The aberrant expressions of MACC1, ZEB1, and KLF4 in hepatocellular carcinoma and their clinical significance

Background and objective: Metastasis-associated in colon cancer-1 (MACC1) is involved in the progression and metastasis of various cancers. Zinc finger E-box-binding homeobox 1 (ZEB1) is a key transcriptional factor of the epithelial-mesenchymal transition (EMT) that is involved in the migration and invasion of cancer cells. Kruppel-like factor 4 (KLF4) is a tumor suppressor that can inhibit tumor cell proliferation, migration, and metastasis. The purpose of this study was to investigate the expressions and clinical significance of MACC1, ZEB1, and KLF4 in hepatocellular carcinoma (HCC). Methods: We analyzed the expressions of MACC1, ZEB1, and KLF4 in 153 HCC specimens and their corresponding control specimens. The patients' clinicopathological and follow-up data were also collected. Results: The rates of positive expression of MACC1 and ZEB1 were significantly higher in the HCC specimens than in the control specimens, and their expressions were positively associated with the number of tumors, grades of differentiation, lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stages. Inversely, the rate of positive expression of KLF4 was significantly lower in the HCC specimens than it was in the control specimens, and its expression was negatively correlated with the number of tumors, grades of differentiation, LNM, and TNM stages. The patients who expressed MACC1 or ZEB1 had a reduced overall survival (OS) when compared with patients not expressing these proteins. However, the patients who expressed KLF4 had an increased OS when compared with patients who did not show any KLF4 expression. A multivariate analysis indicated that the expressions of MACC1, ZEB1, and KLF4 and tumor size, LNM, as well as the TNM stages were independent, prognostic factors for HCC patients. Conclusions: Therefore, positive expressions of MACC1, ZEB1, and KLF4 should be correlated with the duration of OS in patients with HCC and considered promising prognostic biomarkers, as well as potential therapeutic targets for HCC.