Ding Kai, Chen Xiaoshuang, Wang Yihao, Liu Hui, Song Wenjing, Li Lijuan, Wang Guojin, Song Jia, Shao Zonghong, Fu Rong
Department of Hematology, Tianjin Medical University General Hospital, 154 Anshan Street, Heping District, Tianjin, 300052, People's Republic of China.
Department of Pathology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
Int J Clin Oncol. 2017 Jun;22(3):585-592. doi: 10.1007/s10147-017-1100-7. Epub 2017 Feb 16.
Early diagnosis and treatment of non-Hodgkin lymphoma (NHL) are progressively important. It has been shown that aberrant promoter methylation contributes to the development and progression of lymphoma. We tried to explore the effect of methylation of p16 and shp1 genes in plasma in the diagnosis of B-NHL patients.
The methylation of p16 and shp1 genes in plasma were detected by methylation specific polymerase chain reaction in 103 patients with B-NHL, and compared with peripheral blood leukocytes (PBLs) and formaldehyde-fixed paraffin-embedded (FFPE) tumor tissues.
The results showed that methylation frequency of p16 in plasma, PBLs, and FFPE tumor tissues of newly diagnosed B-NHL patients were 37% (27/73), 16% (12/73) and 39% (16/41), whereas those of shp1 were 47% (34/73), 25% (18/73) and 63% (26/41). High methylation consistency of p16/shp1 between plasma and FFPE tumor tissues were revealed (the values of kappa: 0.84, 0.80). Moreover, there were a higher frequency of methylated p16 in all three samples in patients with B symptoms and lower platelet count (<100 × 10/L), as well as in patients with stage III/IV in plasma and FFPE tumor tissues. Meanwhile, higher frequency of methylated shp1 was observed in patients with higher LDH level in all three samples.
Methylation of p16/shp1 in plasma can represent their methylation status in tumor tissues, and may be promising biomarkers in early diagnosis and prognosis evaluation in B-NHL.
非霍奇金淋巴瘤（NHL）的早期诊断和治疗日益重要。已有研究表明，异常的启动子甲基化有助于淋巴瘤的发生和发展。我们试图探讨血浆中p16和shp1基因甲基化在B-NHL患者诊断中的作用。
采用甲基化特异性聚合酶链反应检测103例B-NHL患者血浆中p16和shp1基因的甲基化情况，并与外周血白细胞（PBLs）和甲醛固定石蜡包埋（FFPE）肿瘤组织进行比较。
结果显示，新诊断的B-NHL患者血浆、PBLs和FFPE肿瘤组织中p16的甲基化频率分别为37%（27/73）、16%（12/73）和39%（16/41），而shp1的甲基化频率分别为47%（34/73）、25%（18/73）和63%（26/41）。血浆与FFPE肿瘤组织中p16/shp1的甲基化一致性较高（kappa值：0.84，0.80）。此外，有B症状且血小板计数较低（<100×10⁹/L）的患者以及血浆和FFPE肿瘤组织中处于III/IV期的患者，这三个样本中p16甲基化的频率均较高。同时，在所有三个样本中，乳酸脱氢酶（LDH）水平较高的患者中观察到shp1甲基化的频率较高。
血浆中p16/shp1的甲基化可代表其在肿瘤组织中的甲基化状态，可能是B-NHL早期诊断和预后评估中有前景的生物标志物。
