Jiang Y, Cao D, Xu C G
Department of Hematology and Research Laboratory of Hematology, West China Hospital of Sichuan University, Chengdu 610041, China.
Zhonghua Xue Ye Xue Za Zhi. 2018 Feb 14;39(2):116-121. doi: 10.3760/cma.j.issn.0253-2727.2018.02.008.
To investigate the expressions of growth arrest-specific protein (GAS1), IL-1 receptor accessory protein (IL-1RAP) and perforin (PRF1) in patients with anaplastic lymphoma kinase positive, anaplastic large cell lymphoma (ALK ALCL) and their relationships with clinical significances and the prognoses of ALK ALCL. Twenty-six formalin-fixed paraffin-embedded (FFPE) samples of ALK ALCL patients who were diagnosed from January 2011 to September 2016 were collected. Twelve FFPE samples of patients with ALKALCL, 13 FFPE samples of patients with peripheral T cell lymphoma (not otherwise specified) (PTCL-NOS) and 8 FFPE samples of patients with angioimmunoblastic T-cell lymphoma (AITL) were used as control groups. RQ-PCR and immunohisto-chemical staining were used to detect the mRNA and protein expressions of GAS1, IL-1RAP and PRF1. The clinical data were analyzed. ①The expression levels of GAS1, IL-1RAP and PRF1 gene and protein in ALK ALCL group were higher than those of the control groups (<0.05), but the expression levels had no statistically significant differences between the control groups (>0.05). ②Patients with elevated lactate dehydrogenase (LDH) (0.77 1.38, =-3.292, =0.001) or International prognostic index (IPI)≥3(0.62 1.29, =-2.495, =0.013) had lower expression level of GAS1. Patients with stage Ⅲ/Ⅳ disease (0.89 1.18, =-2.212, =0.027) or IPI≥3 (0.48 1.13, =-2.008, =0.045) had lower expression level of PRF1. IL-1RAP expression level was not associated with clinical features. ③ALK ALCL patients in complete remission (CR) group had higher expression levels of GAS1 and PRF1 than patients in non-remission (NR) group ( values were 0.016 and 0.009). ④Kaplan-Meier survival analysis showed that patients with high expression levels of GAS1 and PRF1 had longer median overall survival and progression-free survival than patients with low expression levels of GAS1 and PRF1. GAS1, IL-1RAP and PRF1 could be molecular markers for ALK ALCL patients. They have potential diagnostic value and can be used for differential diagnosis in some difficult cases. ALK ALCL patients with high expression levels of GAS1 or PRF1 have better curative effects and prognoses.
探讨生长停滞特异性蛋白（GAS1）、白细胞介素-1受体辅助蛋白（IL-1RAP）和穿孔素（PRF1）在间变性淋巴瘤激酶阳性间变性大细胞淋巴瘤（ALK ALCL）患者中的表达情况及其与临床意义和ALK ALCL预后的关系。收集2011年1月至2016年9月确诊的26例ALK ALCL患者的福尔马林固定石蜡包埋（FFPE）样本。选取12例ALK ALCL患者的FFPE样本、13例外周T细胞淋巴瘤（非特指）（PTCL-NOS）患者的FFPE样本和8例血管免疫母细胞性T细胞淋巴瘤（AITL）患者的FFPE样本作为对照组。采用实时定量聚合酶链反应（RQ-PCR）和免疫组织化学染色检测GAS1、IL-1RAP和PRF1的mRNA和蛋白表达。对临床资料进行分析。①ALK ALCL组GAS1、IL-1RAP和PRF1基因及蛋白表达水平高于对照组（<0.05），但对照组间表达水平差异无统计学意义（>0.05）。②乳酸脱氢酶（LDH）升高（0.77 1.38，=-3.292，=0.001）或国际预后指数（IPI）≥3（0.62 1.29，=-2.495，=0.013）的患者GAS1表达水平较低。Ⅲ/Ⅳ期疾病（0.89 1.18，=-2.212，=0.027）或IPI≥3（0.48 1.13，=-2.008，=0.045）的患者PRF1表达水平较低。IL-1RAP表达水平与临床特征无关。③完全缓解（CR）组ALK ALCL患者GAS1和PRF1表达水平高于未缓解（NR）组（值分别为0.016和0.009）。④Kaplan-Meier生存分析显示，GAS1和PRF1高表达患者的总生存中位数和无进展生存时间长于GAS1和PRF1低表达患者。GAS1、IL-1RAP和PRF1可作为ALK ALCL患者的分子标志物。它们具有潜在的诊断价值，可用于某些疑难病例的鉴别诊断。GAS1或PRF1高表达的ALK ALCL患者疗效和预后较好。
