XAF1 as a prognostic biomarker and therapeutic target in pancreatic cancer
Authors: Hua-feng Wang
Yong-ping Zhang
Qi Zhu
Jia Huang
Yao-zong Yuan
Wei-yan Yao
Fei Yuan
Shui-ping Tu
Journal: Cancer science (2010)
Discipline: CLINICAL MEDICINE
Keywords: XAF1; XIAP; apoptosis; pancreatic carcinogenesis; prognostic values
Affiliations: Department of Gastroenterology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract:  XAF1 (X chromosome-linked inhibitor of apoptosis [XIAP]-associated factor 1) is a novel XIAP modulator that negatively regulates the anti-apoptotic effects of XIAP and sensitizes cells to other cell death triggers. It has been reported to be downregulated in a variety of human cancer cell lines. However, the role of XAF1 in pancreatic carcinogenesis remains unclear. In the present study, we investigated the prognostic values of XAF1 expression and its regulation in cancer cell growth and apoptosis both in vitro and in vivo. From the immunohistochemistry staining of tissue microarray, 40 of 89 (44.9%) pancreatic specimens showed low levels of XAF1 expression. Statistical analysis suggested the downregulation of XAF1 was significantly correlated with tumor staging (P = 0.047) and those patients with low XAF1 levels had shorter survival times (P = 0.0162). Multivariate analysis indicated that XAF1 expression was an independent prognostic indicator of the survival of patients with pancreatic cancer (P = 0.007). Furthermore, we found that restoration of XAF1 expression mediated by Ad5/F35 virus suppressed cell proliferation and induced cell cycle arrest and apoptosis, accompanied by the activation of caspases 3, 8, and 9 and poly(ADP-ribose) polymerase as well as increased level of cytochrome c and Bid cleavage. Notably, XAF1 restoration robustly decreased survivin expression rather than XIAP. In addition, in vivo s.c. xenografts from Ad5/F35-XAF1 treatment, which showed less cellular proliferation and enhanced apoptosis, were significantly smaller than those from control groups. Our findings document that XAF1 is a valuable prognostic marker in pancreatic cancer and could be a potential candidate for cancer gene therapy. 

Retracted: No

PubPeer comments:
 ![file] , 
 Thank you for your interest in our work. After receiving your inquiries, I immediately re-examined our raw data with the team, and found some problems in Figure 3A as you pointed out. In Figure 3A, we confused the u00df-actin lines in those two groups (BxPC-3 and SW1990) because of our negligenceuff0cnow the original u00df-actin lines 1-6 are shown in original figure and we have corrected these mistakes as shown in revised Figure. I feel really sorry for any inconvenience it might have caused and I sincerely hope to revise our mistakes in order to keep the validity of our scientific work. ![file] , 
 Thank you for your interest in our work. After receiving your inquiries, I immediately re-examined our raw data with the team, and found some problems in Figure 3A as you pointed out. In Figure 3A, we confused the u00df-actin lines in those two groups (BxPC-3 and SW1990) because of our negligenceuff0cnow the original u00df-actin lines 1-6 are shown in original figure and we have corrected these mistakes as shown in revised Figure. I feel really sorry for any inconvenience it might have caused and I sincerely hope to revise our mistakes in order to keep the validity of our scientific work. ![file] , 
 #1 #1 Thank you for your interest in our work. After receiving your inquiries, I immediately re-examined our raw data with the team, and found some problems in Figure 3A as you pointed out. In Figure 3A, we confused the u00df-actin lines in those two groups (BxPC-3 and SW1990) because of our negligenceuff0cnow the original u00df-actin lines 1-6 are shown in original figure and we have corrected these mistakes as shown in revised Figure. I feel really sorry for any inconvenience it might have caused and I sincerely hope to revise our mistakes in order to keep the validity of our scientific work. ![file] ,