Sialyl-Tn antigen as a marker of colon cancer risk in ulcerative colitis: Relation to dysplasia and DNA aneuploidy

Karlén, Per; Young, Elaine; Broström, Olle; Löfberg, Robert; Tribukait, Bernhard; Öst, Åke; Bodian, Carol; Itzkowitz, Steven H.

doi:10.1016/s0016-5085(98)70018-6

Cited by 65 publications

(25 citation statements)

References 21 publications

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“…The expression of STn is an early event in the molecular pathogenesis of both sporadic-and colitis-induced colon cancer, 46 which correlates with tumor progression and poor prognosis 36 and identifies patients at risk for development of colonic neoplasia. 47 Similar to STn, the expression of MUC1 is also increased in adenomas with high malignant potential. 48 Autoantibodies to various underglycosylated forms of MUC1 and possibly MUC4 are therefore expected in patients with colorectal adenomas with high malignant potential, and future studies will examine the potential correlation between existence of glycopeptide autoantibodies and malignant potential in patients with adenomas.…”

Section: Discussionmentioning

confidence: 93%

Seromic profiling of colorectal cancer patients with novel glycopeptide microarray

Pedersen

Blixt

Bennett

et al. 2011

Intl Journal of Cancer

127

101

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Cancer-associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant posttranslational variants of proteins are likely to induce autoantibodies, and changes in O-linked glycosylation represent one of the most important cancer-associated post-translational modifications (PTMs). Short aberrant O-glycans on proteins may introduce novel glycopeptide epitopes that can elicit autoantibodies because of lack of tolerance. Technical barriers, however, have hampered detection of such glycopeptide-specific autoantibodies. Here, we have constructed an expanded glycopeptide array displaying a comprehensive library of glycopeptides and glycoproteins derived from a panel of human mucins (MUC1, MUC2, MUC4, MUC5AC, MUC6 and MUC7) known to have altered glycosylation and expression in cancer. Seromic profiling of patients with colorectal cancer identified cancer-associated autoantibodies to a set of aberrant glycopeptides derived from MUC1 and MUC4. The cumulative sensitivity of the array analysis was 79% with a specificity of 92%. The most prevalent of the identified autoantibody targets were validated as authentic cancer immunogens by showing expression of the epitopes in cancer using novel monoclonal antibodies. Our study provides evidence for the value of glycopeptides and other PTM-peptide arrays in diagnostic measures.Colorectal cancer develops in a multistep process that arises from genetic or epigenetic alterations.1 Most colorectal cancers can be treated by removal of early malignant lesions, 2,3 but despite this colorectal cancer remains the second most common cause of cancer-related death in the western world. 4 Current screening techniques, which include fecal occult blood, sigmoid and colonoscopy and computed tomographic colonography, are complicated with low compliance and high cost.5 Therefore, there is a need for biomarkers, which can identify colorectal cancer at early stages and aid in the surveillance and identification of high-risk populations.Broad genomic and proteomic approaches for identification of biomarkers have so far failed to develop simple, reliable and noninvasive screening test for early detection of colorectal cancer.6 Current serum assays detecting cancer glycoproteins such as CEA and CA-19-9 have limited use for early stages with low specificity and sensitivity. 7,8 As an alternative, circulating autoantibodies elicited by exposure to aberrant cancer proteins lacking immunological tolerance are emerging as promising biomarkers for the early detection of cancer.9-13 However, relatively few autoantibody epitopes have been identified and characterized to date.14 In a small study, we recently demonstrated the existence of such cancerassociated autoantibodies to the aberrantly O-glycosylated MUC1 mucin in patients with breast, ovarian and prostate cancer at time of diagnosis.15 These results provide basis for further discovery of autoantibody targets with the aim to increase sensitivity and organ specificity of biomarker assays through signatures of autoantibo...

