Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Pathobiology. 2020;87(4):254-261. doi: 10.1159/000506956. Epub 2020 Jun 19.
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).
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.
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.
Specific inhibitors of SPC18 may be promising anticancer drugs for patients with ESCC.
食管癌是全球第六大常见恶性肿瘤。SEC11A 基因编码的信号肽酶复合物 18（SPC18）蛋白是信号肽酶复合物的一个亚基，在包括转化生长因子α（TGF-α）在内的蛋白质分泌中发挥重要作用。在本研究中，我们研究了 SPC18 表达在人食管鳞状细胞癌（ESCC）中的意义。
采用免疫组织化学法检测 SPC18 表达。采用 RNA 干扰抑制 ESCC 细胞系中的 SPC18 表达。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法检测细胞活力。采用 Western blot 分析 SPC18 抑制对表皮生长因子受体（EGFR）信号的影响。
共 92 例 ESCC 病例中，46 例（50%）SPC18 阳性。SPC18 染色在 II/III/IV 期病例中比 I 期病例更常见（p=0.028）。我们发现 SPC18 表达与癌症特异性死亡率增加显著相关（p=0.006，对数秩检验）。与 EGFR 阴性病例相比，SPC18 表达更常见于 EGFR 阳性病例。SPC18 敲低抑制细胞增殖和 EGFR 信号。
SPC18 的特异性抑制剂可能是 ESCC 患者有前途的抗癌药物。
