A Multi-Center Retrospective Analysis Examining the Effect of Dipeptidyl Peptidase-4 Inhibitors on Progression-Free Survival in Patients With Prostate Cancer

Pan, Kelsey; Skelton, William Paul; Elzeneini, Mohammed; Nguyen, Thu-Cuc; Franke, Aaron J; Ali, Azka; Bishnoi, Rohit; Dang, Long H.; Dang, Nam H.; Kish, Julie A.

doi:10.7759/cureus.14712

Cited by 3 publications

(3 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has also been reported that abundant miR-92a-1-5p from PCa exosomes can downregulate COL1A1 and thus promote osteoclast differentiation and inhibit osteoblast genesis 18 . Pan et al 19 revealed the higher level of DPP4 in malignant prostate tissue than that in benign prostate tissue, its expression correlated with PSA and tumor stage. Kamata et al 20 reported that zinc finger mutation of PARP7 can result in the loss of PARP7, and further impact the enhancement of AR-dependent transcription of the MYBPC1 gene.…”

Section: Discussionmentioning

confidence: 99%

Risk subtyping and prognostic assessment of prostate cancer based on consensus genes

et al. 2022

View full text Add to dashboard Cite

Prostate cancer (PCa) is the most frequent malignancy in male urogenital system around worldwide. We performed molecular subtyping and prognostic assessment based on consensus genes in patients with PCa. Five cohorts containing 1,046 PCa patients with RNA expression profiles and recorded clinical follow-up information were included. Univariate, multivariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were used to select prognostic genes and establish the signature. Immunohistochemistry staining, cell proliferation, migration and invasion assays were used to assess the biological functions of key genes. Thirty-nine intersecting consensus prognostic genes from five independent cohorts were identified. Subsequently, an eleven-consensus-gene classifier was established. In addition, multivariate Cox regression analyses showed that the classifier served as an independent indicator of recurrence-free survival in three of the five cohorts. Combined receiver operating characteristic (ROC) analysis achieved synthesized effects by combining the classifier with clinicopathological features in four of five cohorts. SRD5A2 inhibits cell proliferation, while ITGA11 promotes cell migration and invasion, possibly through the PI3K/AKT signaling pathway. To conclude, we established and validated an eleven-consensus-gene classifier, which may add prognostic value to the currently available staging system.

show abstract

Section: Discussionmentioning

confidence: 99%

Risk subtyping and prognostic assessment of prostate cancer based on consensus genes

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Prior studies that investigated the link between DPP-4I exposure and PCa outcomes present a mixed picture. A multi-center retrospective analysis found that DPP-4I use compared to metformin use did not show a signi cant progression-free survival bene t in advanced-stage PCa [9]. However, it was limited by a small sample size of DPP-4I users (n = 41), while our study is better powered.…”

Section: Prior Studies and Future Directionsmentioning

confidence: 80%

Dipeptidyl peptidase-4 inhibitors and mortality risks in patients with prostate cancer receiving androgen deprivation therapy: a population-based cohort study

Hui¹,

Lee²,

Li³

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Dipeptidyl peptidase-4 inhibitors (DPP-4I) have demonstrated survival benefit in patients with cancer, but their impact on patients with prostate cancer (PCa), especially with androgen deprivation therapy (ADT), is unclear. This study examined the impact of DPP-4I use on mortality risks in patients with type 2 diabetes (T2D) and PCa receiving ADT. Methods Adults with T2D and PCa who received metformin and ADT attending public hospitals in Hong Kong between 1 January 2006 and 31 March 2021 were retrospectively identified. Patients with < 6 months of chemical castration without bilateral orchidectomy, < 6 months of concurrent DPP-4I and ADT use, or missing baseline HbA1c were excluded. DPP-4I users had ≥ 6 months of concurrent DPP-4I and ADT use, while non-users never had DPP-4I use. Included patients were followed-up until 30 September 2021. The endpoints were PCa-specific mortality and all-cause mortality. Inverse probability treatment weighting was used to balance covariates. Results In total, 1465 patients (286 DPP-4I users and 1179 non-users; mean age 76.0 ± 7.9 years old) were analyzed. Over a mean follow-up of 4.0 ± 3.0 years, DPP-4I users had lower risks of PCa-specific mortality (weighted hazard ratio (wHR) 0.40 [95% confidence interval (CI) 0.26–0.59], p < 0.001) and all-cause mortality (wHR 0.59 [95% CI 0.48–0.73], p < 0.001). Such associations were independent of diabetic control. Moreover, the association between DPP-4I use and risks of PCa-specific mortality was independent of chemotherapy or androgen receptor signaling inhibitor use. Conclusions DPP-4I use is associated with decreased mortality risks in patients with T2D and PCa receiving ADT.

show abstract

“…As mentioned, pharmacologic inhibitors of CD26/DPP4 have been in clinical use for over a decade to improve glucose tolerance in diabetic patients [ 66 ]. While distinct reports indicate an increase in incidence rates of selected cancers [ 110 , 111 , 112 ], other studies argue against an association of tumor incidence and CD26/DPP4 inhibition and some analyses even indicate that CD26/DPP4 inhibition might instead improve outcomes related to certain tumor types [ 113 , 114 , 115 , 116 , 117 , 118 ]. However, current clinical evidence is not sufficient to evaluate potential tumor-promoting or tumor-suppressive effects of CD26/DPP4 inhibition and functional explanations are still missing.…”

Section: Cd26/dpp4 In T-cell Malignanciesmentioning

confidence: 99%

The Serine Protease CD26/DPP4 in Non-Transformed and Malignant T Cells

Chitadze

Wehkamp

Janßen

et al. 2021

Cancers

View full text Add to dashboard Cite

CD26/Dipeptidylpeptidase 4 is a transmembrane serine protease that cleaves off N-terminal dipeptides. CD26/DPP4 is expressed on several immune cell types including T and NK cells, dendritic cells, and activated B cells. A catalytically active soluble form of CD26/DPP4 can be released from the plasma membrane. Given its wide array of substrates and interaction partners CD26/DPP4 has been implicated in numerous biological processes and effects can be dependent or independent of its enzymatic activity and are exerted by the transmembrane protein and/or the soluble form. CD26/DPP4 has been implicated in the modulation of T-cell activation and proliferation and CD26/DPP4-positive T cells are characterized by remarkable anti-tumor properties rendering them interesting candidates for T cell-based immunotherapies. Moreover, especially in cutaneous T-cell lymphoma CD26/DPP4 expression patterns emerged as an established marker for diagnosis and treatment monitoring. Surprisingly, besides a profound knowledge on substrates, interaction partners, and associated signal transduction pathways, the precise role of CD26/DPP4 for T cell-based immune responses is only partially understood.

show abstract

A Multi-Center Retrospective Analysis Examining the Effect of Dipeptidyl Peptidase-4 Inhibitors on Progression-Free Survival in Patients With Prostate Cancer

Cited by 3 publications

References 11 publications

Risk subtyping and prognostic assessment of prostate cancer based on consensus genes

Risk subtyping and prognostic assessment of prostate cancer based on consensus genes

Dipeptidyl peptidase-4 inhibitors and mortality risks in patients with prostate cancer receiving androgen deprivation therapy: a population-based cohort study

The Serine Protease CD26/DPP4 in Non-Transformed and Malignant T Cells

Contact Info

Product

Resources

About