Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Int J Cancer. 2018 Nov 1;143(9):2271-2280. doi: 10.1002/ijc.31613. Epub 2018 Aug 7.
The role of mast cells (MCs) in colorectal cancer (CRC) progression was controversial. Thus, our study was designed to evaluate the prognostic value of MCs as well as their correlation with immune microenvironment. A retrospective cohort of CRC patients of stages I-IV was enrolled in our study. Consecutive patients (854) were divided into training set (427 patients) and validation set (427 patients) randomly. The findings were further validated in a GEO cohort, GSE39582 (556 patients). The mast cell density (MCD) was measured by immunohistochemical staining of tryptase or by CIBERSORT algorithm. Low MCD predicted prolonged overall survival (OS) in training and validation set. Moreover, MCD was identified as an independent prognostic indicator in both sets. Better stratification for CRC prognosis can be achieved by building a MCD based nomogram. The prognostic role of MCD was further validated in GSE39582. In addition, MCD predicted improved survival in stages II and III CRC patients receiving adjuvant chemotherapy (ACT). Multiple immune pathways were enriched in low MCD group while cytokines/chemokines promoting anti-tumor immunity were highly expressed in such group. Furthermore, MCD was negatively correlated with CD8+ T cells infiltration. In conclusion, MCD was identified as an independent prognostic factor, as well as a potential biomarker for ACT benefit in stages II and III CRC. Better stratification of CRC prognosis could be achieved by building a MCD based nomogram. Moreover, immunoactivation in low MCD tumors may contributed to improved prognosis.
肥大细胞（MCs）在结直肠癌（CRC）进展中的作用存在争议。因此，我们的研究旨在评估 MCs 的预后价值及其与免疫微环境的相关性。我们纳入了一个 I-IV 期 CRC 患者的回顾性队列。连续患者（854 例）被随机分为训练集（427 例）和验证集（427 例）。研究结果在 GEO 队列 GSE39582（556 例）中进一步验证。通过免疫组化染色 tryptase 或 CIBERSORT 算法测量肥大细胞密度（MCD）。低 MCD 预测训练集和验证集的总生存期（OS）延长。此外，MCD 在两组中均被确定为独立的预后指标。基于 MCD 的列线图可以更好地分层 CRC 预后。MCD 的预后作用在 GSE39582 中得到进一步验证。此外，MCD 预测接受辅助化疗（ACT）的 II 期和 III 期 CRC 患者的生存改善。低 MCD 组中富集了多种免疫途径，而促进抗肿瘤免疫的细胞因子/趋化因子在该组中高表达。此外，MCD 与 CD8+T 细胞浸润呈负相关。总之，MCD 被确定为独立的预后因素，也是 II 期和 III 期 CRC 中 ACT 获益的潜在生物标志物。通过建立基于 MCD 的列线图可以更好地分层 CRC 预后。此外，低 MCD 肿瘤中的免疫激活可能有助于改善预后。
