Repurposing DPP-4 Inhibitors for Colorectal Cancer: A Retrospective and Single Center Study

Abstract

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.

CD26 Induces Colorectal Cancer Angiogenesis and Metastasis through CAV1/MMP1 Signaling

“…Actually, CD26 inhibitor, also known as DPP4 inhibitor or gliptin, are a class of oral hypoglycemic drugs that antagonize the enzyme DPP4 and are approved to treat diabetes mellitus type 2 (DM-II). We and others recently reported that CRC patients with concurrent DM-II demonstrated better prognosis when treated with CD26 inhibitors [20][21][22]. Further research on CD26 and its inhibitors is warranted to provide further support for targeting CD26 in CRC treatment.…”

High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients

“…The immune system plays the most vital role in protection against diseases, including cancer. We previously reported that certain immune cell levels are correlated with the prognosis of post-operative CRC patients [ 24 ]. Hence, in this study, we investigated the association between tumor and NAT CBX8 level with immune cell profile of pre-operative and post-operative blood samples, as well as the dynamic changes in their level between post- and pre-operative blood (expressed as a delta value, which is calculated as post-operative level minus pre-operative level).…”

A Study on Methodologies of Drug Repositioning Using Biomedical Big Data: A Focus on Diabetes Mellitus

“…An alpha 1-adrenoceptor antagonist, known to treat benign prostate hyperplasia, was reportedly beneficial for blood sugar control [ 35 ]. Furthermore, dipeptidyl peptidase-4 inhibitor (DPP4i) showed promising results in the prognosis of colorectal cancer [ 36 ].…”

“…Despite particular cases that benefited from the use of chloroquine, it is difficult to be confident regarding the efficacy of a drug before similar effects are observed in large-scale studies [ 38 , 39 ]. Taking DM as an example, it appears that various antihyperglycemic therapies have other than hypoglycemic effects ( Table 2 ) [ 10 - 12 , 26 , 36 , 40 - 51 ]. In addition, other types of drugs are likely to help lower blood sugar levels in diabetic patients ( Table 3 ) [ 13 , 24 , 25 , 30 , 32 , 35 , 52 ].…”