Clinicopathological significance of SPC18 in colorectal cancer: SPC18 participates in tumor progression

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide. In order to identify novel prognostic markers or therapeutic targets for CRC, we searched for candidate genes in our comprehensive gene expression libraries, and focused on SEC11A, which encodes the SPC18 protein. SPC18 plays a key role in the endoplasmic reticulum‐Golgi secretory pathway and presumably regulates the secretion of various secretory proteins. An immunohistochemical analysis of SPC18 in 137 CRC tissue samples demonstrated that 79 (58%) CRC cases were positive for SPC18. SPC18‐positive CRC cases were more advanced in terms of N classification (P = 0.0315) and tumor stage (P = 0.0240) than SPC18‐negative CRC cases. Furthermore, the expression of SPC18 was an independent prognostic classifier for CRC patients. The cell growth and invasiveness of SPC18 siRNA‐transfected CRC cell lines was less than that of the negative control siRNA‐transfected cell lines. The levels of phosphorylated epidermal growth factor receptor, Erk and Akt were lower in SPC18 siRNA‐transfected CRC cells than in control cells. The expression of SPC18 was colocalized with β‐catenin nuclear localization and MMP7 at the invasive front. An immunohistochemical analysis of human colorectal polyp specimens revealed a sequential increase in the expression of SPC18 through the conventional adenoma‐carcinoma pathway, while SPC18 was not expressed or was expressed to a lesser extent in serrated pathway‐related tumors. These results suggest that SPC18 is involved in tumor progression, and is an independent prognostic classifier in patients with CRC.

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

“…Two of these subunits, SPC18 and SPC21, are presumed to have catalytic activity [12], indicating that SPC18 overexpression induces TGF-α secretion. SPC18 overexpression is also associated with tumor progression in colorectal and urinary bladder cancer [13, 14]. These data support the notion that SPC18 protein may be a potential novel marker for a wide variety of malignancies.…”

Claspin overexpression is associated with high‐grade histology and poor prognosis in renal cell carcinoma

“…Univariate and multivariate Cox regression analyses were used to evaluate the associations between clinical covariates and survival as described previously. 23…”

“…Differences between the survival curves were tested for statistical significance by log‐rank test. Univariate and multivariate Cox regression analyses were used to evaluate the associations between clinical covariates and survival as described previously . A P value of less than 0.05 was considered to indicate statistical significance.…”

Long non-coding RNA DDX11-AS1 facilitates gastric cancer progression by regulating miR-873-5p/SPC18 axis

“…For example, overexpression of SEC11A promoted cell growth and invasiveness in bladder cancer [34]. Down-regulation of SPC18 inhibited cell proliferation and invasive activity in colorectal cancer through inactivation of EGFR signalling [35]. Also, SPC18 expression was up-regulated in GC tissues, and SPC18 overexpression facilitated GC malignant progression via inducing TGF-a secretion [36].…”