The expression level of gene MAP4K4 and its clinical effect in cancerous tissue of gastric carcinoma
BIOMEDICAL RESEARCH-INDIA
Authors: Huo, Jian; Qiao, Jing-gui; Han, Kun
Abstract
Objective: To clarify the expression of MAP4K4 in gastric carcinoma and its relationship with clinical pathological features of gastric carcinoma and further reveal the role of MAP4K4 in the development of gastric cancer. Methods: We randomly selected 20 patients diagnosed with GC by clinical signs and symptoms, imaging diagnosis and laboratory diagnosis in department of general surgery in University Medical department Affiliated Hospital from January 2014 to December 2015. Gastric cancer tissues and adjacent tissues were studied with immuno histochemistry staining and the expression level of MAP4K4 level was detected postoperatively. The relationship between the MAP4K4 expression level and the clinical stage, pathological grade relationship was analysed. The Kaplan-Meier method was used to analyse the effect of MAP4K4 expression level on clinical outcome. Result: The expression level of MAP4K4 gene was related to lymph node metastasis and pathological staging of gastric cancer (P<0.05), but it was not related to the tumor size and recurrence and metastasis of gastric cancer (P>0.05). In the -similar to+ group, the median progression free survival was (4.98 +/- 14.42) months; the median progression of free survival was (34.00 +/- 27.56) months. In ++similar to+++ group, the median progression free survival was (19.57 +/- 4.76) months, and the median progression free survival was (13.00 +/- 1.25) months. The difference was statistically significant (2=13.167; P=0.005). In-similar to+ group, the average survival time was (65 +/- 116.70) months, the median overall survival was (50 +/- 39.90) months. The difference was statistically significant (2=10.084; P=0.003). Conclusion: The expression level of MAP4K4 in gastric cancer patients was significantly increased, and it was negatively correlated with the pathological grade of gastric cancer.
ShRNA-Targeted MAP4K4 Inhibits Hepatocellular Carcinoma Growth
CLINICAL CANCER RESEARCH
Authors: Liu, An-Wen; Cai, Jing; Zhao, Xiang-Li; Jiang, Ting-Hui; He, Tian-Feng; Fu, Hua-Qun; Zhu, Ming-Hua; Zhang, Shu-Hui
Abstract
Purpose: Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is overexpressed in many types of cancer. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in hepatocellular carcinoma (HCC). Experimental Design: MAP4K4 expression was examined in 20 fresh HCCs and corresponding nontumor liver tissues. Immunohistochemistry for MAP4K4 was performed on additional 400 HCCs, of which 305 (76%) were positive for hepatitis B surface antigens. The clinical significance of MAP4K4 expression was analyzed. MAP4K4 downregulation was performed in HCC cell lines HepG2 and Hep3B with high abundance of MAP4K4, and the effects of MAP4K4 silencing on cell proliferation in vitro and tumor growth in vivo were evaluated. Quantitative real-time PCR arrays were employed to identify the MAP4K4-regulated signaling pathways. Results: MAP4K4 was aberrantly overexpressed in HCCs relative to adjacent nontumor liver tissues. This overexpression was significantly associated with larger tumor size, increased histologic grade, advanced tumor stage, and intrahepatic metastasis, as well as worse overall survival and higher early recurrence rate. Knockdown of the MAP4K4 expression reduced cell proliferation, blocked cell cycle at S phase, and increased apoptosis. The antitumor effects of MAP4K4 silencing were also observed in vivo, manifested as retarded tumor xenograft growth. Furthermore, multiple tumor progression-related signaling pathways including JNK, NF kappa B, and toll-like receptors were repressed by MAP4K4 downregulation. Conclusions: MAP4K4 overexpression is an independent predictor of poor prognosis of HCC patients, and inhibition of its expression might be of therapeutic significance. Clin Cancer Res; 17(4); 710-20. (C) 2010 AACR.