Wang Xuan, Zhu Yan-Bin, Cui Hai-Peng, Yu Ting-Ting
Department of Hematology, Affiliated Hospital of Beihua University, Liberation Road No. 12, Jilin, 132011, People's Republic of China,
Tumour Biol. 2014 Sep;35(9):9035-43. doi: 10.1007/s13277-014-2054-2. Epub 2014 Jun 8.
We carried out the current meta-analysis aiming to comprehensively assess the potential role of p15 (INK4b) and p16 (INK4a) aberrant promoter methylation in the pathogenesis of multiple myeloma (MM). The MEDLINE (1966 ~ 2013), Cochrane Library (Issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and Chinese Biomedical (CBM) (1982 ~ 2013) databases were searched without language restrictions. Meta-analyses were conducted using Stata software (Version 12.0, Stata Corporation, College Station, TX, USA). Odds ratios (ORs) and their 95 % confidence intervals (95 %CIs) were calculated. Thirteen clinical case-control studies, which enrolled a total of 465 MM patients and 180 healthy subjects, were included in the meta-analysis. The results of our meta-analysis demonstrated that the frequencies of p15 (INK4b) and p16 (INK4a) promoter methylation in cancer samples were significantly higher than in normal samples (p15 (INK4b) : OR = 6.26, 95 %CI = 3.87 ~ 10.12, P < 0.001; p16 (INK4a) : OR = 2.26, 95 %CI = 1.22 ~ 4.20, P < 0.001). Ethnicity-stratified analysis showed that the aberrant methylation of p15 (INK4b) was significantly related with the risk of MM among both Caucasians and Asians (all P < 0.05). Furthermore, our results also illustrated a strong positive correlation between p16 (INK4a) promoter methylation and the pathogenesis of MM among Asians (OR = 5.17, 95 %CI = 3.45 ~ 7.74, P < 0.001), but not among Caucasians (P > 0.05). The current meta-analysis confirms and reinforces existing findings that p15 (INK4b) and p16 (INK4a) promoter methylation may be closely implicated in the pathogenesis of MM.
我们开展了本次荟萃分析，旨在全面评估p15（INK4b）和p16（INK4a）启动子异常甲基化在多发性骨髓瘤（MM）发病机制中的潜在作用。对MEDLINE（1966年至2013年）、Cochrane图书馆（2013年第12期）、EMBASE（1980年至2013年）、CINAHL（1982年至2013年）、科学网（1945年至2013年）以及中国生物医学文献数据库（CBM）（1982年至2013年）进行了检索，无语言限制。使用Stata软件（版本12.0，美国德克萨斯州大学站Stata公司）进行荟萃分析。计算比值比（OR）及其95%置信区间（95%CI）。本次荟萃分析纳入了13项临床病例对照研究，共纳入465例MM患者和180例健康受试者。我们的荟萃分析结果表明，癌症样本中p15（INK4b）和p16（INK4a）启动子甲基化的频率显著高于正常样本（p15（INK4b）：OR = 6.26，95%CI = 3.87至10.12，P < 0.001；p16（INK4a）：OR = 2.26，95%CI = 1.22至4.20，P < 0.001）。按种族分层分析表明，p15（INK4b）的异常甲基化在白种人和亚洲人中均与MM风险显著相关（所有P < 0.05）。此外，我们的结果还表明，p16（INK4a）启动子甲基化与亚洲人MM发病机制之间存在强正相关（OR = 5.17，95%CI = 3.45至7.74，P < 0.001），但在白种人中无相关性（P > 0.05）。本次荟萃分析证实并强化了现有研究结果，即p15（INK4b）和p16（INK4a）启动子甲基化可能与MM发病机制密切相关。
