Interleukin-34 expression in ovarian cancer: a possible correlation with disease progression
Interleukin-34 expression in ovarian cancer: a possible correlation with disease progression
复制标题
DOI：
10.1093/intimm/dxz074
复制
发表时间：
2020-03-01
影响因子：
4.4
通讯作者：
Seino, Ken-Ichiro
中科院分区：
文献类型：
--
作者：
Endo, Hiraku;Hama, Naoki;Seino, Ken-Ichiro
卵巢癌是第二大致命的妇科恶性肿瘤，也是世界各地妇女癌症相关死亡的第七大常见原因。大多数卵巢癌患者被诊断为晚期，并在初次细胞减灭术和标准一线化疗后复发。因此，卵巢癌患者的成功管理需要确定导致进展和复发的因素。白细胞介素-34（IL-34）是一种新型细胞因子，是集落刺激因子-1受体（CSF-1 R）的组织特异性配体。在癌症中，IL-34发挥促肿瘤发生功能，促进肿瘤生长、转移、血管生成、免疫抑制和治疗抗性。在这项研究中，我们评估了IL-34对卵巢癌患者进展和生存的影响。首先，发现IL-34在几种人卵巢癌细胞系和患者的癌组织中表达。IL-34在卵巢癌细胞系和化疗患者的癌组织中的表达被细胞毒化疗增强。重要的是，高IL-34表达与不同队列中更差的无进展生存期（PFS）和总生存期相关。基于IL 34表达与其他相关基因如CSF 1 R和CD 163之间的组合的PFS评估与单独IL 34相比有助于进一步达到更大的统计学显著性。此外，在鼠卵巢癌细胞HM-1体内模型中，表明IL-34衍生的肿瘤细胞通过调节免疫环境与肿瘤进展和存活相关。总的来说，这些发现表明IL-34表达与卵巢癌患者和小鼠模型中的疾病进展之间可能存在相关性。
Ovarian cancer is the second-most lethal gynecological malignancy and the seventh-commonest cause of cancer-related death in women around the world. Most of the ovarian cancer patients are diagnosed at advanced stages and suffer from recurrence after primary cytoreductive surgery and standard first-line chemotherapy. Thus, the successful management of ovarian cancer patients requires the identification of factors that contribute to progression and relapse. Interleukin-34 (IL-34) is a novel cytokine that acts as a tissue-specific ligand of colony-stimulating factor-1 receptor (CSF-1R). In cancer, IL-34 exerts pro-tumorigenic functions that promote tumor growth, metastasis, angiogenesis, immune suppression and therapeutic resistance. In this study, we evaluate the impact of IL-34 on progression and survival of ovarian cancer patients. First, IL-34 was found to be expressed in several human ovarian cancer cell lines and cancer tissues from patients. The expression of IL-34 was enhanced by cytotoxic chemotherapy in ovarian cancer cell lines and cancer tissues from chemotherapy-treated ovarian cancer patients. Importantly, high IL-34 expression correlated with worse progression-free survival (PFS) and overall survival in different cohorts. The assessment of PFS based on a combination between IL34 expression and other related genes such as CSF1R and CD163 helped further to reach more statistical significance compared with IL34 alone. Furthermore, in the murine ovarian cancer cell HM-1 in vivo model, it was suggested that IL-34-derived tumor cells was correlated with tumor progression and survival by modulating the immune environment. Collectively, these findings indicate a possible correlation between IL-34 expression and disease progression in ovarian cancer patients and the mouse model.