Abstract
BackgroundMetastasis-associated in colon cancer 1 (MACC1) has been reported to promote tumor cell invasion and metastasis. Cancer stem cells and epithelial-mesenchymal transition (EMT) have also been reported to promote tumor cell proliferation, invasion, and metastasis. KiSS-1, a known suppressor of metastasis, has been reported to be down-regulated in various tumors. However, the associations of MACC1, CD44, Twist1, and KiSS-1 in colonic adenocarcinoma (CAC) invasion and metastasis remain unclear. The purpose of this study is to investigate the roles of MACC1, CD44, Twist1, and KiSS-1 in CAC invasion and metastasis and their associations with each other and with the clinicopathological characteristics of CAC patients.MethodsImmunohistochemistry and multivariate analysis were carried out to explore the expression of MACC1, CD44, Twist1, and KiSS-1 in 212 whole-CAC-tissue specimens and the corresponding normal colon mucosa tissues. Demographic, clinicopathological, and follow-up data were also collected.ResultsThe results of this study showed MACC1, CD44, and Twist1 expression to be up-regulated, and KiSS-1 expression was down-regulated in CAC tissues. Positive expression of MACC1, CD44, and Twist1 was found to be positively correlated with invasion, tumor grades, and lymph- node-metastasis (LNM) stages and tumor-node-metastasis (TNM) stages for patients with CAC. Positive expression of KiSS-1 was inversely associated with invasion, tumor size, LNM stage, and TNM stage. The KiSS-1-positive expression group had significantly more favorable OS than did the KiSS-1-negative group. Univariate analysis indicated that overexpression of MACC1, CD44, and Twists1 was negatively associated with longer overall survival (OS) time, and there was a positive relationship between KiSS-1-positive expression and OS time for patients with CAC. Multivariate Cox analysis demonstrated that overexpression of MACC1, CD44, Twist1, and low expression of KiSS-1 and LNM and TNM stages were independent predictors of prognosis in patients with CAC.ConclusionsThe results in this study indicated that levels of expression of MACC1, CD44, Twist1, and KiSS-1 are related to the duration of OS in patients with CAC. MACC1, CD44, Twist1, and KiSS-1 may be suitable for use as biomarkers and therapeutic targets in CAC.
Highlights
Metastasis-associated in colon cancer 1 (MACC1) has been reported to promote tumor cell invasion and metastasis
The immunostaining results indicated that positive expression of MACC1 in colonic adenocarcinoma (CAC) was positively correlated with invasion, tumor differentiation, lymph- node-metastasis (LNM) stages, and TNM stages (Table 2)
The results demonstrated that positive expression of CD44 in CAC was positively correlated with invasion, tumor differentiation, LNM stages, and TNM stages (Table 2)
Summary
Metastasis-associated in colon cancer 1 (MACC1) has been reported to promote tumor cell invasion and metastasis. Cancer stem cells and epithelial-mesenchymal transition (EMT) have been reported to promote tumor cell proliferation, invasion, and metastasis. The associations of MACC1, CD44, Twist, and KiSS-1 in colonic adenocarcinoma (CAC) invasion and metastasis remain unclear. The most common causes of cancer treatment failure are relapse and metastasis This may be related to an oncogene called metastasis-associated in colon cancer 1 (MACC1). MACC1 is reported to promote tumor cell proliferation, invasion, and dissemination by inducing epithelial-mesenchymal transition (EMT) in vitro [5, 6] and to induce tumor cell growth, invasion, and metastasis in vivo [3, 7]. It has been demonstrated that MACC1 should be defined as a prognostic and metastatic biomarker for various cancers [8]
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