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Repurposing DPP-4 Inhibitors for Colorectal Cancer: A Retrospective and Single Center Study
Lui Ng1, Dominic Chi-Chung Foo1, Carlos King-Ho Wong2
1Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Background:
There have been studies reporting the crucial roles of Dipeptidyl-peptidase 4 (DPP4) in colorectal cancer (CRC) initiation and progression, whereas DPP4-inhibitors are safe Food and Drug Association (FDA)-approved drugs for treating diabetes. This study aims to investigate the association between DPP4-inhibitor treatment and the prognosis of CRC patients.
Methods:
Clinical data of CRC patients with diabetes and the prescription of DPP4-inhibitors who had undergone curative surgery in our hospital between January 2006 and December 2015 were retrieved. Their survival data and immune cell population in circulatory blood were compared to those treated with metformin.
Results:
The DPP4-inhibitor patient group showed a significantly better 5-year disease-free survival (median DFS = 1733 days, 95% CI = 1596 to 1870 days) when compared to the metformin group (p = 0.030, median DFS = 1382 days, 95% CI = 1246 to 1518 days). 33 out of the 92 patients in the metformin group showed recurrence whereas only 3 of the 26 patients in the DPP4-inhibitor group showed recurrence (p = 0.033). Cox regression analysis demonstrated that DPP4-inhibitor application is a favorable factor associated with a lower risk of recurrence (Hazard ratio = 0.200, p = 0.035). Furthermore, our results suggested that the immune cell profile of CRC patients is a potential biomarker for response to DPP4-inhibitor treatment.
Conclusion:
This study demonstrated the association of DPP4-inhibitor treatment with a better prognosis of CRC patients.
Insights
Dipeptidyl-peptidase 4 (DPP4)-inhibitor treatment is associated with improved survival and reduced recurrence in colorectal cancer (CRC) patients. This suggests DPP4-inhibitors may offer a better prognosis for CRC patients with diabetes.
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Dipeptidyl-peptidase 4 (DPP4) plays a role in colorectal cancer (CRC) development.
- DPP4-inhibitors are FDA-approved diabetes drugs.
- The potential benefit of DPP4-inhibitors in CRC prognosis is unexplored.
Purpose of the Study:
- To investigate the association between DPP4-inhibitor treatment and colorectal cancer (CRC) patient prognosis.
- To compare outcomes of CRC patients treated with DPP4-inhibitors versus metformin.
Main Methods:
- Retrospective analysis of CRC patients with diabetes who underwent surgery.
- Comparison of survival data and immune cell profiles between DPP4-inhibitor and metformin groups.
- Cox regression analysis to identify prognostic factors.
Main Results:
- DPP4-inhibitor group showed significantly better 5-year disease-free survival than the metformin group (p=0.030).
- Lower recurrence rates observed in the DPP4-inhibitor group (3/26) compared to the metformin group (33/92) (p=0.033).
- DPP4-inhibitor use was a favorable prognostic factor, reducing recurrence risk (HR=0.200, p=0.035). Immune cell profiles may predict treatment response.
Conclusions:
- DPP4-inhibitor treatment is associated with improved prognosis in colorectal cancer (CRC) patients.
- DPP4-inhibitors represent a potential therapeutic strategy for improving CRC outcomes in diabetic patients.
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