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Br J Cancer. 2000 Nov; 83(9): 1139–1146.
PMCID: PMC2363587

Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer


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

Keywords: colorectal cancer, serum CD26, CD26/DPP-IV, diagnosis, tumour recurrence

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  • Ansorge S, Schön E, Kunz D. Membrane-bound peptidases of lymphocytes: functional implications. Biomed Biochim Acta. 1991;50(4-6):799–807. [PubMed]
  • Bauvois B, Sancéau J, Wietzerbin J. Human U937 cell surface peptidase activities: characterization and degradative effect on tumor necrosis factor-alpha. Eur J Immunol. 1992 Apr;22(4):923–930. [PubMed]
  • Beck JR, Shultz EK. The use of relative operating characteristic (ROC) curves in test performance evaluation. Arch Pathol Lab Med. 1986 Jan;110(1):13–20. [PubMed]
  • Cintin C, Johansen JS, Christensen IJ, Price PA, Sørensen S, Nielsen HJ. Serum YKL-40 and colorectal cancer. Br J Cancer. 1999 Mar;79(9-10):1494–1499. [PMC free article] [PubMed]
  • Cohn SL, Lincoln ST, Rosen ST. Present status of serum tumor markers in diagnosis, prognosis, and evaluation of therapy. Cancer Invest. 1986;4(4):305–327. [PubMed]
  • Cordero OJ, Salgado FJ, Viñuela JE, Nogueira M. Interleukin-12 enhances CD26 expression and dipeptidyl peptidase IV function on human activated lymphocytes. Immunobiology. 1997 Nov;197(5):522–533. [PubMed]
  • Dang NH, Torimoto Y, Schlossman SF, Morimoto C. Human CD4 helper T cell activation: functional involvement of two distinct collagen receptors, 1F7 and VLA integrin family. J Exp Med. 1990 Aug 1;172(2):649–652. [PMC free article] [PubMed]
  • De Meester I, Korom S, Van Damme J, Scharpé S. CD26, let it cut or cut it down. Immunol Today. 1999 Aug;20(8):367–375. [PubMed]
  • De Meester I, Vanham G, Kestens L, Vanhoof G, Bosmans E, Gigase P, Scharpé S. Binding of adenosine deaminase to the lymphocyte surface via CD26. Eur J Immunol. 1994 Mar;24(3):566–570. [PubMed]
  • Devesa JM, Morales V, Enriquez JM, Nuño J, Camuñas J, Hernandez MJ, Avila C. Colorectal cancer. The bases for a comprehensive follow-up. Dis Colon Rectum. 1988 Aug;31(8):636–652. [PubMed]
  • Drucker DJ, Shi Q, Crivici A, Sumner-Smith M, Tavares W, Hill M, DeForest L, Cooper S, Brubaker PL. Regulation of the biological activity of glucagon-like peptide 2 in vivo by dipeptidyl peptidase IV. Nat Biotechnol. 1997 Jul;15(7):673–677. [PubMed]
  • Duke-Cohan JS, Morimoto C, Rocker JA, Schlossman SF. Serum high molecular weight dipeptidyl peptidase IV (CD26) is similar to a novel antigen DPPT-L released from activated T cells. J Immunol. 1996 Mar 1;156(5):1714–1721. [PubMed]
  • Fernández-Rodríguez J, Ayude D, de la Cadena MP, Martínez-Zorzano VS, de Carlos A, Caride-Castro A, de Castro G, Rodríguez-Berrocal FJ. Alpha-L-fucosidase enzyme in the prediction of colorectal cancer patients at high risk of tumor recurrence. Cancer Detect Prev. 2000;24(2):143–149. [PubMed]
  • Fleischer B. CD26: a surface protease involved in T-cell activation. Immunol Today. 1994 Apr;15(4):180–184. [PubMed]
  • Fujita K, Hirano M, Tokunaga K, Nagatsu I, Nagatsu T, Sakakibara S. Serum glycylproline p-nitroanilidase activity in blood cancers. Clin Chim Acta. 1977 Dec 1;81(2):215–217. [PubMed]
  • Gotoh H, Hagihara M, Nagatsu T, Iwata H, Miura T. Activity of dipeptidyl peptidase IV and post-proline cleaving enzyme in sera from osteoporotic patients. Clin Chem. 1988 Dec;34(12):2499–2501. [PubMed]
  • Gruss HJ, Pinto A, Duyster J, Poppema S, Herrmann F. Hodgkin's disease: a tumor with disturbed immunological pathways. Immunol Today. 1997 Apr;18(4):156–163. [PubMed]
  • Hakomori S. Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens. Adv Cancer Res. 1989;52:257–331. [PubMed]
