Abstract 522: Expression and functional analysis of signal peptidase complex 18 in bladder cancer

Abstract

Abstract Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. In the present study, we built an in-house oligonucleotide array, on which 394 genes were selected based on our SAGE data and previously reported array data, in order to identify the genes of most relevance to gastric carcinogenesis. Among these genes, we focused on SEC11A, because it is frequently overexpressed in gastric cancer (GC). SEC11A encodes the SPC18 protein, which is one of the subunits of the signal peptidase complex (SPC). Most secretory proteins contain amino terminal- or internal signal peptides that direct their sorting to the endoplasmic reticulum (ER). From the ER, proteins are transported to either the extracellular space or the plasma membrane through the ER-Golgi secretory pathway. The ER signal peptides are then cleaved by the SPC. In GC, SPC18 contributes to progression via EGFR pathway associated with TGF-a secretion. However, the expression and function of SPC18 have not been investigated in bladder cancer (BC). In this study, we analyzed the expression and distribution of SPC18 in human BC. Expression of SPC18 was observed in 44 (54.3%) out of 81 BC cases that was associated with T category (p=0.0002), Grade (p=0.0425), vascular invasion (p=0.0112) and CK5/6 positive/ CK20 negative basal type BC (p=0.0004). The univariate analysis indicated that expression of SPC18 (HR, 3.14; 95% CI, 1.47-7.47; P=0.0027) was associated with overall survival. In the multivariate model, SPC18 expression was an independent prognostic indicator (HR, 3.46; 95% CI, 1.35-10.00; P=0.0087). BC cells KMBC2 transfected with SPC18 expression vector significantly induced the cell growth (p<0.01) and invasion (p<0.01) activity. Western blot showed the overexpression of SPC18 induced the phosphorylation of EGFR, Akt and Erk. Real-time reverse transcription PCR analysis revealed the SPC18 forced expression cells induced mesenchymal character. These results suggest that SPC18 might contribute to the progression of BC. Citation Format: Yoshinori Shigematsu, Yohei Sekino, Naoya Sakamoto, Kazuhiro Sentani, Naohide Oue, Tetsutaro Hayashi, Jun Teishima, Akio Matsubara, Wataru Yasui. Expression and functional analysis of signal peptidase complex 18 in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 522. doi:10.1158/1538-7445.AM2017-522