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1.  Potential of soluble CD26 as a serum marker for colorectal cancer detection 
Colorectal cancer is characterized by a low survival rate even though the basis for colon cancer development, which involves the evolution of adenomas to carcinoma, is known. Moreover, the mortality rates continue to rise in economically transitioning countries although there is the opportunity to intervene in the natural history of the adenoma–cancer sequence through risk factors, screening, and treatment. Screening in particular accounted for most of the decline in colorectal cancer mortality achieved in the USA during the period 1975-2000. Patients show a better prognosis when the neoplasm is diagnosed early. Among the variety of screening strategies, the methods range from invasive and costly procedures such as colonoscopy to more low-cost and non-invasive tests such as the fecal occult blood test (guaiac and immunochemical). As a non-invasive biological serum marker would be of great benefit because of the performance of the test, several biomarkers, including cytologic assays, DNA and mRNA, and soluble proteins, have been studied. We found that the soluble CD26 (sCD26) concentration is diminished in serum of colorectal cancer patients compared to healthy donors, suggesting the potential utility of a sCD26 immunochemical detection test for early diagnosis. sCD26 originates from plasma membrane CD26 lacking its transmembrane and cytoplasmic domains. Some 90%–95% of sCD26 has been associated with serum dipeptidyl peptidase IV (DPP-IV) activity. DPP-IV, assigned to the CD26 cluster, is a pleiotropic enzyme expressed mainly on epithelial cells and lymphocytes. Our studies intended to validate this test for population screening to detect colorectal cancer and advanced adenomas are reviewed here.
PMCID: PMC3139035  PMID: 21773075
Antibody arrays; Bioinformatics; Biomarkers; cancer; Clustering; Cytometric beads; Diagnosis; Dipeptidyl peptidase IV; Enzyme linked immunosorbent assay; Prognosis; Review; Soluble CD26; Screening; Serum
2.  Postoperative Serum Levels of sCD26 for Surveillance in Colorectal Cancer Patients 
PLoS ONE  2014;9(9):e107470.
One of the main aims of the follow-up after curative resection of colorectal cancer is the early detection and treatment of tumor recurrence. We previously demonstrated decreased preoperative soluble CD26 (sCD26) levels in serum from colorectal cancer patients. We extended now the study to investigate if sCD26 levels in postoperative serum serve as marker of recurrence of the disease during surveillance. Soluble sCD26 was measured in pre- and postoperative serum samples of 43 patients with primary colorectal cancer. Carcinoembryonic antigen, carbohydrate antigen 19.9 and 72.4 levels were also measured during surveillance. The average follow-up period was 41.8±20.8 months. sCD26 levels during follow-up showed well-defined patterns in patients without disease (n = 28), and in patients with tumor persistence (n = 2), local recurrence (n = 3) or distant metastasis (n = 10). Disease-free patients showed stable levels between 460–850 ng/mL during follow-up, while high (over 850 ng/mL) and unstable sCD26 levels were found before recurrence was diagnosed. The mean maximum/minimum sCD26 ratios during surveillance were 1.52, 2.12 and 2.63 for patients with no recurrence, local recurrence and metastasis, respectively (p = 0.005). From the cut-off obtained from a receiver operator characteristics (ROC) curve built with the maximum/minimum sCD26 ratios and the upper and lower cut-offs of sCD26, we were able to discriminate patients with and without recurrent disease. We propose that the measurement of serum sCD26 during the follow-up of patients diagnosed of colorectal cancer could be valuable for the early detection of local and distant recurrence. A large, randomized, prospective trial should be performed to confirm our findings.
PMCID: PMC4161426  PMID: 25210927
3.  Evaluation of pleural effusion sCD26 and DPP-IV as diagnostic biomarkers in lung disease 
Scientific Reports  2014;4:3999.
In this study, we measured ADA and DPP-IV enzymatic activity and sCD26 concentration in 150 pleural effusion (PE) samples and tested for correlations between these and other cellular and biochemical measures. We found that DPP-IV in particular might improve the specificity (but not the sensitivity) of the ADA test for diagnosis of pulmonary tuberculosis, since half of the false ADA positive results in non-tuberculous PE were also DPP-IV positive. A percentage of patients with malignant PE were sCD26 or DPP-IV positive; however, some patients with benign PE also tested positive. As a pattern associated with DPP-IV (but not the CD26 protein) was observed in PE, we searched for a finding that might increase the value of these biomarkers for diagnosis of malignancy. The observed pattern was related to the presence of leukocytes, as indicated by correlations with the cell count, and to a band of 180 kDa, detected by immunoblotting.