  • Hino M, Nagatsu T, Kakumu S, Okuyama S, Yoshii Y, Nagatsu I. Glycylprolyl beta-naphthylamidase activity in human serum. Clin Chim Acta. 1975 Jul 9;62(1):5–11. [PubMed]
  • Holten-Andersen MN, Murphy G, Nielsen HJ, Pedersen AN, Christensen IJ, Høyer-Hansen G, Brünner N, Stephens RW. Quantitation of TIMP-1 in plasma of healthy blood donors and patients with advanced cancer. Br J Cancer. 1999 May;80(3-4):495–503. [PMC free article] [PubMed]
  • Iwaki-Egawa S, Watanabe Y, Kikuya Y, Fujimoto Y. Dipeptidyl peptidase IV from human serum: purification, characterization, and N-terminal amino acid sequence. J Biochem. 1998 Aug;124(2):428–433. [PubMed]
  • Iwata S, Morimoto C. CD26/dipeptidyl peptidase IV in context. The different roles of a multifunctional ectoenzyme in malignant transformation. J Exp Med. 1999 Aug 2;190(3):301–306. [PMC free article] [PubMed]
  • Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C. Direct association of adenosine deaminase with a T cell activation antigen, CD26. Science. 1993 Jul 23;261(5120):466–469. [PubMed]
  • Kojima K, Mihara R, Sakai T, Togari A, Matsui T, Shinpo K, Fujita K, Fukasawa K, Harada M, Nagatsu T. Serum activities of dipeptidyl-aminopeptidase II and dipeptidyl-aminopeptidase IV in tumor-bearing animals and in cancer patients. Biochem Med Metab Biol. 1987 Feb;37(1):35–41. [PubMed]
  • Lakatos PL, Firneisz G, Rákóczy G, Selmeci L, Szalay F. Elevated serum dipeptidyl peptidase IV (CD26, EC activity in patients with primary biliary cirrhosis. J Hepatol. 1999 Apr;30(4):740–740. [PubMed]
  • Maes M, Lin A, Bonaccorso S, Vandoolaeghe E, Song C, Goossens F, De Meester I, Degroote J, Neels H, Scharpé S, et al. Lower activity of serum peptidases in abstinent alcohol-dependent patients. Alcohol. 1999 Jan;17(1):1–6. [PubMed]
  • Maes M, De Meester I, Verkerk R, De Medts P, Wauters A, Vanhoof G, Vandoolaeghe E, Neels H, Scharpé S. Lower serum dipeptidyl peptidase IV activity in treatment resistant major depression: relationships with immune-inflammatory markers. Psychoneuroendocrinology. 1997 Feb;22(2):65–78. [PubMed]
  • Medeiros MS, Turner AJ. Post-secretory processing of regulatory peptides: the pancreatic polypeptide family as a model example. Biochimie. 1994;76(3-4):283–287. [PubMed]
  • Michelassi F, Vannucci L, Ayala JJ, Chappel R, Goldberg R, Block GE. Local recurrence after curative resection of colorectal adenocarcinoma. Surgery. 1990 Oct;108(4):787–793. [PubMed]
  • Mogi M, Harada M, Hiraoka BY, Fukasawa K, Komatsu M, Nagatsu T. Sandwich enzyme-immunoassay for dipeptidyl aminopeptidase IV in the serum of people with oral cancer. Arch Oral Biol. 1986;31(7):505–507. [PubMed]
  • Morrison ME, Vijayasaradhi S, Engelstein D, Albino AP, Houghton AN. A marker for neoplastic progression of human melanocytes is a cell surface ectopeptidase. J Exp Med. 1993 Apr 1;177(4):1135–1143. [PMC free article] [PubMed]
  • Nano R, Capelli E, Civallero M, Lorusso L, Argentina F, Bonizzoni E, Ceroni M. Activated lymphoid cells in human gliomas: morphofunctional and cytochemical evidence. Anticancer Res. 1997 Jan-Feb;17(1A):107–111. [PubMed]
  • Obrand DI, Gordon PH. Incidence and patterns of recurrence following curative resection for colorectal carcinoma. Dis Colon Rectum. 1997 Jan;40(1):15–24. [PubMed]
  • O'Hara RJ, Greenman J, Drew PJ, McDonald AW, Duthie GS, Lee PW, Monson JR. Impaired interleukin-12 production is associated with a defective anti-tumor response in colorectal cancer. Dis Colon Rectum. 1998 Apr;41(4):460–463. [PubMed]
  • Oravecz T, Pall M, Roderiquez G, Gorrell MD, Ditto M, Nguyen NY, Boykins R, Unsworth E, Norcross MA. 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. 1997 Dec 1;186(11):1865–1872. [PMC free article] [PubMed]
