Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Ann Surg Oncol. 2021 Oct;28(11):6424-6436. doi: 10.1245/s10434-021-09752-y. Epub 2021 Mar 12.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent chloride (Cl) anion conducting channel, and its role in esophageal squamous cell carcinoma (ESCC) was examined in the present study.
Overexpression experiments were conducted on human ESCC cell lines following the transfection of a CFTR plasmid, and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. A microarray analysis was performed to examine gene expression profiles. Fifty-three primary tumor samples collected from ESCC patients during esophagectomy were subjected to an immunohistochemical analysis.
Transfection of the CFTR plasmid into the ESCC KYSE 170 and KYSE 70 cell lines suppressed cell proliferation, migration, and invasion and induced apoptosis. The microarray analysis showed the up-regulated expression of genes involved in the p38 signaling pathway in CFTR plasmid-transfected KYSE 170 cells. Immunohistochemical staining revealed a relationship between the CFTR expression pattern at the invasive front and the pN category. A relationship was also observed between the weak expression of CFTR at the invasive front and a shorter postoperative survival in a prognostic analysis.
The overexpression of CFTR in ESCC activated the p38 signaling pathway and was associated with a good patient prognosis. These results indicate the potential of CFTR as a mediator of and/or a biomarker for ESCC.
囊性纤维化跨膜电导调节因子（CFTR）是一种 cAMP 依赖性氯离子（Cl）阴离子传导通道，本研究探讨了其在食管鳞状细胞癌（ESCC）中的作用。
通过转染 CFTR 质粒，在人 ESCC 细胞系中进行过表达实验，评估细胞增殖、细胞周期、凋亡、迁移和侵袭的变化。进行微阵列分析以检查基因表达谱。对 53 例 ESCC 患者手术切除的原发性肿瘤样本进行免疫组织化学分析。
CFTR 质粒转染 ESCC KYSE 170 和 KYSE 70 细胞系可抑制细胞增殖、迁移和侵袭，并诱导细胞凋亡。微阵列分析显示 CFTR 质粒转染的 KYSE 170 细胞中 p38 信号通路相关基因表达上调。免疫组织化学染色显示，侵袭前沿 CFTR 的表达模式与 pN 分类之间存在相关性。预后分析表明，侵袭前沿 CFTR 表达较弱与术后生存时间较短有关。
ESCC 中 CFTR 的过表达激活了 p38 信号通路，并与良好的患者预后相关。这些结果表明 CFTR 作为 ESCC 的介质和/或生物标志物具有潜在的应用价值。
