OTX1 的过表达促进了食管鳞状细胞癌患者的肿瘤发生。
Overexpression of OTX1 promotes tumorigenesis in patients with esophageal squamous cell carcinoma.
机构信息
State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Shaanxi University of Chinese Medicine, Xi'an, China.
出版信息
Pathol Res Pract. 2022 Apr;232:153841. doi: 10.1016/j.prp.2022.153841. Epub 2022 Mar 11.
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is a multifactorial disease and the sixth leading cause of death from cancer worldwide. Patients with ESCC usually have a short survival period due to the late stage at diagnosis. Incidence rates of ESCC remain high among the elderly. With recent advances, it has been demonstrated that ESCC tumors display a unique genetic profile. This study aimed to examine the possible function of OTX1 in ESCC.
METHODS
We collected paraffin-embedded tumor tissues from 107 patients originally diagnosed with ESCC at Xijing Hospital and fresh-harvested and paired adjacent normal esophageal tissues from 15 ESCC patients undergoing curative resection. The expression level of OTX1 was evaluated through immunohistochemistry and western blot. Prognostic and survival analyses were conducted using univariate/multivariate analysis and log-rank analysis with SPSS 23.0. Cell models and xenograft models were used to examine the overexpression of OTX1 in vivo and in vitro.
RESULTS
OTX1 was overexpressed in ESCC tissues compared with normal esophageal tissues. Both the mRNA expression level and protein level of OTX1 were higher than they were in paired normal tissue. Prognostic and OS analyses showed that the OTX1 expression level was an individual prognostic factor in ESCC patients. Cell viability was significantly promoted when OTX1 was overexpressed in ESCC cell, Furthermore, downregulating OTX1 in EC109 cell significantly attenuated the cell proliferation migration and invasion. Flow cytometric detection showed that cells overexpressing OTX1 were predominantly in the S and G2&M phases. In the xenograft model, both tumor size and weight in the OTX1 overexpression group were significantly larger than those in the control group.
CONCLUSION
OTX1 is an independent prognostic factor of ESCC and contributes to tumorigenesis both in vivo and in vitro.
背景
食管鳞状细胞癌(ESCC)是一种多因素疾病,是全球第六大癌症死亡原因。由于诊断时已处于晚期,ESCC 患者的生存期通常较短。ESCC 的发病率在老年人中仍然很高。随着最近的进展,已经证明 ESCC 肿瘤具有独特的遗传特征。本研究旨在研究 OTX1 在 ESCC 中的可能作用。
方法
我们收集了 107 例在西京医院最初诊断为 ESCC 的患者的石蜡包埋肿瘤组织,以及 15 例接受根治性切除的 ESCC 患者新鲜采集的配对相邻正常食管组织。通过免疫组织化学和 Western blot 评估 OTX1 的表达水平。使用 SPSS 23.0 进行单变量/多变量分析和对数秩分析进行预后和生存分析。使用细胞模型和异种移植模型在体内和体外检查 OTX1 的过表达。
结果
与正常食管组织相比,OTX1 在 ESCC 组织中过表达。OTX1 的 mRNA 表达水平和蛋白水平均高于配对正常组织。预后和 OS 分析表明,OTX1 表达水平是 ESCC 患者的个体预后因素。当 ESCC 细胞中过表达 OTX1 时,细胞活力明显增强。此外,下调 EC109 细胞中的 OTX1 显著减弱了细胞增殖、迁移和侵袭。流式细胞术检测显示,过表达 OTX1 的细胞主要处于 S 和 G2&M 期。在异种移植模型中,OTX1 过表达组的肿瘤大小和重量明显大于对照组。
结论
OTX1 是 ESCC 的独立预后因素,在体内和体外均有助于肿瘤发生。