Potential of soluble CD26 as a serum marker for colorectal cancer detection

Cordero, Oscar J.; Imbernón, Mónica; Chiara, Loretta De; Martínez-Zorzano, Vicenta S.; Ayude, Daniel; Cadena, Marı́a Páez de la; Rodrı́guez-Berrocal, Francisco Javier

doi:10.5306/wjco.v2.i6.245

Cited by 39 publications

(45 citation statements)

References 227 publications

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“…Another protein candidate herein was DPP4, also known as CD26, a widely distributed 110 kDa transmembrane glycoprotein with peptidase activity. DPP4 is expressed as a cell surface antigen in melanocytes, epithelial cells, and lymphocytes (55)(56)(57), is a functional receptor for collagen, and is essential for normal immune function (58). Moreover, there are significant levels of DPP4 activity in plasma, serum (sCD26), and urine (59).…”

Section: Discussionmentioning

confidence: 99%

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Liu

Chen

Wang³

et al. 2015

Molecular & Cellular Proteomics

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Pleural effusion (PE), a tumor-proximal body fluid, may be a promising source for biomarker discovery in human cancers. Because a variety of pathological conditions can lead to PE, characterization of the relative PE proteomic profiles from different types of PEs would accelerate discovery of potential PE biomarkers specifically used to diagnose pulmonary disorders. Using quantitative proteomic approaches, we identified 772 nonredundant proteins from six types of exudative PEs, including three malignant PEs (MPE, from lung, breast, and gastric cancers), one lung cancer paramalignant PE, and two benign diseases (tuberculosis and pneumonia). Spectral counting was utilized to semiquantify PE protein levels. Principal component analysis, hierarchical clustering, and Gene Ontology of cellular process analyses revealed differential levels and functional profiling of proteins in each type of PE. We identified 30 candidate proteins with twofold higher levels (q<0.05) in lung cancer MPEs than in the two benign PEs. Three potential markers, MET, DPP4, and PTPRF, were further verified by ELISA using 345 PE samples. The protein levels of these potential biomarkers were significantly higher in lung cancer MPE than in benign diseases or lung cancer paramalignant PE. The area under the receiver-operator characteristic curve for three combined biomarkers in discriminating lung cancer MPE from benign diseases was 0.903. We also observed that the PE protein levels were more clearly discriminated in effusions in which the cytological examination was positive and that they would be useful in rescuing the false negative of cytological examination in diagnosis of nonsmall cell lung cancer-MPE. Western blotting analysis further demonstrated that MET overexpression in lung cancer cells would contribute to the elevation of soluble MET in MPE. Our results collectively demonstrate the utility of label-free quantitative proteomic approaches in establishing differential PE proteomes and provide a new database of proteins that can be used to facilitate identification of pulmonary disorder-related biomarkers. Molecular & Cellular Proteomics

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Section: Discussionmentioning

confidence: 99%

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Liu

Chen

Wang³

et al. 2015

Molecular & Cellular Proteomics

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“…We found a lack of any association of sCD26 levels with tumor localization, size, type, differentiation, TNM, stage or lymph node metastases. Accordingly Cordero and colleagues [12,13] did not found any relationship between the levels of sCD26 and the Dukes' stage classification in patients affected by colorectal cancer. These data collectively suggest the potential usefulness of this molecule for early diagnosis of gastric cancer.…”

Section: Discussionmentioning

confidence: 92%

“…Also serum CD26 is substantially dysregulated in various cancers: serum CD26 levels are increased in patients with hepatic cancer and decreased in patients with blood, thyroid and oral cancers [10,11]. Recently, CD26 has been identified as a serum marker for colorectal cancer detection and prognostic factor [12][13][14] while to best of our knowledge no study investigated the role of serum CD26 in presence of gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, serum DPP4 levels is increased in patients with hepatic cancer and decreased in patients with blood, solid and oral cancer [10,11]. Recently, CD26 has been identified as a serum marker for colorectal cancer detection [11][12][13] as well as a prognostic factor able to promote human colorectal cancer metastasis [14], while to best of our knowledge no study investigated the role of serum CD26 in gastric cancer. Only a previous study suggested that CD26 expression level in surgical samples may be considered a reliable biomarker of malignant GISTs of the stomach characterized by distinct clinical, genetic, and histopathological features [15].…”

