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JNK1 和 VDR 的基质表达与食管鳞状细胞癌的预后相关。

Stromal expression of JNK1 and VDR is associated with the prognosis of esophageal squamous cell carcinoma.

机构信息

Department of Pathology and Institute of Precision Medicine, Jining Medical University, 16 Hehua Road, Jining, 272067, China.

Department of Pathology, Xinxiang Medical University, Xinxiang, China.

出版信息

Clin Transl Oncol. 2018 Sep;20(9):1185-1195. doi: 10.1007/s12094-018-1843-2. Epub 2018 Feb 8.

DOI:10.1007/s12094-018-1843-2
PMID:29423673
Abstract

PURPOSE

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, and its outcome is poor. The purpose of this study was to determine the association between JNK1 and vitamin D receptor (VDR) expression and the prognosis of ESCC.

METHODS

Immunohistochemical staining was conducted on ESCC tissue microarrays (362 pairs of ESCC and normal esophagus tissues). The epithelial and stromal expression levels of c-jun NH2-terminal kinase 1 (JNK1) and VDR were scored and correlated with the ESCC characteristics. Laser-capture-based quantitative RT-PCR was performed on ESCC tissues. The effects of JNK1 and VDR on ESCC cell proliferation and migration were analyzed in vitro by transient transfection, and protein changes were evaluated by immunoblotting.

RESULTS

Both JNK1 and VDR were reduced in ESCC epithelial cells in comparison with the normal esophagus, but the expression of JNK1 and VDR in ESCC stromal tissues, not epithelial cells, was strongly associated with the survival time of ESCC patients. Functional studies showed that increased JNK1 suppressed cancer cell proliferation, mobility, and migration, which were linked to the alterations of VDR and metastasis-associated proteins.

CONCLUSION

JNK1 and VDR act as tumor suppressors, and their stromal expression levels are associated with prognosis in esophageal squamous cell carcinoma.

摘要

目的

食管鳞状细胞癌(ESCC)是全球最常见的癌症之一,其预后较差。本研究旨在确定 JNK1 和维生素 D 受体(VDR)表达与 ESCC 预后之间的关联。

方法

对 ESCC 组织微阵列(362 对 ESCC 和正常食管组织)进行免疫组织化学染色。对 c-jun NH2-末端激酶 1(JNK1)和 VDR 的上皮和基质表达水平进行评分,并与 ESCC 特征相关联。对 ESCC 组织进行基于激光捕获的定量 RT-PCR。通过瞬时转染在体外分析 JNK1 和 VDR 对 ESCC 细胞增殖和迁移的影响,并通过免疫印迹评估蛋白质变化。

结果

与正常食管相比,JNK1 和 VDR 在 ESCC 上皮细胞中均降低,但 ESCC 基质组织中 JNK1 和 VDR 的表达,而不是上皮细胞,与 ESCC 患者的生存时间密切相关。功能研究表明,增加的 JNK1 抑制了癌细胞的增殖、迁移和迁移,这与 VDR 和转移相关蛋白的改变有关。

结论

JNK1 和 VDR 作为肿瘤抑制因子,其在食管鳞状细胞癌中的基质表达水平与预后相关。

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