Huang Cheng, Zhang Ping, Zhang Depu, Weng Xisheng
Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Oncology, Dezhou People's Hospital, Dezhou, China.
Eur J Clin Invest. 2016 May;46(5):398-407. doi: 10.1111/eci.12608. Epub 2016 Mar 22.
E-cadherin is an invasion suppressor molecule which counteracts tumour metastasis and progression. Slug, one of the crucial transcriptional repressors of E-cadherin gene, has been widely reported on its prognostic role in patients with carcinoma, but the results are controversial. Thus, it is necessary to conduct a meta-analysis to draw a convincing conclusion.
PubMed, Embase and Web of Science databases were searched for studies published until August 1st, 2015. Studies using immunohistochemistry (IHC) to detect the protein expression level in tumour tissues were set as protein group, while studies applying real-time quantitative polymerase chain reaction (RT-qPCR) to probe mRNA transcriptional level were set as mRNA group. Pooled hazard ratio (HR) and their corresponding 95% confidence interval (95% CI) were extracted to evaluate the prognostic role. Funnel plots, Begg's test and Egger's test were used to evaluate the publication bias. Sensitivity and heterogeneity analysis were also conducted.
The pooled HR of 23 studies in the protein group was 1·85 (95% CI: 1·51-2·28, I(2) = 55·4%, P = 0·001), including 1·98 ((95% CI: 1·53-2·58, I(2) = 55·9%, P = 0·004) for overall survival (OS) and 1·46 (95% CI: 1·18-1·82, I(2) = 52·0%, P = 0·012) for progression-free/ recurrence-free/ disease-free/ cancer-free survival (PFS/RFS/DFS/CFS). The high expression of Slug in the protein group indicated poor prognosis of the tumour patients. However, the pooled HR of 6 studies in the mRNA group was 0·85 (95% CI: 0·48-1·53, I(2) = 77·2%, P = 0·001), suggesting no statistical significance. Subgroup analysis was performed to avoid heterogeneity caused by tumour types. Besides, publication bias was not observed in all studies except for the mRNA transcription studies.
The protein expression rather than mRNA transcription of Slug should be considered as a potent biomarker for poor prognosis of tumours, particularly head and neck cancer as well as lung and urinary carcinomas.
E-钙黏蛋白是一种抑制侵袭的分子，可对抗肿瘤转移和进展。Slug是E-钙黏蛋白基因的关键转录抑制因子之一，其在癌症患者中的预后作用已有广泛报道，但结果存在争议。因此，有必要进行一项荟萃分析以得出令人信服的结论。
检索PubMed、Embase和Web of Science数据库，查找截至2015年8月1日发表的研究。将使用免疫组织化学（IHC）检测肿瘤组织中蛋白表达水平的研究设为蛋白组，将应用实时定量聚合酶链反应（RT-qPCR）检测mRNA转录水平的研究设为mRNA组。提取合并风险比（HR）及其相应的95%置信区间（95%CI）以评估预后作用。采用漏斗图、Begg检验和Egger检验评估发表偏倚。还进行了敏感性和异质性分析。
蛋白组23项研究的合并HR为1.85（95%CI：1.51 - 2.28，I² = 55.4%，P = 0.001），其中总生存期（OS）的合并HR为1.98（95%CI：1.53 - 2.58，I² = 55.9%，P = 0.004），无进展/无复发/无疾病/无癌生存期（PFS/RFS/DFS/CFS）的合并HR为1.46（95%CI：1.18 - 1.82，I² = 52.0%，P = 0.012）。蛋白组中Slug的高表达表明肿瘤患者预后不良。然而，mRNA组6项研究的合并HR为0.85（95%CI：0.48 - 1.53，I² = 77.2%，P = 0.001），提示无统计学意义。进行亚组分析以避免肿瘤类型导致的异质性。此外，除mRNA转录研究外，所有研究均未观察到发表偏倚。
应将Slug的蛋白表达而非mRNA转录视为肿瘤预后不良的有效生物标志物，尤其是头颈部癌以及肺癌和泌尿系统癌。
