Pidala Joseph, Sigdel Tara K, Wang Anyou, Hsieh Sue, Inamoto Yoshi, Martin Paul J, Flowers Mary Ed, Hansen John A, Lee Stephanie J, Sarwal Minnie M
Department of Blood and Marrow Transplantation H. Lee Moffitt Cancer Center and Research Institute Tampa FL USA.
Department of Surgery University of California San Francisco San Francisco CA USA.
J Pathol Clin Res. 2016 Nov 29;3(1):3-16. doi: 10.1002/cjp2.58. eCollection 2017 Jan.
Whilst many chronic graft versus host disease (cGVHD) biomarkers have been previously reported, few have been verified in an independent cGVHD cohort. We aimed to verify the diagnostic accuracy of previously reported markers of cGVHD in a multi-centre Chronic GVHD Consortium. A total of 42 RNA and 18 protein candidate biomarkers were assessed amongst 59 cGVHD cases and 33 matched non-GVHD controls. Total RNA was isolated from PBMC, and RNA markers were quantified using PCR. Serum protein markers were quantified using ELISA. A combined 3 RNA biomarker (IRS2, PLEKHF1 and IL1R2) and 2 clinical variables (recipient CMV serostatus and conditioning regimen intensity) panel accurately (AUC 0.81) segregated cGVHD cases from controls. Other studied RNA and protein markers were not confirmed as accurate cGVHD diagnostic biomarkers. The studied markers failed to segregate higher risk cGVHD (per overall NIH 0-3 score, and overlap versus classic cGVHD status). These data support the need for multiple independent verification studies for the ultimate clinical application of cGVHD diagnostic biomarkers.
虽然之前已经报道了许多慢性移植物抗宿主病（cGVHD）生物标志物，但很少有在独立的cGVHD队列中得到验证。我们旨在验证多中心慢性GVHD联盟中先前报道的cGVHD标志物的诊断准确性。在59例cGVHD病例和33例匹配的非GVHD对照中评估了总共42种RNA和18种蛋白质候选生物标志物。从外周血单核细胞中分离总RNA，并使用PCR对RNA标志物进行定量。使用ELISA对血清蛋白标志物进行定量。一个由3种RNA生物标志物（IRS2、PLEKHF1和IL1R2）和2个临床变量（受者巨细胞病毒血清状态和预处理方案强度）组成的组合面板能够准确地（曲线下面积为0.81）将cGVHD病例与对照区分开来。其他研究的RNA和蛋白质标志物未被确认为准确的cGVHD诊断生物标志物。所研究的标志物未能区分高风险的cGVHD（根据美国国立卫生研究院总体0 - 3评分，以及与经典cGVHD状态的重叠情况）。这些数据支持需要进行多项独立验证研究，以实现cGVHD诊断生物标志物的最终临床应用。
