Song Wenqing, Wang Xiaolin, Yang Ruixue, Wu Shiwu, Wang Danna
Department of Pathology, The First Affiliated Hospital of Bengbu Medical University Anhui, China.
Department of Pathology, Bengbu Medical University Anhui, China.
Int J Clin Exp Pathol. 2019 Mar 1;12(3):987-995. eCollection 2019.
Metastasis-associated in colon cancer-1 (MACC1) is a key transcriptional regulator of mesenchymal-epithelial transition (MET) gene and so involved in the hepatocyte growth factor/MET signaling pathway. Snail has been reported to be associated with tumor epithelial-mesenchymal transition (EMT) and involved in the process of invasion and metastasis. KAI1 is a suppressor gene of tumor metastasis. The aim of this study is to explore the associations of MACC1, Snail, and KAI1 expression in esophageal squamous cell carcinoma (ESCC) and clinicopathologic characteristics of ESCC patients and their associations with each other.
Immunohistochemistry was conducted to detect the expression of MACC1, Snail, and KAI1 in 214 whole-ESCC-tissue samples and corresponding normal esophageal mucosa tissues. All clinicopathologic, demographic, and follow-up data were collected.
MACC1 and Snail were significantly up-regulated in ESCC samples when compared with control samples; KAI1 was significantly down-regulated in ESCC group when compared with control group. Furthermore, positive expression of MACC1 and Snail was positively associated with tumor stages, lymph-node-metastasis (LNM) stages, and tumor-node-metastasis (TNM) stages. Positive expression of KAI1 was negatively associated with tumor grade, tumor stage, and LNM stages as well as TNM stage. The MACC1- or Snail-positive expression group had more unfavorable overall survival (OS) time than did the MACC1- or Snail-negative group; the positive expression of KAI1 group had significantly longer OS time than did the KiSS-1 negative group. Multivariate analysis of OS showed that overexpression of MACC1 and Snail, and down expression of KAI1 and tumor stages as well as TNM stages were independent prognostic factors for patients with ESCC.
Levels of expression of MACC1, Snail, and KAI1 are associated with the duration of OS in patients with ESCC. MACC1, Snail, and KAI1 should be considered as useful biomarkers and therapeutic targets in ESCC.
结肠癌转移相关蛋白1(MACC1)是间充质-上皮转化(MET)基因的关键转录调节因子,参与肝细胞生长因子/MET信号通路。据报道,Snail与肿瘤上皮-间质转化(EMT)相关,并参与侵袭和转移过程。KAI1是肿瘤转移抑制基因。本研究旨在探讨MACC1、Snail和KAI1在食管鳞状细胞癌(ESCC)中的表达及其与ESCC患者临床病理特征的关系,以及它们之间的相互关系。
采用免疫组织化学法检测214例ESCC全组织样本及相应正常食管黏膜组织中MACC1、Snail和KAI1的表达。收集所有临床病理、人口统计学和随访数据。
与对照样本相比,ESCC样本中MACC1和Snail显著上调;与对照组相比,ESCC组KAI1显著下调。此外,MACC1和Snail的阳性表达与肿瘤分期、淋巴结转移(LNM)分期和肿瘤-淋巴结-转移(TNM)分期呈正相关。KAI1的阳性表达与肿瘤分级、肿瘤分期、LNM分期以及TNM分期呈负相关。MACC1或Snail阳性表达组的总生存期(OS)时间比MACC1或Snail阴性组更差;KAI1阳性表达组的OS时间明显长于KAI1阴性组。OS的多因素分析表明,MACC1和Snail的过表达、KAI1的低表达以及肿瘤分期和TNM分期是ESCC患者的独立预后因素。
MACC1、Snail和KAI1的表达水平与ESCC患者的OS持续时间相关。MACC1、Snail和KAI1应被视为ESCC有用的生物标志物和治疗靶点。