Mehrabi Syrina F, Ghatak Souvik, Mehdawi Lubna M, Topi Geriolda, Satapathy Shakti Ranjan, Sjölander Anita
Cell and Experimental Pathology, Department of Translational Medicine, Lund University, 205 02 Malmö, Sweden.
Cancers (Basel). 2021 Nov 3;13(21):5520. doi: 10.3390/cancers13215520.
The tumor microenvironment has been recognized as a complex network in which immune cells play an important role in cancer progression. We found significantly higher CD66b neutrophil expression in tumor tissue than in matched normal mucosa in the Malmö colon cancer (CC) cohort and poorer survival of stage I-III patients with high CD66b expression. Additionally, mice lacking CysLTR expression () produce less brain-derived neurotrophic factor (BDNF) compared to WT mice and Montelukast (a CysLTR antagonist)-treated mice also reduced BDNF expression in a mouse xenograft model with human SW480 CC cells. CD66b and BDNF expression was significantly higher in patient tumor tissues than in the matched normal mucosa. The univariate Cox PH analysis yielded CD66b and BDNF as an independent predictor of overall survival, which was also found in the public TCGA-COAD dataset. We also discovered a strong positive correlation between CD66b, BDNF and CysLTR expression in the Malmö CC cohort and in the TCGA-COAD dataset. Our data suggest that CD66b/BDNF/CysLTR expression as a prognostic combined biomarker signature for CC patients.
肿瘤微环境已被认为是一个复杂的网络，其中免疫细胞在癌症进展中发挥重要作用。我们发现，在马尔默结肠癌（CC）队列中，肿瘤组织中CD66b中性粒细胞的表达显著高于配对的正常黏膜，且CD66b高表达的I-III期患者生存率较低。此外，与野生型小鼠相比，缺乏半胱氨酰白三烯受体（CysLTR）表达的小鼠产生的脑源性神经营养因子（BDNF）较少，并且在用人SW480 CC细胞建立的小鼠异种移植模型中，孟鲁司特（一种CysLTR拮抗剂）处理的小鼠也降低了BDNF的表达。患者肿瘤组织中CD66b和BDNF的表达显著高于配对的正常黏膜。单因素Cox PH分析得出CD66b和BDNF是总生存期的独立预测因子，这在公开的TCGA-COAD数据集中也得到了证实。我们还在马尔默CC队列和TCGA-COAD数据集中发现CD66b、BDNF和CysLTR表达之间存在强正相关。我们的数据表明，CD66b/BDNF/CysLTR表达可作为CC患者的一种预后联合生物标志物特征。
