A novel tumor-based epithelial-to-mesenchymal transition score that associates with prognosis and metastasis in patients with Stage II/III colorectal cancer
A novel tumor-based epithelial-to-mesenchymal transition score that associates with prognosis and metastasis in patients with Stage II/III colorectal cancer
复制标题
DOI：
10.1002/ijc.31739
复制
发表时间：
2019-01-01
影响因子：
6.4
通讯作者：
Roxburgh, C. S.
中科院分区：
文献类型：
--
作者：
Roseweir, A. K.;Kong, C. Y.;Roxburgh, C. S.
越来越多的人认识到，肿瘤中心和微环境中的宿主因素在决定结直肠癌(CRC)预后方面发挥着关键作用。因此，转移过程现在被定义为上皮-间充质转化(EMT)的结果。明确EMT在肿瘤中心的作用及其对肿瘤微环境的影响，将有利于结直肠癌的预后和治疗干预。本研究在185例II/III期结直肠癌患者组织芯片上评估了肿瘤中心内的五个免疫组织化学EMT标记。在185例结直肠癌患者中，胞浆蜗牛(HR 1.94 95%可信区间1.15-3.29，p=0.012)和新的联合EMT评分(HR 3.86 95%CI 2.17-6.86，p<；0.001)与肿瘤特异性生存率降低有关。联合的EMT评分还与肿瘤萌发(p=0.046)和全身炎症(p=0.007)以及间质(p=0.030)和侵袭边缘(p=0.035)记忆T细胞减少有关。此外，联合EMT评分与肿瘤特异性生存期无关(HR 4.12，95%CI 2.30-7.39，p<；0.001)。总之，一种新的联合EMT评分对II/III期结直肠癌患者的生存进行分层，并与肿瘤转移的关键因素相关联。因此，结合EMT评分可以用来确定有微转移风险的患者，以及谁可能受益于标准辅助治疗，可能与EMT阻断相结合。
It is increasingly appreciated that host factors within the tumor center and microenvironment play a key role in dictating colorectal cancer (CRC) outcomes. As a result, the metastatic process has now been defined as a result of epithelial-mesenchymal transition (EMT). Establishment of the role of EMT within the tumor center and its effect on the tumor microenvironment would be beneficial for prognosis and therapeutic intervention in CRC. The present study assessed five immunohistochemical EMT markers within the tumor center on a 185 Stage II/III CRC patient tissue microarray. In 185 patients with CRC, cytoplasmic snail (HR 1.94 95% confidence interval [CI] 1.15-3.29, p = 0.012) and a novel combined EMT score (HR 3.86 95% CI 2.17-6.86, p < 0.001) were associated with decreased cancer-specific survival. The combined EMT score was also associated with increased tumor budding (p = 0.046), and systemic inflammation (p = 0.007), as well as decreased memory T-cells within the stroma (p = 0.030) and at the invasive margin (p = 0.035). Furthermore, the combined EMT score was associated with cancer-specific survival independent of TNM-stage (HR 4.12 95% CI 2.30-7.39, p < 0.001). In conclusion, a novel combined EMT score stratifies patient's survival in Stage II/III CRC and associates with key factors of tumor metastasis. Therefore, the combined EMT score could be used to identify patients at risk of micrometastases and who may benefit from standard adjuvant therapy, potentially in combination with EMT blockade.