High Expression of Cell Division Cycle 42 Promotes Pancreatic Cancer Growth and Predicts Poor Outcome of Pancreatic Cancer Patients.
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.



The present study was designed to investigate the expression patterns and underlying cellular mechanisms of CDC42 in PC.



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.



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.



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.
Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China.
Dejun
D
Yang
Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China.
Yu
Y
Zhang
Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China.
Yajun
Y
Cheng
Outpatient Department, Yichuan Community Health Service Center, 43 Lishan Road, Shanghai, 200065, People's Republic of China.
Liang
L
Hong
Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China.
Changming
C
Wang
Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China.
Ziran
Z
Wei
Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China. caiqp1969@hotmail.com.
Qingping
Q
Cai
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.
Ronglin
R
Yan
D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011897:Random Allocation; D016896:Treatment Outcome; D020764:cdc42 GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D020764:cdc42 GTP-Binding Protein
Biomarker; Cell division cycle 42; Immunohistochemistry; Pancreatic cancer; Prognosis