Serum dipeptidyl peptidase IV activity and sCD26 concentration in patients with choroidal nevus or uveal melanoma

Varela-Calviño, Rubén; Imbernón, Mónica; Vázquez-Iglesias, Lorena; Cadena, Marı́a Páez de la; Bande-Rodríguez, Manuel; Piñeiro, Antonio; Pardo, María; Cordero, Oscar J.

doi:10.1016/j.cca.2015.07.007

Cited by 4 publications

(9 citation statements)

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“…The first important result in this study was that men showed statistically higher serum DPP4 activity than women, confirming the trend suggested in an early study [18]. This difference between sexes was not seen with the concentration of the serum protein (sCD26), in coherence with what others and we have reported several times [10][11][12]19]. On the other hand, DPP4 activity and sCD26 correlated in females but not in males, so there is obviously an unknown factor affecting this protein related to sex.…”

Section: Discussionsupporting

confidence: 92%

“…Measurement of DPP4 Enzyme Activity and Soluble CD26 Protein. DPP4 enzymatic activity was measured in 96-well culture plates using the substrate Gly-Pro-p-nitroanilide (0.2 mM; Sigma-Aldrich, USA), as described previously [10,12]. The sCD26 concentration was measured in duplicate with the Human DPP4/CD26 DuoSet ELISA kit (R&D Systems, USA) according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we have explored DPP4 enzymatic activity and sCD26 in serum from rheumatoid arthritis and uveal melanoma patients and in pleural effusions of benign and malignant lung diseases [10][11][12], finding complex degrees of correlation including differences between sexes. Several possible arguments could explain the complex relationship between both measures.…”

Section: Introductionmentioning

confidence: 99%

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CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context

et al. 2020

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Current screening trials are showing reduction in colorectal cancer incidence and mortality. However, participation rates are often low, and blood-based tests could complement existing screening strategies. CD26 protein (sCD26) and its dipeptidyl peptidase IV (DPP4) enzymatic activity in circulation have been proposed as biomarkers for colorectal cancer and other diseases. However, changes in sCD26 and DPP4 levels show complex degrees of correlation, and their physiological or pathophysiological role is unclear. The aim of this study was to analyse if anti-CD26 autoantibodies are related to sCD26 and DPP4 and to determine their relevance in a context of colorectal cancer screening for complementing the value of sCD26 and DPP4 as biomarkers. These biomarkers were measured in a large prospective cohort (n=497, except the anti-CD26 antibodies, evaluated in 125 samples) that included a subgroup of individuals that were positive for the faecal immunological occult blood test (FIT) (n=86) and underwent a colonoscopy (n=47). We confirmed for the first time higher DPP4 activity in men compared to women (Student’s t test, p=0.002), though this difference between sexes was not seen for serum sCD26 protein. These biomarkers correlated (R=0.246, p=0.003) only in women. Correlations were found between anti-CD26 isotypes but not with DPP4 activity or sCD26 concentration, except for a negative correlation only in men between anti-CD26 IgA isotype and sCD26 (R=−0.232, p=0.044), and an almost significant negative correlation between anti-CD26 IgG and sCD26 limited to FIT-positive men. Interestingly, patients with advanced adenomas displayed the most elevated mean levels of anti-CD26 IgA, IgM, and particularly IgG (Mann-Whitney U test, p=0.030) in comparison with the other FIT positives without adenomas, and these levels did not correlate with sCD26 or its DPP4 activity. Our preliminary results suggest that the combination of these measures using sex as confounder could perhaps be used as biomarkers for colorectal disease. It also suggests that events affecting the gut influence the levels of anti-CD26 antibodies, which show little or no effect in antigen clearance. These findings should be confirmed in a larger cohort of individuals with colonoscopy. The physiological origin of the sex differences observed should be further addressed.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context

et al. 2020

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“…No conclusions were drawn about the possible use of the observed differences in the diagnosis or follow-up of melanoma (Matić et al, 2012). In uveal malignant melanoma an increase in DPP4-activity has been reported, however this was a pilot study with a limited sample size and follow-up studies are needed to fully determine CD26/DPP4's potential as a marker for diagnosis or prognosis (Varela-Calviño et al, 2015).…”

