Gu Jiangning, Gao Feng, Fan Bin, Xu Shiqi, Luo Haifeng, Zhang Jie, Jiang Qi, Wang Chenqi, Tan Guang, Qi Wenjing, Du Jian, Huang Siqian, Sun Xiaohong, Chen Dan
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Department of Digestive Endoscopy, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
J Oncol. 2023 Mar 6;2023:7971306. doi: 10.1155/2023/7971306. eCollection 2023.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis; nearly 80% patients have regional or distant metastasis when diagnosed. Tumor microenvironment (TME) alteration and epithelial-to-mesenchymal transition (EMT) have been reported to play a key role in cancer metastasis. However, the correlation between TME and EMT was poorly studied in PDAC. This study aims to explore the correlation between EMT markers and TME alteration, mainly including macrophage polarization and PD-L1 expression change, in primary and metastatic PDAC tissues by immunohistochemistry. The results indicated that macrophage polarization was found in metastases with the number of M1 macrophages (CD86) decreased and M2 (CD163) increased, though PD-L1 expression did not have a significant alteration. Compared to primary tumors, E-cadherin was significantly lower, while snail was higher, while no difference was found with N-cadherin and ZEB1. Correlation analysis indicated that snail, but not ZEB1, E-cadherin, or N-cadherin, was highly correlated with macrophage polarization. To conclude, the number of CD86 M1 macrophages was increased while CD163 M2 macrophages decreased in metastases, with no significant alteration of PD-L1 expression compared to primary tumors. EMT markers-Snail and E-cadherin-but not ZEB1 or N-cadherin, were found to be higher/lower in metastases, which mean that EMT played an important role in PDAC metastasis. Further analysis indicated that snail was highly correlated with M1 to M2 macrophage polarization, which prompted that EMT may be one reason for macrophage polarization induced TME alteration in PDAC metastasis.
胰腺导管腺癌（PDAC）是一种侵袭性很强的恶性肿瘤，预后较差；近80%的患者在确诊时已有局部或远处转移。肿瘤微环境（TME）改变和上皮-间质转化（EMT）在癌症转移中起关键作用。然而，在PDAC中，TME与EMT之间的相关性研究较少。本研究旨在通过免疫组织化学探讨原发性和转移性PDAC组织中EMT标志物与TME改变之间的相关性，主要包括巨噬细胞极化和PD-L1表达变化。结果表明，在转移灶中发现了巨噬细胞极化，M1巨噬细胞（CD86）数量减少，M2（CD163）数量增加，尽管PD-L1表达没有显著改变。与原发性肿瘤相比，E-钙黏蛋白显著降低，而Snail升高，而N-钙黏蛋白和ZEB1没有差异。相关性分析表明，与ZEB1、E-钙黏蛋白或N-钙黏蛋白不同，Snail与巨噬细胞极化高度相关。总之，与原发性肿瘤相比，转移灶中CD86 M1巨噬细胞数量增加，而CD163 M2巨噬细胞数量减少，PD-L1表达无显著改变。EMT标志物——Snail和E-钙黏蛋白——而非ZEB1或N-钙黏蛋白，在转移灶中升高/降低，这意味着EMT在PDAC转移中起重要作用。进一步分析表明，Snail与M1到M2巨噬细胞极化高度相关，这提示EMT可能是PDAC转移中巨噬细胞极化诱导TME改变的一个原因。