  • Pangalos MN, Neefs JM, Somers M, Verhasselt P, Bekkers M, van der Helm L, Fraiponts E, Ashton D, Gordon RD. Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity. J Biol Chem. 1999 Mar 26;274(13):8470–8483. [PubMed]
  • Perner F, Gyuris T, Rákóczy G, Sárváry E, Görög D, Szalay F, Kunos I, Szönyi L, Péterfy M, Takács L. Dipeptidyl peptidase activity of CD26 in serum and urine as a marker of cholestasis: experimental and clinical evidence. J Lab Clin Med. 1999 Jul;134(1):56–67. [PubMed]
  • Proost P, De Meester I, Schols D, Struyf S, Lambeir AM, Wuyts A, Opdenakker G, De Clercq E, Scharpé S, Van Damme J. 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. 1998 Mar 27;273(13):7222–7227. [PubMed]
  • Schmitz T, Underwood R, Khiroya R, Bachovchin WW, Huber BT. Potentiation of the immune response in HIV-1+ individuals. J Clin Invest. 1996 Mar 15;97(6):1545–1549. [PMC free article] [PubMed]
  • Scharpé S, De Meester I, Vanhoof G, Hendriks D, van Sande M, Van Camp K, Yaron A. Assay of dipeptidyl peptidase IV in serum by fluorometry of 4-methoxy-2-naphthylamine. Clin Chem. 1988 Nov;34(11):2299–2301. [PubMed]
  • Shibuya-Saruta H, Kasahara Y, Hashimoto Y. Human serum dipeptidyl peptidase IV (DPPIV) and its unique properties. J Clin Lab Anal. 1996;10(6):435–440. [PubMed]
  • Sliutz G, Tempfer C, Winkler S, Kohlberger P, Reinthaller A, Kainz C. Immunohistochemical and serological evaluation of CD44 splice variants in human ovarian cancer. Br J Cancer. 1995 Dec;72(6):1494–1497. [PMC free article] [PubMed]
  • Stipa S, Nicolanti V, Botti C, Cosimelli M, Mannella E, Stipa F, Giannarelli D, Bangrazi C, Cavaliere R. Local recurrence after curative resection for colorectal cancer: frequency, risk factors and treatment. J Surg Oncol Suppl. 1991;2:155–160. [PubMed]
  • Ten Kate J, Wijnen JT, Boldewijn J, Khan PM, Bosman FT. Immunohistochemical localization of adenosine deaminase complexing protein in intestinal mucosa and in colorectal adenocarcinoma as a marker for tumour cell heterogeneity. Histochem J. 1985 Jan;17(1):23–31. [PubMed]
  • Ten Kate J, Dinjens WN, Meera Khan P, Bosman FT. Adenosine deaminase complexing protein in cancer studies. Anticancer Res. 1986 Sep-Oct;6(5):983–988. [PubMed]
  • ten Kate J, van den Ingh HF, Khan PM, Bosman FT. Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma. Int J Cancer. 1986 Apr 15;37(4):479–485. [PubMed]
  • Uematsu T, Urade M, Yamaoka M, Yoshioka W. Reduced expression of dipeptidyl peptidase (DPP) IV in peripheral blood T lymphocytes of oral cancer patients. J Oral Pathol Med. 1996 Oct;25(9):507–512. [PubMed]
  • Uematsu T, Urade M, Yamaoka M. Decreased expression and release of dipeptidyl peptidase IV (CD26) in cultured peripheral blood T lymphocytes of oral cancer patients. J Oral Pathol Med. 1998 Mar;27(3):106–110. [PubMed]
  • Underwood R, Chiravuri M, Lee H, Schmitz T, Kabcenell AK, Yardley K, Huber BT. Sequence, purification, and cloning of an intracellular serine protease, quiescent cell proline dipeptidase. J Biol Chem. 1999 Nov 26;274(48):34053–34058. [PubMed]
  • Van Der Velden VH, Naber BA, Van Hal PT, Overbeek SE, Hoogsteden HC, Versnel MA. 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. 1999 Jun;29(6):813–823. [PubMed]
  • Wesley UV, Albino AP, Tiwari S, Houghton AN. A role for dipeptidyl peptidase IV in suppressing the malignant phenotype of melanocytic cells. J Exp Med. 1999 Aug 2;190(3):311–322. [PMC free article] [PubMed]
  • Werb Z. ECM and cell surface proteolysis: regulating cellular ecology. Cell. 1997 Nov 14;91(4):439–442. [PubMed]
  • Yamane N, Tsujitani S, Makino M, Maeta M, Kaibara N. Soluble CD44 variant 6 as a prognostic indicator in patients with colorectal cancer. Oncology. 1999 Apr;56(3):232–238. [PubMed]
  • Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 1993 Apr;39(4):561–577. [PubMed]

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