Abstract
CD26 is an ectoenzyme with dipeptidyl peptidase IV activity expressed on a variety of cell types. Although the function of the high concentration of serum-soluble CD26 (sCD26) is unknown, it may be related to the cleavage of biologically active polypeptides. As CD26 or enzymatic activity levels were previously associated with cancer, we examined the potential diagnostic and prognostic value of preoperative sCD26 measurements by ELISA in colorectal carcinoma patients. We found a highly significant difference between sCD26 levels in healthy donors (mean 559.7 ± 125.5 μg l−1) and cancer patients (mean 261.7 ± 138.1 μg l−1) (P < 0.001). A cut-off at 410 μg l−1 gave 90% sensitivity with 90% specificity which means that the diagnostic efficiency of sCD26 is higher than that shown by other markers, particularly in patients at early stages. Moreover, sCD26 as a variable is not related with Dukes’ stage classification, age, gender, tumour location or degree of differentiation. With a follow-up of 2 years until recurrence, preliminary data show that sCD26 can be managed as a prognostic variable of early carcinoma patients. In addition, the origin of sCD26 is discussed. © 2000 Cancer Research Campaign
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References
American Society of Clinical Oncology (1996) Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. J Clin Oncol 14: 2843–2877
American Society of Clinical Oncology (1998) 1997 update of recommendations for the use of tumor markers in breast and colorectal cancer. J Clin Oncol 16: 793–795
Ansorge S, Schön E and Kunz D (1991) Membrane-bound peptidases of lymphocytes: functional implications. Biomed Biochim Acta 50: 799–807
Ayude D, Rodríguez-Berrocal FJ, Fernándes-Rodrìguez J, Martínez-Zorzano VS, de Carlos A, Gil-Martin E and Páez de la Cadeno M (2000) Value of α-L-Fucosidase activity in the diagnosis of colorectal cancer. Oncology, (in press)
Bauvois B (1988) A collagen-binding glycoprotein on the surface of mouse fibroblasts is identified as dipeptidyl peptidase IV. Biochem J 252: 723–371
Bauvois B, Sancéau J and Wietzerbin J (1992) Human U937 cell surface peptidase activities: characterization and degradative effect on tumour necrosis factor-α. Eur J Immunol 22: 923–930
Beck JR and Shultz EK (1986) The use of relative operating characteristic (ROC) curves in test performance evaluation. Arch Pathol Lab Med 110: 13–20
Cintin C, Johansen JS, Christensen IJ, Price PA, Sorensen S and Nielsen HJ (1999) Serum YKL-40 and colorectal cancer. Br J Cancer 79: 1494–1499
Cohn SL, Lincoln ST and Rosen ST (1986) Present status of serum tumour markers in diagnosis, prognosis and evaluation of therapy. Cancer Invest 4: 305–327
Cordero OJ, Salgado FJ, Vinuela JE and Nogueira M (1997) Interleukin-12 enhances CD26 expression and dipeptidyl peptidase IV function on human activated lymphocytes. Immunobiology 197: 522–533
Dang NH, Torimoto Y, Schlossman SF and Morimoto C (1990) Human VCD4 helper T cell activation: functional involvement of two distinct collagen receptors, 1F7 and VLA integrin family. J Exp Med 172: 649–652
De Meester I, Korom S, Van Damme J and Scharpé S (1999) CD26, let it cut or cut it down. Immunol Today 20: 367–375
De Meester I, Vanham G, Kestens L, Vanhoof G, Bosmans E, Gigase P and Scharpé S (1994) Binding of the adenosine deaminase to the lymphocyte surface via CD26. Eur J Immunol 24: 566–570
Devesa JM, Morales V, Enriquez JM, Nuno J, Camunas J, Hernandez MJ and Avila C (1988) Colorectal cancer: the bases for a comprehensive follow-up. Dis Colon Rectum 31: 636–652
Drucker DJ, Shi Q, Crivici A, Sumner-Smith M, Tavares W, Hill M, DeForest L, Cooper S and Brubaker PL (1997) Regulation of the biological activity of glucagon-like peptide 2 by dipeptidyl peptidase IV. Nat Biotechnol 15: 673–677
Duke-Cohan JS, Morimoto C, Rocker JA and Schlossman SF (1996) Serum high molecular weight dipeptidyl peptidase IV (CD26) is similar to a novel antigen DPPT-L released from activated T cells. J Immunol 156: 1714–1721
Dukes CE (1932) The classification of cancer of the rectum. J Pathol Bacteriol 35: 323–332
Fernández-Rodríguez J, Ayude D, Páez de la Cadena M, Martínez-Zorzano VS, de Carlos A, Caride-Castro A, de Castro G and Rodríguez-Berrocal FJ (2000) α-L-Fucosidase enzyme in the prediction of colorectal cancer patients at high risk of tumor recurrence. Cancer Detect 24: 143–149
