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GAS1、IL-1RAP、PRF1在ALK阳性间变性大细胞淋巴瘤患者中的表达及其临床意义 被引量:2

Expressions and clinical significance of GAS1, IL-1RAP and PRF1 in patients with ALK positive anaplastic large cell lymphoma
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摘要 【摘要】目的研究生长停滞特异性蛋白(GASl)、IL-1受体辅助蛋白(IL.1RAP)、穿孔素(PRFl)在间变性淋巴瘤激酶阳性的间变性大细胞淋巴瘤(ALK+-ALCL)患者中的表达及其临床意义。方法以2011年1月至2016年9月的26例ALK-ALCL患者为研究对象,以12例ALK—ALCL、13例外周T细胞淋巴瘤非特指型和8例血管免疫母细胞性T细胞淋巴瘤患者为对照。收集所有患者的病理组织标本,采用实时荧光定量PCR和免疫组化法检测标本中GAS1、IL-1RAP、PRF1基因和蛋白表达水平,结合患者的临床资料对数据进行分析。结果①26例ALK+ALCL患者组织中,GASl、IL-1RAP、PRFl基因和蛋白表达水平均高于3个对照组,差异有统计学意义(P值均〈0.05),对照组组间基因与蛋白表达水平差异无统计学意义(P〈0.05)。②存在LDH升高(0.77对1.38,z=-3.292,P=0.001)、国际预后指数(IPI)评分/〉3分(0.62对1.29,Z=-2.495,P=0.013)时,ALK+ALCL患者的GASl基因表达水平降低;疾病分期为Ⅲ/Ⅳ期(0.89对1.18,z=-2.212,P=0.027)、IPI评分≥3分(0.48对1.13,Z=-2.008,P=0.045)时,ALK+ALCL患者的PRFl基因表达水平降低;不同临床特征患者组间IL-1RAP基因表达水平差异均无统计学意义(P值均i〉0.05)。③化疗后达完全缓解的AL+ALCL患者GASl、PRFl基因表达水平差异均无统计学意义(P值分别为0.016、0.009)。④以ALl(LALCL患者中各基因表达的中位数为分界点,GAS1、PRF1基因高表达组患者较低表达组有更长的总生存和无进展生存期(P值均〈0.05)。结论GASl、IL-1RAP、PRFl基因可作为ALK+ALCL的分子标志,有潜在的诊断价值,可用于少数诊断困难病例的鉴别。GAS1、PRF1基因高表达的ALK+ALCL患者疗效及预后更好。 Objective 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 ofALK+ ALCL. Methods 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 ALK+ ALCL, 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. Results (1)The expression levels of GAS1, IL-1RAP and PRF1 gene and protein in ALK+ ALCL group were higher than those of the control groups (P 〈 0.05), but the expression levels had no statistically significant differences between the control groups (P 〉 0.05). (2)Patients with elevated lactate dehydrogenase (LDH) (0.77 vs 1.38,z = - 3.292,P = 0.001) or International prognostic index (IPI)≥3(0.62 vs 1.29, z = - 2.495, P= 0.013) had lower expression level of GAS1. Patients with stage Ⅲ/Ⅳ disease (0.89 vs 1.18,z= - 2.212, P= 0.027) or IPI≥3 (0.48 vs 1.13, z= - 2.008, P= 0.045) had lower expression level of PRF1. IL-1RAP expression level was not associated with clinical features. (3)ALK+ ALCL patients in complete remission (CR) group had higher expression levels of GAS1 and PRF1 than patients in non-remission (NR) group (P values were 0.016 and 0.009). (4)Kaplan-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. Conclusion 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 GAS 1 or PRF 1 have better curative effects and prognoses.
出处 《中华血液学杂志》 CAS CSCD 北大核心 2018年第2期116-121,共6页 Chinese Journal of Hematology
关键词 淋巴瘤 大细胞 间变性 基因 GAS1 基因 IL-1RAP 基因 PRF1 Lymphoma, large-cell, anaplastic Gene, GAS1 Gene, IL-1RAP Gene, PRF1
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