Jia Yunlong, Wang Hongyan, Wang Yu, Wang Tingting, Wang Miao, Ma Ming, Duan Yuqing, Meng Xianli, Liu Lihua
Department of Biotherapy, Fourth Hospital of Hebei Medical University and Hebei Cancer Institute, Shijiazhuang, China.
Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Int J Cancer. 2015 Sep 1;137(5):1095-106. doi: 10.1002/ijc.29481. Epub 2015 Apr 28.
Indoleamine 2,3-dioxygenase (IDO) has been reported to be involved in esophageal squamous cell cancer (ESCC) progression by promoting immune escape. Previous studies have revealed bridging integrator-1 (Bin1) can inhibit cancer cell growth by suppressing expression of IDO, thus we investigated the correlation between the expression of Bin1 and IDO and their prognostic significances for ESCC patients. Specimens were collected from 196 ESCC patients and detected with flow cytometry, reverse transcription-polymerase chain reaction and immunohistochemistry. We found that in tumor microenvironment (TME) and tumor draining lymph node (TDLN), the proportions of CD3(+) CD4(+) T cell, CD3(+) CD8(+) T cell and CD3(-) CD16(+) CD56(+) NK cell were lower while the proportions of CD3(-) CD19(+) B cell and CD4(+) CD25(+) Treg were higher in specimens with high IDO expression when compared to the specimens with low IDO expression (p < 0.01). In addition, IDO expression was negatively correlated with Bin1 expression at gene and protein level in TME and TDLN. Both the expression of Bin1 and IDO were associated with some clinicopathological parameters including differentiation grade, TNM stage, invasion range, lymph node metastasis (p < 0.05). Moreover, multivariate survival analysis suggested that, along with some other parameters, low expression of Bin1 and high expression of IDO might be independent prognostic factor for ESCC patients. Our results demonstrate that low expression of Bin1, along with high expression of IDO, are predictor for poor prognosis in ESCC and thereby could be used to establish new therapeutic strategies.
据报道,吲哚胺2,3-双加氧酶(IDO)通过促进免疫逃逸参与食管鳞状细胞癌(ESCC)的进展。先前的研究表明,桥联整合因子-1(Bin1)可通过抑制IDO的表达来抑制癌细胞生长,因此我们研究了Bin1和IDO表达之间的相关性及其对ESCC患者的预后意义。收集了196例ESCC患者的标本,并通过流式细胞术、逆转录-聚合酶链反应和免疫组织化学进行检测。我们发现,在肿瘤微环境(TME)和肿瘤引流淋巴结(TDLN)中,与低IDO表达的标本相比,高IDO表达标本中CD3(+) CD4(+) T细胞、CD3(+) CD8(+) T细胞和CD3(-) CD16(+) CD56(+) NK细胞的比例较低,而CD3(-) CD19(+) B细胞和CD4(+) CD25(+) Treg的比例较高(p < 0.01)。此外,在TME和TDLN中,IDO表达在基因和蛋白质水平上与Bin1表达呈负相关。Bin1和IDO的表达均与一些临床病理参数相关,包括分化程度、TNM分期、浸润范围、淋巴结转移(p < 0.05)。此外,多因素生存分析表明,与其他一些参数一起,Bin1低表达和IDO高表达可能是ESCC患者的独立预后因素。我们的结果表明,Bin1低表达与IDO高表达是ESCC预后不良的预测指标,因此可用于制定新的治疗策略。