Wang Lingxiong, Chang Nijia, Wu Liangliang, Li Jinfeng, Zhang Lijun, Chen Yin, Zhou Zhou, Hao Jianqing, Wang Qiong, Jiao Shunchang
Institute of Oncology, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Department of Oncology, The Second Medical Centre, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Mol Clin Oncol. 2021 Dec;15(6):257. doi: 10.3892/mco.2021.2419. Epub 2021 Oct 14.
An immunoscore for colorectal cancer (CRC) has higher prognostic significance than the TNM staging system. However, the tumor immune microenvironment contains various components that affect clinical prognosis. Therefore, a broader range of immune markers is required to establish an accurate immunoprofile to assess the prognosis of patients with CRC. Using immunohistochemistry combined with multispectral immunohistochemistry and objective assessments, the infiltration of four immune cell types (CD4/CD8/forkhead box p3/CD33 cells), as well as the expression of six co-signaling molecules [programmed cell death 1 (PD1) ligand 1/PD1/T-cell immunoglobulin mucin family member 3/lymphocyte-activating 3/tumor necrosis factor receptor superfamily, member 4/inducible T-cell costimulator] and indoleamine 2,3-dioxygenase 1 were investigated in two independent cohorts of CRC. The patients' overall survival (OS) was evaluated using the Kaplan-Meier method. Using the Cox proportional hazards model, independent prognostic factors of patients were assessed and a nomogram-based immunoprofile system was developed. The predictive ability of the nomogram was determined using a concordance index (C-index) and calibration curve. To facilitate clinical application, a simplified nomogram-based immunoprofile was constructed. Using receiver operating characteristic (ROC) analysis, the predictive accuracy for OS was compared between the immunoprofile and the TNM staging system for patients with stage II/III CRC. According to multivariate analysis for the primary cohort, independent prognostic factors for OS were CD8 tumor-infiltrating lymphocytes, CD33 myeloid-derived suppressor cells and TNM stage, which were included in the nomogram. The C-index of the nomogram for predicting OS was 0.861 (95% CI: 0.796-0.925) for the internal validation and 0.759 (95% CI: 0.714-0.804) for the external validation cohort. The simplified nomogram-based immunoprofile system was able to separate same-stage patients into different risk subgroups, particularly for TNM stage II (P<0.0001) and III (P=0.0002) patients. Pairwise comparison of ROC curves for the immunoprofile and TNM stage systems for patients with stage II/III CRC revealed statistically significant differences (P=0.046) and the Z-statistic value was 1.995. In conclusion, the nomogram-based immunoprofile system provides prognostic accuracy regarding clinical outcomes and is a useful supplement to the TNM staging system for patients with stage II/III CRC.
结直肠癌（CRC）的免疫评分比TNM分期系统具有更高的预后意义。然而，肿瘤免疫微环境包含多种影响临床预后的成分。因此，需要更广泛的免疫标志物来建立准确的免疫图谱，以评估CRC患者的预后。采用免疫组织化学结合多光谱免疫组织化学和客观评估方法，在两个独立的CRC队列中研究了四种免疫细胞类型（CD4/CD8/叉头框p3/CD33细胞）的浸润情况，以及六种共信号分子[程序性细胞死亡蛋白1（PD1）配体1/PD1/T细胞免疫球蛋白粘蛋白家族成员3/淋巴细胞激活分子3/肿瘤坏死因子受体超家族成员4/诱导性T细胞共刺激分子]和吲哚胺2,3-双加氧酶1的表达。采用Kaplan-Meier法评估患者的总生存期（OS）。使用Cox比例风险模型评估患者的独立预后因素，并建立基于列线图的免疫图谱系统。使用一致性指数（C指数）和校准曲线确定列线图的预测能力。为便于临床应用，构建了简化的基于列线图的免疫图谱。采用受试者工作特征（ROC）分析，比较免疫图谱和TNM分期系统对II/III期CRC患者OS的预测准确性。根据对主要队列的多变量分析，OS的独立预后因素为CD8肿瘤浸润淋巴细胞、CD33髓源性抑制细胞和TNM分期，这些因素被纳入列线图。列线图预测OS的C指数在内部验证中为0.861（95%CI：0.796-0.925），在外部验证队列中为0.759（95%CI：0.714-0.804）。简化的基于列线图的免疫图谱系统能够将同阶段患者分为不同的风险亚组，特别是对于TNM II期（P<0.0001）和III期（P=0.0002）患者。II/III期CRC患者免疫图谱和TNM分期系统的ROC曲线两两比较显示出统计学显著差异（P=0.046），Z统计值为1.995。总之，基于列线图的免疫图谱系统提供了关于临床结局的预后准确性，是TNM分期系统对II/III期CRC患者的有用补充。