Section: Introductionmentioning

confidence: 99%

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Serum CD26 levels in patients with gastric cancer: A novel potential diagnostic marker

Marano

Listorti

Luca

et al. 2018

European Journal of Surgical Oncology

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Background: CD26 is an ectoenzyme with dipeptidyl peptidase 4 (DPP4) activity expressed on a variety of cell types. Considering that serum CD26 levels have been previously associated with different cancers, we examined the potential diagnostic value of serum CD26 levels in gastric cancer. Methods: Soluble serum CD26 levels were measured in pre and postoperative serum samples of 30 patients with gastric cancer and in 24 healthy donors by a specific ELISA kit. Results: We found significantly lower serum CD26 levels in patients with gastric cancer (557.7 ± 118.3 pg/mL) compared with healthy donors (703.4 ± 170.3 pg/mL). Moreover patients with HER2 positive tumors had significantly lower CD26 serum levels (511.8 ± 84.8 pg/mL) compared with HER2 negative tumors (619.1 ± 109.9 pg/mL, p = 0.006). A binary logistic model having gastric cancer as the dependent variable while age, gender, CEA, CA19.9 and CD26 levels as covariates, showed that CD26 serum levels were independently associated with gastric cancer presence. Indeed after 3 months from surgery serum CD26 levels significantly increased (700.1 ± 119.9 pg/mL vs 557.7 ± 118.3 pg/ml) in all patients (t = −4.454, p < 0.0001). Conclusions: This is a preliminary study showing that the measurement of serum CD26 levels could represent an early detection marker for gastric cancer.

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“…DPP-IV and FAP are type II-transmembrane proteins that are enzymatically active as homodimers with a molecular weight (MW) typically of 220-240 kDa and 170 kDa, respectively 14,15 . Enzymatically active soluble forms of both enzymes lacking the transmembrane region are found in blood plasma, and in the case of DPP-IV also in other bodily fluids, but their origin is largely speculative 16,17 . In addition to these forms which are probably the result of shedding from the plasma membrane by an unknown protease, substantial molecular heterogeneity has been reported for both DPP-IV and FAP from various sources, and these molecular forms are thought to have unique pathophysiological functions.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas

Matrasova

Bušek

Balážiová

et al. 2017

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background and Aims. Proteolytic enzymes contribute to the progression of various cancers. We previously reported increased expression of the proline specific peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast activation protein (FAP) in human glioblastomas. Here we analyze the molecular heterogeneity of DPP-IV and FAP in glioblastomas. Methods. ELISA, isoelectric focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were utilized to analyze DPP-IV and FAP isoforms. Cell fractionation using a Percoll gradient and deglycosylation with PNGase F were performed to analyze the possible basis of DPP-IV and FAP microheterogeneity. Results. Molecular forms of DPP-IV with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were detected in human glioblastoma; in some tumors additional isoforms with a more acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. Using 2D electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5) pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. In glioma cell lines in vitro, several isoforms of both enzymes were expressed, however the alkalic forms present in glioblastoma tissues were not detected. Removal of N-linked oligosaccharides decreased the estimated molecular weight of both enzymes; the overall pattern of molecular forms nevertheless remained unchanged. Conclusion. Several isoforms of DPP-IV and FAP are present in glioblastoma tissue. The absence of alkaline isoforms of both enzymes in glioma cell lines however suggests that isoforms from other, most likely stromal, cell types contribute to the overall pattern seen in glioblastoma tissues.

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Potential of soluble CD26 as a serum marker for colorectal cancer detection

Cited by 39 publications

References 227 publications

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Serum CD26 levels in patients with gastric cancer: A novel potential diagnostic marker

Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas

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