Fleischer B (1994) CD26: a surface protease involved in T-cell activation. Immunol Today 15: 180–184
Fujita K, Hirano M, Tokunaga K, Nagatsu I, Nagatsu T and Sakakibara S (1977) Serum glycylproline p-nitroanilidase activity in blood cancers. Clin Chim Acta 81: 215–217
Gotoh H, Hagihara M, Nagatsu T, Iwata H and Miura T (1988) Activity of dipeptidyl peptidase IV and post-proline cleaving enzyme in sera from osteoporotic patients. Clin Chem 34: 2499–2501
Gruss HJ, Pinto A, Duyster J, Poppema S and Herrmann F (1997) Hodgkin’s disease: a tumour with disturbed immunological pathways. Immunol Today 18: 156–163
Hakomori S (1989) Aberrant glycosylation in tumours and tumour-associated carbohydrate antigens. Adv Cancer Res 52: 257–331
Hino M, Nagatsu T, Kakumu S, Okuyama S, Yoshii Y and Nagatsu I (1975) Glycylprolyl beta-naphthylamidase activity in human serum. Clin Chim Acta 62: 5–11
Holten-Andersen MN, Murphy G, Nielsen HJ, Pedersen AN, Christensen IJ, Hoyer-Hansen G, Brunner N and Stephens RW (1999) Quantitation of TIMP-1 in plasma of healthy blood donors and patients with advanced cancer. Br J Cancer 80: 495–503
Iwaki-Egawa S, Watanabe Y, Kikuya Y and Fujimoto Y (1998) Dipeptidyl peptidase IV from human serum: purification, characterization, and N-terminal amino acid sequence. J Biochem (Tokyo) 124: 428–433
Iwata S and Morimoto C (1999) CD26/dipeptidyl peptidase IV in context. The different roles of a multifunctional ectoenzyme in malignant transformation. J Exp Med 190: 301–306
Kameoka J, Tanaka T, Nojima Y, Schlossman SF and Morimoto C (1993) Direct association of adenosine deaminase with a T cell activation antigen CD26. Science 261: 466–469
Kaplan EL and Meier P (1958) Nonparametric estimation from incomplete observations. Am Stat Assoc 53: 457–481
Kojima K, Mihara R, Sakai T, Togari A, Matsui T, Shinpo K, Fujita K, Fukasawa K, Harada M and Nagatsu T (1987) Serum activities of dipeptidyl-aminopeptidase II and dipeptidyl-aminopeptidase IV in tumour-bearing animals and in cancer patients. Biochem Med Metab Biol 37: 35–41
Lakatos PL, Firneisz G, Rakoczy G, Selmeci L and Szalay F (1999) Elevated serum dipeptidyl peptidase IV (CD26, EC 3.4.14.5) activity in patients with primary biliary cirrhosis. J Hepatol 30: 740
Maes M, Lin A, Bonaccorso S, Vandoolaeghe E, Song C, Goossens F, De Meester I, Degroote J, Neels H, Scharpe S and Janca A (1999) Lower activity of serum peptidases in abstinent alcohol-dependent patients. Alcohol 17: 1–6
Maes M, De Meester I, Verkerk R, De Medts P, Wauters A, Vanhoof G, Vandoolaeghe E, Neels H and Scharpe S (1997) Lower serum dipeptidyl peptidase IV activity in treatment resistant major depression: relationships with immune-inflammatory markers. Psychoneuroendocrinology 22: 65–78
Medeiros MS and Turner AJ (1994) Post-secretory processing of regulatory peptides: the pancreatic polypeptide family as a model example. Biochimie 76: 283–287
Michelassi F, Vannucci L, Ayala JJ, Chappel R, Goldberg R and Block GE (1990) Local recurrence after curative resection of colorectal adenocarcinoma. Surgery 108: 787–792
Mogi M, Harada M, Hiraoka BY, Fukasawa K, Komatsu M and Nagatsu T (1986) Sandwich enzyme-immunoassay for dipeptidyl aminopeptidase IV in the serum of people with oral cancer. Arch Oral Biol 31: 505–507
Morrison ME, Vijayasaradhi S, Engelstein D, Albino AP and Houghton AN (1993) A marker for neoplastic progression of human melanocytes is a cell surface ectopeptidase. J Exp Med 177: 1135–1143
Nano R, Capelli E, Civallero M, Lorusso L, Argentina F, Bonizzoni E and Ceroni M (1997) Activated lymphoid cells in human gliomas: morphofunctional and cytochemical evidence. Anticancer Res 17: 107–111
Obrand DI and Gordon PH (1997) Incidence and patterns of recurrence following curative resection for colorectal carcinoma. Dis Colon Rectum 40: 15–24
O'Hara RJ, Greenman J, Drew PJ, McDonald AW, Duthie GS, Lee PW and Monson JR (1998) Impaired interleukin-12 production is associated with a defective anti-tumour response in colorectal cancer. Dis Colon Rectum 41: 460–463
