Zhao Tiancheng, Li Yezhou, Zhang Jiayu, Zhang Bin
Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Oncol Lett. 2020 Aug;20(2):1127-1134. doi: 10.3892/ol.2020.11647. Epub 2020 May 20.
PD-L1 inhibitors are widely used in tumor immunotherapy, but their mechanism in colorectal cancer remains unclear. The present study aimed to investigate the mechanisms underlying programmed death ligand 1 (PD-L1) regulation via the interferon-γ (IFN-γ)/janus kinase (JAK)/STAT signaling pathway, and its prognostic value in patients with colorectal cancer (CRC). A cohort of 181 patients were recruited to determine the association between PD-L1 expression and CRC prognosis; the patients were newly diagnosed with colorectal adenocarcinoma and had also undergone a physical tumorectomy. Immunohistochemical staining and survival analysis were used to evaluate the predictive value of PD-L1 protein expression in CRC. Gene set enrichment analysis, RT-qPCR and western blotting, etc were performed to confirm that PD-L1 is regulated by the IFN-γ/JAK/STAT signaling pathway. PD-L1 up-regulation was more frequently observed in patients with larger tumors, positive vascular or lymphatic infiltration and a poorly differentiated stage in addition to being associated with a poor survival in patients with CRC. Following the stimulation with IFN-γ, PD-L1 expression levels were revealed to be increased via the JAK2/STAT1 signaling pathway. In conclusion, the findings of the present study indicated that the expression levels of PD-L1 may be associated with a poor prognosis in patients with CRC. In addition, the results suggested that the IFN-γ-mediated overexpression of PD-L1 in CRC cells may be regulated by the JAK2/STAT1 signaling pathway.
程序性死亡受体 1 配体（PD-L1）抑制剂广泛应用于肿瘤免疫治疗，但其在结直肠癌中的作用机制尚不清楚。本研究旨在探讨通过干扰素-γ（IFN-γ）/ Janus 激酶（JAK）/信号转导和转录激活因子（STAT）信号通路调控程序性死亡配体 1（PD-L1）的机制及其在结直肠癌（CRC）患者中的预后价值。招募了 181 例患者以确定 PD-L1 表达与 CRC 预后之间的关联；这些患者为新诊断的结肠腺癌患者且均接受了实体肿瘤切除术。采用免疫组织化学染色和生存分析评估 PD-L1 蛋白表达在 CRC 中的预测价值。进行基因集富集分析、逆转录-定量聚合酶链反应（RT-qPCR）和蛋白质印迹法等以证实 PD-L1 受 IFN-γ/JAK/STAT 信号通路调控。除了与 CRC 患者的不良生存相关外，在肿瘤较大、有血管或淋巴浸润阳性以及分化程度差的患者中更常观察到 PD-L1 上调。在用 IFN-γ刺激后，发现 PD-L1 表达水平通过 JAK2/STAT1 信号通路升高。总之，本研究结果表明，PD-L1 的表达水平可能与 CRC 患者的不良预后相关。此外，结果表明 CRC 细胞中 IFN-γ介导的 PD-L1 过表达可能受 JAK2/STAT1 信号通路调控。
