Li Jing, Mo Yuzhen, Wei Qingqing, Chen Jian, Xu Guozeng
Department of Oncology, Liuzhou People's Hospital of Guangxi Medical University, Liuzhou, Guangxi, People's Republic of China.
Department of Radiation Oncology, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, Guangdong, People's Republic of China.
J Inflamm Res. 2023 Feb 21;16:723-735. doi: 10.2147/JIR.S400233. eCollection 2023.
Activated mast cells (AMCs) have been fully researched in inflammation and allergic reactions. However, the protumoral role of AMCs and their biomarker CD203c has not yet been investigated in colorectal cancer (CRC).
We retrospectively collected 449 postoperative patients with stage II-III CRC at two different hospitals as the training (n=310) and validation (n=139) cohorts. These findings were further validated in the independent cohort (Integration of GSE39582 and GSE17536, n=489). The AMC density was assessed using CD203c staining or the CIBERSORT method. The main analysis was recurrence-free survival (RFS) and overall survival (OS).
As an independent factor, high AMC infiltration was associated with worse RFS/OS in the training (hazard ratio [HR]=3.437/3.014, all <0.001) and validation (HR=3.537/2.382, all <0.001) cohorts. We developed and validated an AMC-based nomogram for better stratification for postoperative recurrence in these two cohorts. The role of AMC density was further validated in the independent cohort. High AMC infiltration was associated with decreased RFS/OS after adjuvant chemotherapy (all <0.05). Approximately 74.2% of intramural CD203c AMCs expressed a high level of PD-L1. Multiple immunosuppressive pathways were enriched in high AMC infiltration tumors, including upregulation of the TNF-α/NF-κB and angiogenesis pathways and downregulation of the IFN-γ and IFN-α responses. AMC infiltration was reversely associated with CD8 T-cell infiltration (all <0.05).
High AMC infiltration is associated with worse survival outcomes in stages II-III CRC. AMC density may serve as a potential biomarker for survival benefit in patients receiving adjuvant chemotherapy. This AMC-based nomogram could provide better recurrence stratification. Immunosuppression in tumors with high AMC infiltration might contribute to promoting tumor progression.
活化肥大细胞（AMCs）在炎症和过敏反应方面已得到充分研究。然而，AMCs及其生物标志物CD203c在结直肠癌（CRC）中的促肿瘤作用尚未得到研究。
我们回顾性收集了两家不同医院的449例II - III期CRC术后患者，作为训练队列（n = 310）和验证队列（n = 139）。这些发现在独立队列（整合GSE39582和GSE17536，n = 489）中进一步得到验证。使用CD203c染色或CIBERSORT方法评估AMC密度。主要分析指标为无复发生存期（RFS）和总生存期（OS）。
作为一个独立因素，高AMC浸润与训练队列（风险比[HR]=3.437/3.014，均<0.001）和验证队列（HR = 3.537/2.382，均<0.001）中较差的RFS/OS相关。我们开发并验证了一种基于AMC的列线图，用于在这两个队列中更好地对术后复发进行分层。AMC密度的作用在独立队列中进一步得到验证。高AMC浸润与辅助化疗后RFS/OS降低相关（均<0.05）。大约74.2%的壁内CD203c AMCs表达高水平的PD - L1。多种免疫抑制途径在高AMC浸润肿瘤中富集，包括TNF-α/NF-κB和血管生成途径的上调以及IFN-γ和IFN-α反应的下调。AMC浸润与CD8 T细胞浸润呈负相关（均<0.05）。
高AMC浸润与II - III期CRC患者较差的生存结果相关。AMC密度可能作为接受辅助化疗患者生存获益的潜在生物标志物。这种基于AMC的列线图可以提供更好的复发分层。高AMC浸润肿瘤中的免疫抑制可能有助于促进肿瘤进展。
