SPC18 Expression Is an Independent Prognostic Indicator of Patients with Esophageal Squamous Cell Carcinoma

Abstract

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.

MiR‐873‐5p modulates progression of tongue squamous cell carcinoma via targeting SEC11A

“…The activated EGFR/ERK1/2 would also induce the EMT process to promote the development of head and neck squamous cell carcinoma (Gao et al., 2018). At the meantime, Yuji Yamamoto et al demonstrated the elevated SPC18 in the EGFR‐positive esophageal cancer patients, while inhibiting SPC18 can reduce the activity of EGFR with the decreased phosphorylation of Akt and Erk (Yamamoto et al., 2020). By contrast, overexpression of SPC18 can enhance the phosphorylation of EGFR, Akt, and ERK1/2, thus promoting the proliferation of bladder cancer cells (Shigematsu et al., 2019).…”

“…The inhibition of lncRNA DDX11‐AS1 was shown to suppress the growth of gastric cancer cells through upregulating miR‐873‐5p to reduce the expression of SPC18 (Ren et al., 2020). SPC18 was also increased in the esophageal cancer tissues, which served as an indicator for the independent prognosis in the work from Yuji Yamamoto et al, and more importantly, silencing SPC18 may limit the activity of EGFR pathway and the proliferation of esophageal cancer cells (Yamamoto et al., 2020). Nevertheless, there remains no sufficient evidence suggesting the involvement of miR‐873‐5p in TSCC by targeting SEC11A .…”

Pan-cancer analysis identifies SEC11A as an immunological and prognostic biomarker

“…Interestingly, study found that high SEC11A expression was examined in squamous cell carcinoma of tongue and its activation induced proliferation, migration, and invasion in tongue squamous cell carcinoma cells [7]. SEC11A up-regulation is in relation to increased cancer-specific mortality among esophageal squamous cell carcinoma [8]. Moreover, SEC11A knockdown weakens cell proliferation as well as EGFR signaling in esophageal squamous cell carcinoma.…”

Signal peptidase complex catalytic subunit SEC11A upregulation is a biomarker of poor prognosis in patients with head and neck squamous cell carcinoma

“…SEC11A can promote the phosphorylation of epidermal growth factor receptor (EGFR) and the downstream extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) in colorectal cancer cells [ 3 ]. Its expression serves as an independent prognostic biomarker for patients with CRC [ 3 ], basal-Like bladder cancer [ 4 ] and esophageal squamous cell carcinoma [ 5 ]. One recent study found that inhibiting SEC11A can reduce proliferation, migration, and invasion and induce apoptosis of tongue squamous cell carcinoma [ 6 ], suggesting a potential oncogenic role of this gene in head and neck squamous cell carcinoma.…”