5年无进展生存的不良预后因素(P值分别为0.007、0.014、0.002、0.024)。 结论: 肿瘤免疫逃逸信号通路因子PTEN与CHL患者的预后相关,对CHL患者的预后判断有一定作用,同时也为CHL的免疫治疗提供了新思路和理论依据。.

Keywords: Hodgkin lymphoma; PTEN phosphohydrolase; Prognosis; Programmed cell death 1 receptor.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Female
  • Hodgkin Disease*
  • Humans
  • Male
  • Middle Aged
  • PTEN Phosphohydrolase / analysis*
  • Prognosis
  • Programmed Cell Death 1 Receptor / analysis*
  • Retrospective Studies
  • Young Adult

Substances

  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • PTEN Phosphohydrolase
  • PTEN protein, human