Objectives: Esophageal cancer is the sixth most common malignancy worldwide. Signal peptidase complex 18 (SPC18) protein, which is encoded by the SEC11A gene, is one of the subunits of the signal peptidase complex and plays an important role in the secretion of proteins including transforming growth factor α (TGF-α). In this study, we investigated the significance of SPC18 expression in human esophageal squamous cell carcinoma (ESCC). Methods: SPC18 expression was examined by immunohistochemistry. RNA interference was used to inhibit SPC18 expression in ESCC cell lines. To examine cell viability, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. The effects of SPC18 inhibition on epidermal growth factor receptor (EGFR) signaling were analyzed by Western blot. Results:In total, 46 (50%) of 92 ESCC cases were positive for SPC18. SPC18 staining was observed more frequently in stage II/III/IV cases than in stage I cases (p = 0.028). We found that SPC18 expression was significantly associated with increased cancer-specific mortality (p = 0.006, log-rank test). SPC18 expression was frequently found in EGFR-positive cases compared with EGFR-negative cases. Cell proliferation and EGFR signaling were inhibited by SPC18 knockdown. Conclusion: Specific inhibitors of SPC18 may be promising anticancer drugs for patients with ESCC.

中文翻译：

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SPC18 表达是食管鳞状细胞癌患者的独立预后指标

目的：食管癌是全球第六大常见恶性肿瘤。信号肽酶复合物 18 (SPC18) 蛋白由 SEC11A 基因编码，是信号肽酶复合物的亚基之一，在包括转化生长因子 α (TGF-α) 在内的蛋白质分泌中起重要作用。在这项研究中，我们调查了 SPC18 表达在人食管鳞状细胞癌 (ESCC) 中的意义。方法：通过免疫组织化学检查SPC18的表达。RNA干扰用于抑制ESCC细胞系中SPC18的表达。为了检查细胞活力，我们进行了 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑鎓化验。通过蛋白质印迹分析 SPC18 抑制对表皮生长因子受体 (EGFR) 信号传导的影响。结果：总共，92 例 ESCC 病例中有 46 例 (50%) SPC18 呈阳性。SPC18 染色在 II/III/IV 期病例中比在 I 期病例中更频繁地观察到 (p = 0.028)。我们发现 SPC18 表达与癌症特异性死亡率的增加显着相关（p = 0.006，对数秩检验）。与 EGFR 阴性病例相比，在 EGFR 阳性病例中经常发现 SPC18 表达。SPC18 敲低可抑制细胞增殖和 EGFR 信号传导。结论：SPC18的特异性抑制剂可能是ESCC患者有前景的抗癌药物。与 EGFR 阴性病例相比，在 EGFR 阳性病例中经常发现 SPC18 表达。SPC18 敲低可抑制细胞增殖和 EGFR 信号传导。结论：SPC18的特异性抑制剂可能是ESCC患者有前景的抗癌药物。与 EGFR 阴性病例相比，在 EGFR 阳性病例中经常发现 SPC18 表达。SPC18 敲低可抑制细胞增殖和 EGFR 信号传导。结论：SPC18的特异性抑制剂可能是ESCC患者有前景的抗癌药物。