Dai Meng, Yuan Fei, Fu Cuiqun, Shen Guodong, Hu Shilian, Shen Gan
Department of Geriatrics, Anhui Provincial Hospital affiliated to Anhui Medical University, Hefei, Anhui, China.
Anhui Provincial Key Laboratory of Tumour Immunotherapy and Nutrition Therapy, Hefei, Anhui, China.
PLoS One. 2017 Apr 12;12(4):e0175357. doi: 10.1371/journal.pone.0175357. eCollection 2017.
The epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs), but the clinical and prognostic significance of EpCAM in gastric cancer (GC) remains disputable. Motivated by heterogeneous and inconclusive results, we conducted a systematic review and meta-analysis to systematically summarize and elucidate the association between EpCAM overexpression and GC patients.
The PubMed, Cochrane Library, Medline, Web of Knowledge and the China National Knowledge Infrastructure (CNKI) databases were searched to identify relevant studies. The RevMan 5.3 software was used for the meta-analysis. Fixed-effects or random-effects models were applied depending on the presence of heterogeneity. The pooled odds ratio (ORs) and 95% confidence intervals (CIs) were applied to estimate the associations between EpCAM and gastric cancer. For the significant heterogeneity studies, sensitivity analyses were applied based on the population to test the robustness of the pooled results and identify possible sources of heterogeneity.
A total of 11 studies including 1960 GC patients met our inclusion criteria. The results of the meta-analyses revealed that there were significant differences in EpCAM overexpression and tumour size (OR = 2.97, 95% CI: 2.134.13, P < 0.00001), the nature of the tissue (OR = 80.30, 95% CI: 29.21220.81, P < 0.00001), lymph node metastasis (OR = 2.78, 95% CI: 1.236.27, P = 0.01), and the cumulative 5-year overall survival rate (OR = 0.54, 95% CI:0.290.99, P = 0.05). No significant associations were identified between EpCAM overexpression and gender (OR = 0.89, 95% CI: 0.661.19, P = 0.43), age (OR = 1.13, 95% CI: 0.582.20, P = 0.73), tumour stage (OR = 2.26, 95% CI: 0.796.45, P = 0.13), distant metastasis (OR = 2.15, 95% CI: 0.2022.69, P = 0.52), TNM stage (OR = 5.14, 95% CI: 0.7734.37, P = 0.09), Lauren type (OR = 1.18, 95% CI: 0.0816.45, P = 0.9), differentiation (OR = 1.88, 95% CI: 0.65~5.41, P = 0.24). However, due to significant heterogeneity in tumor stage, lymph node metastasis, TNM stage, differentiation and Lauren type, these results should be taken carefully.
The meta-analysis demonstrated that the expression of EpCAM in the gastric cancer group was greater than that in the control group. Moreover, EpCAM overexpression was associated with larger tumour size, lymphnode metastasis and worse prognosis in gastric cancer. Due to significant heterogeneity, the sensitivity analysis suggests that population factor may be an important source of heterogeneity, and these results should be treated with caution. EpCAM may be useful as a novel prognostic factor, and large-scale and well-designed studies are needed to validate our results in the future.
上皮细胞粘附分子(EpCAM)是癌症干细胞(CSCs)最常用的标志物之一,但EpCAM在胃癌(GC)中的临床及预后意义仍存在争议。鉴于结果的异质性和不确定性,我们进行了一项系统评价和荟萃分析,以系统总结并阐明EpCAM过表达与GC患者之间的关联。
检索PubMed、Cochrane图书馆、Medline、Web of Knowledge和中国知网(CNKI)数据库以识别相关研究。使用RevMan 5.3软件进行荟萃分析。根据异质性的存在情况应用固定效应或随机效应模型。合并比值比(OR)和95%置信区间(CI)用于估计EpCAM与胃癌之间的关联。对于存在显著异质性的研究,基于人群进行敏感性分析,以检验合并结果的稳健性并识别可能的异质性来源。
共有11项研究(包括1960例GC患者)符合我们的纳入标准。荟萃分析结果显示,EpCAM过表达与肿瘤大小(OR = 2.97,95%CI:2.134.13,P < 0.00001)、组织性质(OR = 80.30,95%CI:29.21220.81,P < 0.00001)、淋巴结转移(OR = 2.78,95%CI:1.236.27,P = 0.01)以及累积5年总生存率(OR = 0.54,95%CI:0.290.99,P = 0.05)之间存在显著差异。未发现EpCAM过表达与性别(OR = 0.89,95%CI:0.661.19,P = 0.43)、年龄(OR = 1.13,95%CI:0.582.20,P = 0.73)、肿瘤分期(OR = 2.26,95%CI:0.796.45,P = 0.13)、远处转移(OR = 2.15,95%CI:0.2022.69,P = 0.52)、TNM分期(OR = 5.14,95%CI:0.7734.37,P = 0.09)、Lauren分型(OR = 1.18,95%CI:0.0816.45,P = 0.9)、分化程度(OR = 1.88,95%CI:0.65~5.41,P = 0.24)之间存在显著关联。然而,由于肿瘤分期、淋巴结转移、TNM分期、分化程度和Lauren分型存在显著异质性,这些结果应谨慎对待。
荟萃分析表明,胃癌组中EpCAM的表达高于对照组。此外,EpCAM过表达与胃癌中更大的肿瘤大小、淋巴结转移及更差的预后相关。由于存在显著异质性,敏感性分析表明人群因素可能是异质性的重要来源,这些结果应谨慎对待。EpCAM可能作为一种新的预后因素有用,未来需要大规模且设计良好的研究来验证我们的结果。