Low tumor infiltrating mast cell density confers prognostic benefit and reflects immunoactivation in colorectal cancer
Low tumor infiltrating mast cell density confers prognostic benefit and reflects immunoactivation in colorectal cancer
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低肿瘤浸润肥大细胞密度带来预后益处并反映结直肠癌的免疫激活
DOI：
10.1002/ijc.31613
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发表时间：
2018-11-01
影响因子：
6.4
通讯作者：
Xu, Jianmin
中科院分区：
文献类型：
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作者：
Mao, Yihao;Feng, Qingyang;Xu, Jianmin
肥大细胞（MCs）在结直肠癌（CRC）进展中的作用一直存在争议。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。我们的研究纳入了1 - 4期CRC患者的回顾性队列。连续854例患者随机分为训练组（427例）和验证组（427例）。研究结果在GEO队列GSE39582（556例患者）中得到进一步验证。采用胰蛋白酶免疫组化染色或CIBERSORT算法测定肥大细胞密度（MCD）。在训练组和验证组中，低MCD预测延长的总生存期（OS）。此外，在两组患者中，MCD被确定为独立的预后指标。通过建立基于MCD的nomographic，可以更好地对CRC的预后进行分层。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期结直肠癌患者的生存率提高。低MCD组多种免疫通路丰富，促进抗肿瘤免疫的细胞因子/趋化因子在低MCD组高表达。MCD与CD8+ T细胞浸润呈负相关。总之，MCD被认为是一个独立的预后因素，也是ACT在II期和III期CRC中获益的潜在生物标志物。通过建立基于MCD的nomographic，可以更好地对CRC的预后进行分层。此外，低MCD肿瘤的免疫激活可能有助于改善预后。
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.