PMCID: PMC3915277  PMID: 24499783
4.  Serum activity of DPPIV and its expression on lymphocytes in patients with melanoma and in people with vitiligo 
BMC Immunology  2012;13:48.
Dipeptidyl peptidase IV, a multifunctional serine protease, is implicated in regulation of malignant transformation, promotion and further progression of cancer, exerting tumor-suppressing or even completely opposite - tumor-promoting activities.
The aim of present research was to determine the serum DPPIV activity, as well as the percentages of CD26+ lymphocytes, CD26+ overall white blood cells and the mean fluorescence intensity of CD26 expression on lymphocytes in patients with melanoma, people with vitiligo and in healthy controls.
The activity of DPPIV in serum was determined by colorimetric test. Expression of DPPIV (as CD26) on immunocompetent peripheral white blood cells was done using flow cytometry analysis.
Data from our study show for the first time statistically significant decrease: in the serum DPPIV activity, in the percentage of CD26+ overall white blood cells and in the percentage of lymphocytes in patients with melanoma in comparison to healthy control people. In addition, significantly lower serum DPPIV activity was found in the group of patients with melanoma in relation to people with vitiligo too.
This study indicates the need for exploring the cause and the importance of the disturbances in the serum DPPIV activity and in the CD26 expression on immunocompetent cells in complex molecular mechanisms underlying the development and progression of melanoma.
PMCID: PMC3464610  PMID: 22908963
CD26 expression; DPPIV serum activity; Melanoma; Vitiligo
5.  Serum CD26 is related to histopathological polyp traits and behaves as a marker for colorectal cancer and advanced adenomas 
BMC Cancer  2010;10:333.
Serum CD26 (sCD26) levels were previously found diminished in colorectal cancer (CRC) patients compared to healthy donors, suggesting its potential utility for early diagnosis. Therefore we aimed to estimate the utility of the sCD26 as a biomarker for CRC and advanced adenomas in a high-risk group of patients. The relationship of this molecule with polyp characteristics was also addressed.
sCD26 levels were measured by ELISA in 299 symptomatic and asymptomatic patients who had undergone a colonoscopy. Patients were diagnosed as having no colorectal pathology, non-inflammatory or inflammatory bowel disease, polyps (hyperplastic, non-advanced and advanced adenomas) or CRC.
At a 460 ng/mL cut-off, the sCD26 has a sensitivity and specificity of 81.8% (95% CI, 64.5-93.0%) and 72.3% (95% CI, 65.0-77.2%) for CRC regarding no or benign colorectal pathology. Clinicopathological analysis of polyps showed a relationship between the sCD26 and the grade of dysplasia and the presence of advanced adenomas. Hence, a 58.0% (95% CI, 46.5-68.9%) sensitivity detecting CRC and advanced adenomas was obtained, with a specificity of 75.5% (95% CI, 68.5-81.0%).
Our preliminary results show that measurement of the sCD26 is a non-invasive and reasonably sensitive assay, which could be combined with others such as the faecal occult blood test for the early diagnosis and screening of CRC and advanced adenomas. Additional comparative studies in average-risk populations are necessary.
PMCID: PMC2912863  PMID: 20584285
6.  Soluble CD26 Levels and Its Association to Epidemiologic Parameters in a Sample Population 
Disease markers  2010;27(6):311-316.
Introduction: Previous studies have suggested the use of soluble CD26 (sCD26) as a tumour marker for the detection of colorectal cancer (CRC) and advanced adenomas. The aim of this study was to assess the sCD26 concentration in a large cohort to evaluate its association to epidemiologic parameters and CRC-related symptoms/pathologies.
Subjects and methods: Serum samples were collected from 2,754 putatively healthy individuals with ages ranging from 30–65 years, and with personal or familial history of polyps, CRC and/or CR symptoms. sCD26 levels were measured by ELISA.
Results: No association was found between the sCD26 concentration and age (< 50 and ≥ 50), the personal or familial history of polyps or CRC, rectal bleeding, haemorrhoids or diverticula. However, sCD26 was related to non-inflammatory benign pathologies (excluding rectal bleeding, changes in bowel habits, haemorrhoids, diverticula) and to inflammatory benign pathologies.
Discussion: Our results confirm that the sCD26 can be easily offered and evaluated in a large cohort. Additionally, the validation of sCD26 as a tumour marker for screening and case-finding purposes requires a further comparison with an established non-invasive test like the faecal occult blood.
PMCID: PMC3835055  PMID: 20075514
sCD26; serum levels; colorectal cancer; digestive pathologies; marker

Results 1-6 (6)