Type

Other / n/a

Authors

Jochen HM Prehn
Deborah A McNamara
Joseph Deasy
Elaine W Kay
Andreas U Lindner
Orna Bacon
J Fay
Joan Kehoe
Lorna Flanagan

Subjects

Biochemistry

Topics
apoptosis physiology physics rectal cancer neoadjuvant radio chemotherapy x linked inhibitor inhibitor of apoptosis proteins x linked inhibitor of apoptosis protein

High levels of X-linked Inhibitor-of-Apoptosis Protein (XIAP) are indicative of radio chemotherapy resistance in rectal cancer. (2015)

Abstract BACKGROUND: The mainstay of treatment in rectal cancer is neoadjuvant radio chemotherapy prior to surgery, in an attempt to downstage the tumour, allowing for more complete removal during surgery. In 40 % of cases however, this neoadjuvant radio chemotherapy fails to achieve tumour regression, partly due insufficient apoptosis signaling. X-linked Inhibitor of Apoptosis Protein (XIAP) is an anti-apoptotic protein that has been reported to contribute to disease progression and chemotherapy resistance.METHODS: We obtained rectal biopsy normal and matched tumour tissue from 29 rectal cancer patients with varying degrees of tumour regression, and using Western blot, examined anti-apoptotic XIAP and pro-apoptotic Smac protein levels in these tissues, with the aim to examine whether disturbed XIAP/Smac levels may be an indicator of neoadjuvant radio chemotherapy resistance. Expression of inhibitor of apoptosis proteins cIAP-1 and cIAP-2 was also examined.RESULTS: We found that levels of XIAP increased in accordance with the degree of radio chemotherapy resistance of the tissue. Levels of this protein were also significantly higher in tumour tissue, compared to matched normal tissue in highly resistant tissue. In contrast, Smac protein levels did not increase with radio chemotherapy resistance, and the protein was similarly expressed in normal and tumour tissue, indicating a shift in the balance of these proteins. Post treatment surgical resection tissue was available for 8 patients. When we compared matched tissue pre- and post- radio chemotherapy we found that XIAP levels increased significantly during treatment in both normal and tumour tissue, while Smac levels did not change. cIAP-1 and cIAP-2 levels were not differentially expressed in varying degrees of radio chemotherapy resistance, and neoadjuvant therapy did not alter expression of these proteins.CONCLUSION: These data indicate that disturbance of the XIAP/Smac balance may be a driver of radio chemotherapy resistance, and hence high levels of XIAP may be a useful indicator of neoadjuvant radio chemotherapy resistance in rectal cancer. Moreover, as XIAP levels increase with radio chemotherapy it is possible that a subset of more resistant tumour cells survive this treatment and may be resistant to further adjuvant treatment. Patients with resistant tumours highly expressing XIAP may benefit from alternative treatment strategies, such as Smac mimetics post neoadjuvant radio chemotherapy.
Collections Ireland -> Royal College of Surgeons in Ireland -> Physiology and Medical Physics Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Physiology and Medical Physics

Full list of authors on original publication

Jochen HM Prehn, Deborah A McNamara, Joseph Deasy, Elaine W Kay, Andreas U Lindner, Orna Bacon, J Fay, Joan Kehoe, Lorna Flanagan

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Deborah A McNamara
Royal College of Surgeons in Ireland
Total Publications: 17
 
3
Elaine W Kay
Royal College of Surgeons in Ireland
Total Publications: 157
 
4
Andreas U Lindner
Royal College of Surgeons in Ireland
Total Publications: 13
 
5
Orna Bacon
Royal College of Surgeons in Ireland
Total Publications: 13
 
6
Joanna Fay
Royal College of Surgeons in Ireland
Total Publications: 24
 
7
Lorna Flanagan
Royal College of Surgeons in Ireland
Total Publications: 23