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

Abstract

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.

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

“…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).…”

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

“…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.…”

“…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.…”

“…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].…”

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

“…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.…”