Section: Skin and Eye Cancermentioning

confidence: 97%

CD26/DPP4 - a potential biomarker and target for cancer therapy

Enz

Vliegen

Meester

et al. 2019

Pharmacology & Therapeutics

123

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CD26/dipeptidyl peptidase (DPP)4 is a membrane-bound protein found in many cell types of the body, and a soluble form is present in body fluids. There is longstanding evidence that various primary tumors and also metastases express CD26/DPP4 to a variable extent. By cleaving dipeptides from peptides with a proline or alanine in the penultimate position at the N-terminus, it regulates the activity of incretin hormones, chemokines and many other peptides. Due to these effects and interactions with other molecules, a tumor promoting or suppressing role can be attributed to CD26/DPP4.In this review, we discuss the existing evidence on the expression of soluble or membrane-bound CD26/DPP4 in malignant diseases, along with the most recent findings on CD26/DPP4 as a therapeutic target in specific malignancies. The expression and possible involvement of the related DPP8 and DPP9 in cancer are also reviewed.A higher expression of CD26/DPP4 is found in a wide variety of tumor entities, however more research on CD26/DPP4 in the tumor microenvironment is needed to fully explore its use as a tumor biomarker. Circulating soluble CD26/DPP4 has also been studied as a cancer biomarker, however, the observed decrease in most cancer patients does not seem to be cancer specific. Encouraging results from experimental work and a recently reported first phase clinical trial targeting CD26/DPP4 in mesothelioma, renal and urological tumors pave the way for follow-up clinical studies, also in other tumor entities, possibly leading to the development of more effective complementary therapies against cancer.

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“…We hypothesize, at present, that some change in CD26+ immune subsets might be responsible for this sCD26 impairment [ 24 , 25 , 26 ]. Several studies in different cancers have found low correlations of sCD26 levels with its enzymatic activity dipeptidyl peptidase 4 (DPP4, EC 3.4.14.5) due to some referenced factors [ 27 , 28 , 29 , 30 ]. The aim of this study was to determine if sCD26 and its enzymatic activity can complement the performance of FIT for the early detection of CRC and AA, analyzing these biomarkers in cohorts of cancer and average-risk populations derived from the national screening program.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Blood Soluble CD26 as a Complementary Biomarker for Colorectal Cancer Screening Programs

Chiara

Barcia-Castro

Gallardo-Gómez

et al. 2022

Cancers

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Fecal hemoglobin immunodetection (FIT) in combination with endoscopy has been implemented to reduce mortality from colorectal cancer (CRC), although there are issues that can be improved in relation to participation rates. We studied whether the blood biomarker soluble-CD26 (sCD26), related at least in part to the immune system and inflammation, and/or its dipeptidyl peptidase enzyme activity (DPP4), could help reduce false positives. In a cohort of 1703 individuals who underwent colonoscopy and had a serum sample, sCD26 and DPP4 activity showed statistically significant differences regarding sex and age. According to the colonoscopy findings, sCD26 and DPP4 activity progressively decreased in advanced adenomas and CRC, with statistically significant differences, even between both groups; 918 of them had a FIT result (n = 596 positive cases) with approximately 70% of these (n = 412) false positives. With cut-offs of 440 ng/mL for sCD26, 42 mU/mL for DPP4, and 11 ng/mU for their ratio, the combined information of the three biomarkers (at least positive for one biomarker) identified almost all advanced adenomas and CRC cases in the FIT cohort with approximately half of the false positives compared to FIT. A sequential testing strategy with FIT and our blood biomarker test is proposed.

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Serum dipeptidyl peptidase IV activity and sCD26 concentration in patients with choroidal nevus or uveal melanoma

Cited by 4 publications

References 10 publications

CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context

CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context

CD26/DPP4 - a potential biomarker and target for cancer therapy

Evaluation of Blood Soluble CD26 as a Complementary Biomarker for Colorectal Cancer Screening Programs

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