Ko Eun-A, Sanders Kenton M, Zhou Tong
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA.
Oncoimmunology. 2017 Aug 8;6(11):e1360457. doi: 10.1080/2162402X.2017.1360457. eCollection 2017.
To date, the exact impact of mast cells in tumor microenvironment is still controversial because of inconsistency in observations regarding the relationship between mast cell infiltrates and cancer development and prognosis. The discrepancies in previous studies have motivated us to examine the roles of mast cells in cancer pathology from different perspectives. Here, we investigated the impact of mast cells on transcriptomic profiles in the tissue microenvironment. Mice carrying the mutation in ( ) are deficient in mast cell production and were used to assess the influence of mast cells on gene expression. By examining the transcriptomic profile among wild-type mice, mice, and mice with mast cell engraftment, we identified a list of "mast cell-dependent genes," which are enriched for cancer-related pathways. Utilizing whole-genome gene expression data from both mouse models and human cancer patients, we demonstrated that the expression profile of the mast cell-dependent genes differs between tumor and normal tissues from lung, breast, and colon, respectively. Mast cell infiltration is potentially increased in tumors compared with normal tissues, suggesting that mast cells might participate in tumor development. Accordingly, a prognostic molecular signature was developed based on the mast cell-dependent genes, which predicted recurrence-free survival for human patients with lung, breast, and colon cancers, respectively. Our study provides a novel transcriptomic insight into the impact of mast cells in the tumor microenvironment, though further experimental investigation is needed to validate the exact role of individual mast cell-dependent genes in different cancers.
迄今为止,由于关于肥大细胞浸润与癌症发生发展及预后之间关系的观察结果不一致,肥大细胞在肿瘤微环境中的确切影响仍存在争议。先前研究中的差异促使我们从不同角度研究肥大细胞在癌症病理学中的作用。在此,我们研究了肥大细胞对组织微环境中转录组图谱的影响。携带()突变的小鼠肥大细胞生成缺陷,被用于评估肥大细胞对基因表达的影响。通过检测野生型小鼠、小鼠以及移植了肥大细胞的小鼠的转录组图谱,我们确定了一系列“肥大细胞依赖性基因”,这些基因在癌症相关通路中富集。利用来自小鼠模型和人类癌症患者的全基因组基因表达数据,我们证明肥大细胞依赖性基因的表达谱在肺癌、乳腺癌和结肠癌的肿瘤组织与正常组织之间存在差异。与正常组织相比,肿瘤中肥大细胞浸润可能增加,这表明肥大细胞可能参与肿瘤发展。因此,基于肥大细胞依赖性基因开发了一种预后分子特征,分别预测了肺癌、乳腺癌和结肠癌人类患者的无复发生存率。我们的研究为肥大细胞在肿瘤微环境中的影响提供了新的转录组学见解,不过还需要进一步的实验研究来验证各个肥大细胞依赖性基因在不同癌症中的具体作用。