Oravecz T, Pall M, Roderiquez G, Gorrell MD, Ditto M, Nguyen NY, Boykins R, Unsworth E and Norcross MA (1997) Regulation of the receptor specificity and function of the chemokine RANTES (regulated on activation, normal T cell expressed and secreted) by dipeptidyl peptidase IV (CD26)-mediated cleavage. J Exp Med 186: 1865–1872
Pangalos MN, Neefs JM, Somers M, Verhasselt P, Bekkers M, van der Helm L, Fraiponts E, Ashton D and Gordon RD (1999) Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity. J Biol Chem 274: 8470–8483
Perner F, Gyuris T, Rakoczy G, Sarvary E, Gorog D, Szalay F, Kunos I, Szonyi L, Peterfy M and Takacs L (1999) Dipeptidyl peptidase activity of CD26 in serum and urine as a marker of cholestasis: experimental and clinical evidence. J Lab Clin Med 134: 56–67
Proost P, De Meester Y, Schols D, Struyf S, Lambeir A-M, Wuyts A, Opdenakker G, De Clercq E, Scharpé S and Van Damme J (1998) Amino-terminal truncation of chemokines by CD26/Dipeptidyl peptidase IV. Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection. J Biol Chem 273: 7222–7227
Schmitz T, Underwood R, Khiroya R, Bachovchin WW and Huber BT (1996) Potentiation of the immune response in HIV-1+ individuals. J Clin Invest 97: 1545–1549
Sharpé S, De Meester Y, Vanhoof G, Hendriks D, Van Sand M, Van Camp K and Yaron A (1988) Assay of Dipeptidyl peptidase IV in serum by fluorimetry of 4-methoxy-2-naphthylamine. Clin Chem 34: 2299–2305
Shibuya-Saruta H, Kasahara Y and Hashimoto Y (1996) Human serum dipeptidyl peptidase IV (DPPIV) and its unique properties. J Clin Lab Anal 10: 435–440
Sliutz G, Tempfer C, Winkler S, Kohlberger P, Reinthaller A and Kainz C (1995) Immunohistochemical and serological evaluation of CD44 splice variants in human ovarian cancer. Br J Cancer 72: 1494–1497
Stipa S, Nicolanti V, Botti C, Cosimelli M, Mannella E, Stipa F, Giannarelli D, Bangrazi C and Cavaliere R (1991) Local recurrence after curative resection for colorectal cancer: frequency, risk factors and treatment. J Surg Oncol, 155–160
Ten Kate J, Wijnen JT, Boldewijn J, Khan PM and Bosman FT (1985) Immunohistochemical localization of adenosine deaminase complexing protein in intestinal mucosa and in colorectal adenocarcinoma as a marker for tumour cell heterogeneity. Histochem J 17: 23–31
Ten Kate J, Dinjens WN, Meera Khan P and Bosman FT (1986a) Adenosine deaminase complexing protein in cancer studies. Anticancer Res 6: 983–988
Ten Kate J, van den Ingh HF, Khan PM and Bosman FT (1986b) Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma. Int J Cancer 37: 479–485
Uematsu T, Urade M, Yamaoka M and Yoshioka W (1996) Reduced expression of dipeptidyl peptidase (DPP) IV in peripheral blood T lymphocytes of oral cancer patients. J Oral Pathol Med 25: 507–512
Uematsu T, Urade M and Yamaoka M (1998) Decreased expression and release of dipeptidyl peptidase IV (CD26) in cultured peripheral blood T lymphocytes of oral cancer patients. J Oral Pathol Med 27: 106–110
Underwood R, Chiravuri M, Lee H, Schmitz T, Kabcenell AK, Yardley K and Huber BT (1999) Sequence, purification, and cloning of an intracellular serine protease, quiescent cell proline dipeptidase. J Biol Chem 274: 34053–34058
Van Der Velden VH, Naber BA, Van Hal PT, Overbeek SE, Hoogsteden HC and Versnel MA (1999) Peptidase activities in serum and bronchoalveolar lavage fluid from allergic asthmatics – comparison with healthy non-smokers and smokers and effects of inhaled glucocorticoids. Clin Exp Allergy 29: 813–823
Wesley UV, Albino AP, Tiwari S and Houghton AN (1999) A role for dipeptidyl peptidase IV in suppressing the malignant phenotype of melanocytic cells. J Exp Med 190: 311–322
Werb Z (1997) ECM and cell surface proteolysis: regulating cellular ecology. Cell 91: 439–442
Yamane N, Tsujitani S, Makino M, Maeta M and Kaibara N (1999) Soluble CD44 variant 6 as a prognostic indicator in patients with colorectal cancer. Oncology 56: 232–238
Zweig MH and Campbell G (1993) Receiver-operating characteristic (ROC) plots: A fundamental evaluation tool in clinical medicine. Clin Chem 39: 561–577
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Cordero, O., Ayude, D., Nogueira, M. et al. Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer. Br J Cancer 83, 1139–1146 (2000). https://doi.org/10.1054/bjoc.2000.1410
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DOI: https://doi.org/10.1054/bjoc.2000.1410
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