Shi Yuan, He Wei, Zhong Ming, Yu Minhao
Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Genomics. 2021 Jul;113(4):1988-1998. doi: 10.1016/j.ygeno.2021.04.011. Epub 2021 Apr 16.
Infliximab/adalimumab (IFX/ADA) and vedolizumab (VDZ) are the most widely used biologics in inflammatory bowel diseases. Current models used to predict their efficacies are restricted to either Crohn's disease or ulcerative colitis or to only one type of biologic, which makes them limited in external validation. We therefore designed a comprehensive comparison among these models to identify the most meaningful predictors for patient responses. Several biomarkers and models were compared for their abilities to predict both IFX/ADA and VDZ responses by receiver operating characteristic curves. Least absolute shrinkage and selection operator regression was adopted to determine a simplified gene signature. Verification was performed in biopsy samples by immunohistochemical staining. The GIMATS module (based on counts of IgG plasma cells, inflammatory monocytes, activated T cells, and stromal cells) had the best overall performance for response prediction in both biologics (IFX/ADA, AUC = 0.720-0.853; VDZ, AUC = 0.661-0.728). Based on this module, patients were equally divided into 3 groups: M type (GIMATS-low, metabolism), with a preference for IFX/ADA; I type (GIMATS-high, immune), with a preference for VDZ; and N type (GIMATS-medium, normal), with no preference for either treatment. Furthermore, to improve clinical utility, a simplified 6-gene model, MIN score, was established to determine the baseline expression of G0S2, S100A9, SELE, CHI3L1, MMP1 and CXCL13 and function as a substitute for GIMATS module. Our study suggested that the classification of metabolic or immune type by MIN score was valuable for IBD diagnosis to assist with selection of IFX/ADA and VDZ.
英夫利昔单抗/阿达木单抗（IFX/ADA）和维多珠单抗（VDZ）是炎症性肠病中使用最广泛的生物制剂。目前用于预测其疗效的模型仅限于克罗恩病或溃疡性结肠炎，或者仅适用于一种生物制剂，这使得它们在外部验证方面存在局限性。因此，我们对这些模型进行了全面比较，以确定对患者反应最有意义的预测指标。通过受试者工作特征曲线比较了几种生物标志物和模型预测IFX/ADA和VDZ反应的能力。采用最小绝对收缩和选择算子回归来确定简化的基因特征。通过免疫组织化学染色在活检样本中进行验证。GIMATS模块（基于IgG浆细胞、炎性单核细胞、活化T细胞和基质细胞的计数）在两种生物制剂的反应预测中总体表现最佳（IFX/ADA，AUC = 0.720 - 0.853；VDZ，AUC = 0.661 - 0.728）。基于该模块，患者被平均分为3组：M型（GIMATS低，代谢型），更倾向于使用IFX/ADA；I型（GIMATS高，免疫型），更倾向于使用VDZ；N型（GIMATS中等，正常型），对两种治疗均无偏好。此外，为提高临床实用性，建立了一个简化的6基因模型MIN评分，以确定G0S2、S100A9、SELE、CHI3L1、MMP1和CXCL13的基线表达，并作为GIMATS模块的替代指标。我们的研究表明，通过MIN评分对代谢型或免疫型进行分类对炎症性肠病的诊断有价值，有助于IFX/ADA和VDZ的选择。
