生物标志物panel 预测胰腺导管腺癌切除术后的生存：多机构队列研究。
Biomarker panel predicts survival after resection in pancreatic ductal adenocarcinoma: A multi-institutional cohort study.
机构信息
The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, NSW Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia.
The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Cancer Diagnosis and Pathology, Kolling Institute, University of Sydney, Sydney, NSW, Australia.
出版信息
Eur J Surg Oncol. 2019 Feb;45(2):218-224. doi: 10.1016/j.ejso.2018.10.050. Epub 2018 Oct 11.
BACKGROUND
Up to 60% of patients who undergo curative-intent pancreatic ductal adenocarcinoma (PDAC) resection experience disease recurrence within six months. We recently published a systematic review of prognostic immunohistochemical biomarkers in PDAC and shortlisted a panel of those reported with the highest level of evidence, including p53, p16, Ca-125, S100A4, FOXC1, EGFR, mesothelin, CD24 and UPAR. This study aims to discover and validate the prognostic significance of a combinatorial panel of tumor biomarkers in patients with resected PDAC.
METHODS
Patients who underwent PDAC resection were included from a single institution discovery cohort and a multi-institutional validation cohort. Tumors in the discovery cohort were stained immunohistochemically for all nine shortlisted biomarkers. Biomarkers significantly associated with overall survival (OS) were reevaluated as a combinatorial panel in both discovery and validation cohorts for its prognostic significance.
RESULTS
224 and 191 patients were included in the discovery and validation cohorts, respectively. In both cohorts, S100A4, Ca-125 and mesothelin expression were associated with shorter OS. In both cohorts, the number of these biomarkers expressed was significantly associated with OS (discovery cohort 36.8 vs. 26.4 vs 16.3 vs 12.8 months, P < 0.001; validation cohort 25.2 vs 18.3 vs 13.6 vs 11.9 months, P = 0.008 for expression of zero, one, two and three biomarkers, respectively). On multivariable analysis, expression of at least one of three biomarkers was independently associated with shorter OS.
CONCLUSION
Combinations of S100A4, Ca-125 and mesothelin expression stratify survival after resection of localized PDAC. Co-expression of all three biomarkers is associated with the poorest prognostic outcome.
背景
多达 60%接受根治性胰腺导管腺癌（PDAC）切除术的患者在六个月内复发疾病。我们最近发表了一篇关于 PDAC 预后免疫组织化学生物标志物的系统评价，并从中筛选出一组报告证据水平最高的生物标志物，包括 p53、p16、Ca-125、S100A4、FOXC1、EGFR、间皮素、CD24 和 UPAR。本研究旨在发现并验证在接受 PDAC 切除术的患者中联合使用肿瘤生物标志物的预后意义。
方法
从单个机构发现队列和多机构验证队列中纳入接受 PDAC 切除术的患者。发现队列中的肿瘤进行所有九个入围生物标志物的免疫组织化学染色。在发现和验证队列中，将与总生存期（OS）显著相关的生物标志物重新评估为组合面板，以评估其预后意义。
结果
分别纳入 224 例和 191 例患者纳入发现和验证队列。在两个队列中，S100A4、Ca-125 和间皮素的表达与较短的 OS 相关。在两个队列中，这些生物标志物的表达数量与 OS 显著相关（发现队列 36.8 vs. 26.4 vs 16.3 vs 12.8 个月，P < 0.001；验证队列 25.2 vs 18.3 vs 13.6 vs 11.9 个月，P = 0.008 用于表达零、一、二和三个生物标志物）。多变量分析显示，至少有一种三种生物标志物的表达与较短的 OS 独立相关。
结论
S100A4、Ca-125 和间皮素表达的组合可分层局部 PDAC 切除后的生存。三种生物标志物的共表达与最差的预后结果相关。
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