编者按： “AME 作者面对面” 是微信公众号 “AME科研时间” 的特色专栏。编辑部精心挑选了发表在 AME 旗下杂志的优秀论著，诚邀作者总结亮点，分享研究成果，旨在进一步推动医学同行之间的交流和进步。
分享团队：
福建医科大学附属协和医院池畔团队
所刊杂志：
Journal of Gastrointestinal Oncology （点击查看杂志详情与影响因子）
文章标题：
一项三阶段跨种族研究显示，B7-H3与结肠癌总生存率相关的重要且是独立的生物标志物（A three-phase trans-ethnic study reveals B7-H3 expression is a significant and independent biomarker associated with colon cancer overall survival）
内容亮点：
B7-H3基因表达与肠癌预后的统计学关联在多个既往研究中结论并不一致。本研究利用TCGA数据库（n=433）、GEO数据库（n=811）以及福建医科大学附属协和医院179例肠癌患者基因表达数据，通过三阶段设计的跨种族（欧洲人、亚洲人）人群关联研究稳健地评估了B7-H3基因表达与肠癌预后间显著的统计学关联性。
作者以TCGA欧洲人群作为筛选集，Cox等比例风险模型结果显示B7-H3基因表达量升高与肠癌患者高死亡风险存在显著统计学关联：HR = 4.6，95% CI: 2.15-9.83，P = 8.37×10−05。在GEO欧洲人群验证集中，两者存在相似的显著关联模式：HR = 1.47，95% CI: 1.12-1.94，P = 0.0056。在协和医院亚洲人群中，该统计学关联依然稳健：HR = 1.63，95% CI: 1.36-1.95，P = 7.91×10−08。
此外，B7-H3基因与其他多个免疫检查点密切相关。但是，校正其他免疫检查点相关基因后，B7-H3基因仍然是肠癌预后的独立预后因子：HR = 1.47，95% CI: 1.07-2.02，P = 0.0184。作者进一步利用B7-H3及其他多个免疫检查点基因构建了肠癌预后预测模型（AUC3-year =0.74 、AUC3-year =0.72），以识别高危死亡人群。
Abstract
Background: There have been inconsistent results and conflicting conclusions among the existing prognostic studies of B7-H3 expression in colon cancer patients. Therefore, the association between B7-H3 expression and colon cancer survival has remained largely unclear.
Methods: We performed a three-phase and trans-ethnic prognostic study of B7-H3 expression in colon cancer patients involving perhaps the largest population to date. In the discovery phase, we utilized a Cox proportional hazards model adjusted for covariates to test the association between B7-H3 expression and colon cancer overall survival (OS) time in a European population from The Cancer Genome Atlas (TCGA) cohort (n=433). In the validation phase I, the association was replicated in a European population from Gene Expression Omnibus (GEO) cohort (n=811). In the validation phase II, we again confirmed the significant association in an Asian population from Fujian Medical University Union Hospital (UNION) cohort (n=179). Furthermore, a series of Kaplan-Meier analysis, bioinformatics analysis of tumor immune microenvironment (TIME), and immune checkpoint prognostic prediction analysis, as well as sensitivity analysis, were also conducted.
Results: Highly expressed B7-H3 was a significant and robust biomarker to colon cancer survival, with a large hazard ratio (HR) [HRTCGA =4.60, 95% confidence interval (CI): 2.15 to 9.83, P=8.37×10−05; HRGEO =1.47, 95% CI: 1.12 to 1.94, P=0.0056; HRUNION =1.63, 95% CI: 1.36 to 1.95, P=7.91×10−08]. We detected an involvement of B7-H3 in the tumor immune microenvironment (TIME). Meanwhile, B7-H3 was significantly and weakly correlated with 6 out of 27 well-recognized immune checkpoint genes. Even after adjusting for effects of other immune checkpoint genes, B7-H3 still exhibited a harmful effect on colon cancer survival using samples from TCGA and GEO cohorts (HR =1.47, 95% CI: 1.07 to 2.02, P=0.0184), indicating that it was an independent prognostic factor of colon cancer. We also proposed an immune checkpoint prognostic risk score which possessed the capability to identify colon cancers with high risk of mortality.
Conclusions: The expression of B7-H3 is a significant, robust, and independent prognostic factor to colon cancer OS.
