MTAP、CDKN2A和CDKN2B在弥漫大B细胞淋巴瘤中的表达及其临床意义

Clinical significance of MTAP, CDKN2A and CDKN2B expression in diffuse large B-cell lymphoma

目的研究弥漫大B细胞淋巴瘤（DLBCL）MTAP、CDKN2A和CDKN2B基因的表达及其临床意义。方法以实时定量聚合酶链反应（PCR）方法检测40例DLBCL及19例淋巴结反应性增生组织中MTAP、CDKN2A和CDKN2B基因的表达情况，结合临床特征进行分析，并进行随访。结果DLBCL组MTAP、CDKN2A和CDKN2B基因表达水平较淋巴结反应性增生组降低，差异有统计学意义（P值分别为0．024、0．044和0．047）；三者表达均与AnnArbor临床分期相关（P值分别为0．004、0．001和0．027）；与患者的性别、年龄、淋巴结外病变累及、ECOG体力评分、骨髓累及、血清乳酸脱氢酶水平均无明显相关（均P〉0．05）。其中MTAP与CDKN2A基因表达情况还与B症状（P值分别为0．003和0．028）和国际预后指数（IPI）相关（P值分别为0．001和0．011）。此外，生存分析结果显示，MTAP、CDKN2A和CDKN2B基因表达水平与患者总生存期相关（P值分别为0．022、0．019和0．042）。结论MTAP、CDKN2A和CDKN2B基因在DLBCL中呈低水平表达，与疾病进展和患者预后有关，可作为反映其生物学行为和评估患者临床疗效的分子标志物。

Objective To investigate the clinical significance of MTAP, CDKN2A and CDKN2B gene expression in diffuse large B-cell lymphoma （DLBCL）. Methods MTAP, CDKN2A and CDKN2B gene expression were assessed by Real-time quantitative PCR in 40 cases of DLBCL and 19 cases of reactive hyperplasia. The clinical and follow-up data were also collected. Results Comparing with reactive hyperplasia, MTAP, CDKN2A and CDKN2B gene expression were decreased in DLBCL group （P = 0.024, 0.044 and 0.047, respectively）. Low-expression of all the three genes were associated with advanced Ann Arbor stage （P =0.004, 0.001 and 0.027, respectively）. No obvious difference were observed according to gender, age, the number of the extra-nodal infiltration, ECOG score, bone marrow involvement and serum LDH level （P 〉0.05）. MTAP and CDKN2A gene expression were associated with B symptoms （P =0.003 and 0.028, respectively） and IPI scores （P =0.001 and 0.011, respectively）. With regard to survival rates, MTAP, CDKN2A and CDKN2B gene expression were significantly associated with OS （P =0.022, 0.019 and 0.042, respectively）. Conclusion MTAP, CDKN2A and CDKN2B gene expression in DLBCL were decreased and related to disease progression and prognosis. They could be considered as biomarkers to evaluate biological behavior and clinical outcome of DLBCL patients.