Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis.
Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis.
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DOI：
10.1371/journal.pone.0142080
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yan C
中科院分区：
文献类型：
--
作者：
Huang YK;Yu JC;Kang WM;Ma ZQ;Ye X;Tian SB;Yan C
人胃蛋白酶原被认为是筛选萎缩性胃炎（AG）和胃癌（GC）的有前途的血清学生物标志物。然而，文献中关于血清胃蛋白酶原（SPG）检测GC和AG的有效性存在争议。因此，我们进行了一项系统性综述和荟萃分析，以评估SPG在GC和AG检测中的诊断准确性。我们检索了PubMed、Embase和中国知网（CNKI）中截至2014年9月30日发表的相关原始研究。基于双变量随机效应模型，使用汇总敏感性、特异性、阳性诊断似然比（DLR+）、阴性诊断似然比（DLR-）、汇总受试者工作特征曲线下面积（AUC）和诊断比值比（DOR）评价SPG在GC和AG筛查中的作用。通过I2统计量评价研究间异质性，并使用Begg和Mazumdar检验评估发表偏倚。进行荟萃回归和亚组分析以探索研究异质性。荟萃分析共纳入了31项研究，涉及1,520例GC患者和2,265例AG患者。使用SPG进行GC筛查的总体敏感性、特异性、DLR+、DLR-、AUC和DOR为0.69（95% CI：0.60-0.76），0.73（95% CI：0.62-0.82）、2.57（95% CI：1.82-3.62）和0.43（95% CI：0.34-0.54）、0.76（95% CI：0.72-0.80）和6.01（95% CI：3.69-9.79）。对于AG筛查，汇总灵敏度、特异性、DLR+、DLR-、AUC和DOR为0.69（95%CI：0.55-0.80），0.88（95% CI：0.77-0.94）、5.80（95% CI：3.06-10.99）和0.35（95% CI：0.24-0.51）、0.85（95% CI：0.82-0.88）和16.50（95% CI：8.18-33.28）。在亚组分析中，联合使用PGI浓度和PGI：PGII比值作为GC筛查SPG的测量值的敏感性为0.70（95% CI：0.66-0.75），特异性为0.79（95% CI：0.79-0.80），DOR为6.92（95% CI：4.36-11.00），AUC为0.78（95% CI：0.72-0.81），而使用PGI浓度的敏感性为0.55（95% CI：0.51-0.60），特异性0.79（95% CI：0.76-0.82），DOR 6.88（95% CI：2.30-20.60），AUC 0.77（95% CI：0.73-0.92）。对于AG筛查，使用PGI：PGII的比值作为SPG的测量值，其灵敏度为0.69（95% CI：0.52-0.83），特异性为0.84（95% CI：0.68-0.93），DOR为11.51（95% CI：6.14-21.56），AUC为0.83（95%CI：0.80-0.86），使用PGI浓度与PGI：PGII比值组合的产率敏感性为0.79（95% CI：0.72-0.85），特异性为0.89（95% CI：0.85-0.93），DOR为24.64（95% CI：6.95-87.37），AUC为0.87（95%CI：0.81-0.92），同时，使用浓度的PGI产量敏感性为0.46（95% CI：0.38-0.54），特异性0.93（95% CI：0.91-0.95），DOR 19.86（95% CI：0.86-456.91），AUC 0.86（95% CI：0.52-1.00）。SPG作为一种非侵入性的、基于人群的筛查工具在GC和AG筛查中具有很大的潜力。此外，考虑到纳入研究的潜在发表偏倚和高度异质性，未来还需要进一步的高质量研究。
Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection. We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I2 statistics and publication bias was assessed using Begg and Mazumdar’s test. Meta-regression and subgroup analyses were performed to explore study heterogeneity. In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60–0.76), 0.73 (95% CI: 0.62–0.82), 2.57 (95% CI: 1.82–3.62), and 0.43 (95% CI: 0.34–0.54), 0.76 (95% CI: 0.72–0.80) and 6.01 (95% CI: 3.69–9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55–0.80), 0.88 (95% CI: 0.77–0.94), 5.80 (95% CI: 3.06–10.99), and 0.35 (95% CI: 0.24–0.51), 0.85 (95% CI: 0.82–0.88) and 16.50 (95% CI: 8.18–33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66–0.75), specificity of 0.79 (95% CI: 0.79–0.80), DOR of 6.92 (95% CI: 4.36–11.00), and AUC of 0.78 (95% CI: 0.72–0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51–0.60), specificity of 0.79 (95% CI: 0.76–0.82), DOR of 6.88 (95% CI: 2.30–20.60), and AUC of 0.77 (95% CI: 0.73–0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52–0.83), specificity of 0.84 (95% CI: 0.68–0.93), DOR of 11.51 (95% CI: 6.14–21.56), and AUC of 0.83 (95% CI: 0.80–0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72–0.85), specificity of 0.89 (95% CI: 0.85–0.93), DOR of 24.64 (95% CI: 6.95–87.37), and AUC of 0.87 (95% CI: 0.81–0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38–0.54), specificity of 0.93 (95% CI: 0.91–0.95), DOR of 19.86 (95% CI: 0.86–456.91), and AUC of 0.86 (95% CI: 0.52–1.00). SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future.