生物标志物预测巴雷特食管恶性进展风险的荟萃分析。

Meta-analysis of biomarkers predicting risk of malignant progression in Barrett's oesophagus.

机构信息

Department of Surgery, Whiston Hospital, St Helen's and Knowsley Hospitals NHS Foundation Trust, Liverpool, UK.

Department of Hepato-Biliary-Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Br J Surg. 2017 Apr;104(5):493-502. doi: 10.1002/bjs.10484.

DOI:10.1002/bjs.10484

PMID:28295252

Abstract

BACKGROUND

Barrett's oesophagus is a precursor to the development of oesophageal adenocarcinoma. This study sought to clarify the role of genetic, chromosomal and proliferation biomarkers that have been the subjects of multiple studies through meta-analysis.

METHODS

MEDLINE, Embase, PubMed and the Cochrane Library were searched for clinical studies assessing the value of p53, p16, Ki-67 and DNA content abnormalities in Barrett's oesophagus. The main outcome measure was the risk of development of high-grade dysplasia (HGD) or oesophageal adenocarcinoma.

RESULTS

Some 102 studies, with 12 353 samples, were identified. Mutation (diagnostic odds ratio (DOR) 10·91, sensitivity 47 per cent, specificity 92 per cent, positive likelihood ratio (PLR) 4·71, negative likelihood ratio (NLR) 0·65, area under the curve (AUC) 0·792) and loss (DOR 16·16, sensitivity 31 per cent, specificity 98 per cent, PLR 6·66, NLR 0·41, AUC 0·923) of p53 were found to be superior to the other p53 abnormalities (loss of heterozygosity (LOH) and overexpression). Ki-67 had high sensitivity in identifying high-risk patients (DOR 5·54, sensitivity 82 per cent, specificity 48 per cent, PLR 1·59, NLR 0·42, AUC 0·761). Aneuploidy (DOR 12·08, sensitivity 53 per cent, specificity 87 per cent, PLR 4·26, NLR 0·42, AUC 0·846), tetraploidy (DOR 5·87, sensitivity 46 per cent, specificity 85 per cent, PLR 3·47, NLR 0·65, AUC 0·793) and loss of Y chromosome (DOR 9·23, sensitivity 68 per cent, specificity 80 per cent, PLR 2·67, NLR 0·49, AUC 0·807) also predicted malignant development, but p16 aberrations (hypermethylation, LOH, mutation and loss) failed to demonstrate any advantage over the other biomarkers studied.

CONCLUSION

Loss and mutation of p53, and raised level of Ki-67 predicted malignant progression in Barrett's oesophagus.

摘要

背景

巴雷特食管是食管腺癌发展的前兆。本研究旨在通过荟萃分析阐明已在多项研究中作为研究对象的遗传、染色体和增殖生物标志物的作用。

方法

检索 MEDLINE、Embase、PubMed 和 Cochrane 图书馆，以评估巴雷特食管中 p53、p16、Ki-67 和 DNA 含量异常的临床研究。主要观察指标为发展为高级别发育不良（HGD）或食管腺癌的风险。

结果

共确定了 102 项研究，涉及 12353 个样本。p53 突变（诊断优势比（DOR）10.91，灵敏度 47%，特异性 92%，阳性似然比（PLR）4.71，阴性似然比（NLR）0.65，曲线下面积（AUC）0.792）和缺失（DOR 16.16，灵敏度 31%，特异性 98%，PLR 6.66，NLR 0.41，AUC 0.923）优于其他 p53 异常（杂合性丢失（LOH）和过表达）。Ki-67 具有识别高危患者的高灵敏度（DOR 5.54，灵敏度 82%，特异性 48%，PLR 1.59，NLR 0.42，AUC 0.761）。非整倍体（DOR 12.08，灵敏度 53%，特异性 87%，PLR 4.26，NLR 0.42，AUC 0.846）、四倍体（DOR 5.87，灵敏度 46%，特异性 85%，PLR 3.47，NLR 0.65，AUC 0.793）和 Y 染色体缺失（DOR 9.23，灵敏度 68%，特异性 80%，PLR 2.67，NLR 0.49，AUC 0.807）也预测恶性发展，但 p16 异常（甲基化、LOH、突变和缺失）未能显示出比其他研究的生物标志物具有任何优势。