Increased CDC20 expression is associated with development and progression of hepatocellular carcinoma

Abstract

Cell division cycle 20 (CDC20) encodes a regulatory protein interacting with the anaphase-promoting complex/cyclosome (APC/C) in the cell cycle and plays important roles in tumorigenesis and progression of multiple tumors. The present study aimed to investigate the clinical significance of CDC20 in hepatocellular carcinoma (HCC) and the role of CDC20 in the progression of HCC. By bioinformatics analysis, CDC20 was found to be the major node in HCC molecular interaction networks. Quantitative PCR and western blot analyses were applied to examine CDC20 expression in 16 paired primary HCC tissues. Immunohistochemistry (IHC) was performed to examine CDC20 protein expression in 132 matched paraffin-embedded HCC tissues and to analyze the relationship between CDC20 staining and clinical characteristics. Small interfering RNA (siRNA) targeting CDC20 was synthesized and transfected into HepG2 cells to investigate the role of CDC20 in cell growth and the cell cycle. Results show that CDC20 expression was upregulated in HCC tissues compared to adjacent non-tumor liver tissues. In the 132 matched HCC tissues, high expression levels of CDC20 were detected in 68.18% HCC samples, and overexpression of CDC20 was positively correlated with gender (P=0.013), tumor differentiation (P=0.000), TNM stage (P=0.012), P53 and Ki-67 expression (P=0.023 and P=0.007, respectively). Cells transfected with CDC20 siRNA showed a decrease in cell proliferation and increase in the number of cells in G2/M-phase. In conclusion, increased expression of CDC20 was demonstrated to be associated with the development and progression of HCC, and may be regarded as a promising therapeutic target for HCC.

A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage

“…Regarding correlation of CDC20 overexpression and tumor stage, we noted that CDC20 overexpression was significantly associated with advanced tumor stage in carcinomas of the breast, colon, endometrium, and prostate. Similar results were noted by some of the previous cohorts [25,26,39]. However, other previous studies reported that CDC20 overexpression was not correlated with tumor stage [23,24,27,[36][37][38].…”

“…This difference was reaching a statistically significant level in carcinomas of the bladder, cervix, colon, endometrium, kidney, liver, ovary, prostate, and stomach. In concordance with our study, previous studies were reported such results [23,25,26,[36][37][38][39][40]. However, the difference did not reach a statistically significant level as reported by [24,27].…”

“…CDC20 expression was detected in the nuclei and/or cytoplasm of the tumor cells as shown in previous studies [23,25,26,36,38,39]. CDC20 overexpression was detected in 55.7 % while low CDC20 expression was found in 44.3 % of all examined malignant tumors.…”

“…Positive CDC20 expression was observed in the breast, colon, endometrium, head and neck, kidney, lung, ovary, pancreas, prostate, and testis. Previous studies reported positive CDC20 expression in the normal/non-neoplastic epithelial cells of Graph 1 CDC20 immunohistochemical expression in normal/non-neoplastic tissues and primary malignant tumors from multiple organs the colon, stomach, head and neck, and pancreas (23,26,27,36), while others reported that CDC20 expression was negative in normal/non-neoplastic epithelial cells of the bladder, breast, cervix, liver, and lung [24,25,[37][38][39]. Our comprehensive study corroborated and expanded these observations as we found negative CDC20 expression in normal/non-neoplastic tissues from the bladder, cervix, liver, stomach, and thyroid.…”

“…Li et al [39] reported that CDC20 expression was upregulated in HCC tissues compared to the adjacent non-tumor liver tissues and these high expression levels of CDC20 were detected in 68.18 % HCC samples. Regarding lung carcinoma, positive CDC20 expression was present in 46.7 % of all cases.…”