Clinicopathological significance of SPC18 in colorectal cancer: SPC18 participates in tumor progression.
Clinicopathological significance of SPC18 in colorectal cancer: SPC18 participates in tumor progression.
复制标题
SPC18在大肠癌中的临床病理学意义：SPC18参与肿瘤进展。
DOI：
10.1111/cas.13121
复制
发表时间：
2017-01
期刊：
影响因子：
5.7
通讯作者：
Yasui W
中科院分区：
文献类型：
--
作者：
Hattori T;Sentani K;Naohide O;Sakamoto N;Yasui W
结直肠癌（CRC）是全球癌症相关死亡的主要原因之一。为了鉴定新的CRC预后标志物或治疗靶点，我们在我们的综合基因表达文库中搜索候选基因，并将重点放在编码SPC 18蛋白的SEC 11 A上。SPC 18在内质网-高尔基体分泌途径中起关键作用，并可能调节各种分泌蛋白的分泌。对137例结直肠癌组织样本中SPC 18的免疫组化分析表明，79例（58%）结直肠癌病例为SPC 18阳性。SPC 18阳性CRC病例在N分类（P = 0.0315）和肿瘤分期（P = 0.0240）方面比SPC 18阴性CRC病例更先进。此外，SPC 18的表达是CRC患者的独立预后分类器。SPC 18 siRNA转染的CRC细胞系的细胞生长和侵袭力低于阴性对照siRNA转染的细胞系。SPC 18 siRNA转染的CRC细胞中磷酸化表皮生长因子受体、Erk和Akt的水平低于对照细胞。SPC 18的表达与β-catenin核定位和MMP 7在浸润前沿共定位。对人类结直肠息肉标本的免疫组织化学分析显示，SPC 18的表达通过传统的腺瘤-癌途径连续增加，而SPC 18在锯齿状途径相关肿瘤中不表达或表达程度较低。这些结果表明SPC 18参与肿瘤进展，并且是CRC患者的独立预后分类器。
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.