Dejun Yang1, Yu Zhang1, Yajun Cheng1, Liang Hong2, Changming Wang1, Ziran Wei1, Qingping Cai3, Ronglin Yan4. 1. Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China. 2. Outpatient Department, Yichuan Community Health Service Center, 43 Lishan Road, Shanghai, 200065, People's Republic of China. 3. Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China. caiqp1969@hotmail.com. 4. Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China. yanronglin@smmu.edu.cn.
Abstract
BACKGROUND: Cell division cycle 42 (CDC42), an important member of the Rho family, is overexpressed in various human cancers. However, its expression and role in pancreatic cancer (PC) are not well understood. AIM: The present study was designed to investigate the expression patterns and underlying cellular mechanisms of CDC42 in PC. METHODS: First, immunohistochemical analysis, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect CDC42 expression in clinical pancreatic carcinoma and adjacent tissues. Second, differential expression of CDC42 between PC cells and normal cells was evaluated by qRT-PCR and Western blotting. Third, the correlation between CDC42 expression as well as clinicopathological characteristics and patient survival was analyzed. Finally, CDC42 was knocked down to examine its role both in vivo and in vitro. RESULTS: The results showed significantly increased CDC42 expression in pancreatic tumor tissues compared with adjacent normal tissues, as revealed by qRT-PCR, Western blotting and immunostaining. Compared to PanC-1 cells, CDC42 expression was downregulated in HPDE6-C7 cells as shown by qRT-PCR and Western blotting. High CDC42 expression was observed in 69.2% (83/120) of pancreatic adenocarcinoma patients and was significantly associated with tumor differentiation (p = 0.013), median tumor size (p = 0.005), tumor infiltration (pT stage, p = 0.04), lymph nodal status (pN stage, p = 0.044) and TNM staging (p = 0.003). Multivariate Cox regression analysis revealed CDC42 expression to be an independent predictor of survival of PC patients (HR 3.0, 95% CI 1.60-5.61, p = 0.001). Finally, we found that CDC42 promoted the proliferation of PanC-1 cells both in vivo and in vitro. CONCLUSIONS: Our findings reveal that CDC42 might play an important role in promoting PC development, and the findings suggest that CDC42 might serve as a potential prognostic indicator of PC.
BACKGROUND: Cell division cycle 42 (CDC42), an important member of the Rho family, is overexpressed in various humancancers. However, its expression and role in pancreatic cancer (PC) are not well understood. AIM: The present study was designed to investigate the expression patterns and underlying cellular mechanisms of CDC42 in PC. METHODS: First, immunohistochemical analysis, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect CDC42 expression in clinical pancreatic carcinoma and adjacent tissues. Second, differential expression of CDC42 between PC cells and normal cells was evaluated by qRT-PCR and Western blotting. Third, the correlation between CDC42 expression as well as clinicopathological characteristics and patient survival was analyzed. Finally, CDC42 was knocked down to examine its role both in vivo and in vitro. RESULTS: The results showed significantly increased CDC42 expression in pancreatic tumor tissues compared with adjacent normal tissues, as revealed by qRT-PCR, Western blotting and immunostaining. Compared to PanC-1 cells, CDC42 expression was downregulated in HPDE6-C7 cells as shown by qRT-PCR and Western blotting. High CDC42 expression was observed in 69.2% (83/120) of pancreatic adenocarcinomapatients and was significantly associated with tumor differentiation (p = 0.013), median tumor size (p = 0.005), tumor infiltration (pT stage, p = 0.04), lymph nodal status (pN stage, p = 0.044) and TNM staging (p = 0.003). Multivariate Cox regression analysis revealed CDC42 expression to be an independent predictor of survival of PC patients (HR 3.0, 95% CI 1.60-5.61, p = 0.001). Finally, we found that CDC42 promoted the proliferation of PanC-1 cells both in vivo and in vitro. CONCLUSIONS: Our findings reveal that CDC42 might play an important role in promoting PC development, and the findings suggest that CDC42 might serve as a potential prognostic indicator of PC.
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