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Section: Discussionmentioning

confidence: 93%

Seromic profiling of colorectal cancer patients with novel glycopeptide microarray

Pedersen

Blixt

Bennett

et al. 2011

Intl Journal of Cancer

127

101

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“…STn was expressed in most aneuploid areas but was also found in diploid, non-dysplastic mucosa. Karlen et al 67 found that STn expression and DNA aneuploidy were independent markers of neoplastic transformation and concluded that STn expression might complement dysplasia and aneuploidy for identification of risk for colonic neoplasia in ulcerative colitis. Four of five patients in their study with aneuploidy but without dysplasia expressed STn earlier than aneuploidy.…”

Section: Molecular Improvementsmentioning

confidence: 99%

Cancer surveillance in ulcerative colitis

Chambers

Warren

Jewell

et al. 2005

British Journal of Surgery

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“…Although both sporadic colorectal cancer and colitic cancer arise from dysplastic precursor lesions and share some molecular alterations, the nature of the dysplasia and the frequency and timing of several of the key molecular changes differ enough to support our hypothesis that in contrast to sporadic colorectal cancer, colitic cancer could be prevented with either the early intervention of effective anti-inflammatory strategies or through cancer surveillance using biomarkers (5,6). With regard to biomarkers for colitic cancer risk, aneuploidy, p53, mucin-associated sialyl-Tn antigen expression, and loss of transgelin hold promise (7)(8)(9); however, they are not yet practical for clinical use because a panel of genes or proteins engaged in colitic cancer needs further validation. Therefore, as a potential biomarker for tumor surveillance, it is important to investigate whether a potent anti-inflammatory drug or strategy could be applied for the prevention of colitic cancer through either the abolishment or the delay of carcinogenic processes initiated or promoted by sustaining inflammation.…”

Section: Introductionmentioning

confidence: 99%

Novel Application of Proton Pump Inhibitor for the Prevention of Colitis-Induced Colorectal Carcinogenesis beyond Acid Suppression

Kim

Lee

Hong

et al. 2010

Cancer Prevention Research

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Colitis-associated cancers arise in the setting of chronic inflammation wherein an "inflammationdysplasia-carcinoma" sequence prevails. Based on our previous findings in which the proton pump inhibitor could impose significant levels of anti-inflammatory, antiangiogenic, and selective apoptosis induction beyond gastric acid suppression, we investigated whether omeprazole could prevent the development of colitis-associated cancer in a mouse model induced by repeated bouts of colitis. Omeprazole, 10 mg/kg, was given i.p. all through the experimental periods for colitis-associated carcinogenesis. Molecular changes regarding inflammation and carcinogenesis were compared between control groups and colitis-associated cancer groups treated with omeprazole in addition to chemopreventive outcome. Nine of 12 (75.0%) mice in the control group developed multiple colorectal tumors, whereas tumors were noted in only 3 of 12 (25.0%) mice treated with daily injections of omeprazole. The cancer-preventive results of omeprazole treatment was based on significant decreases in the levels of nitric oxide, thiobarbituric acid-reactive substance, and interleukin-6 accompanied with attenuated expressions of tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2. The expressions of matrix metalloproteinase (MMP)-9, MMP-11, and MT1-MMMP were significantly decreased in mice treated with omeprazole in accordance with significant decreases in the number of β-catenin-accumulated crypts. A significant induction of apoptosis was observed in tumor tissue treated with omeprazole. Omeprazole could block the trophic effect of gastrin in colon epithelial cells. The significant anti-inflammatory, antioxidative, and antimutagenic activities of omeprazole played a cancer-preventive role against colitisinduced carcinogenesis, and our novel in vivo evidence is suggestive of chemopreventive action independent of gastric acid suppression. Cancer Prev Res; 3(8); 963-74. ©2010 AACR.

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Sialyl-Tn antigen as a marker of colon cancer risk in ulcerative colitis: Relation to dysplasia and DNA aneuploidy

Cited by 65 publications

References 21 publications

Seromic profiling of colorectal cancer patients with novel glycopeptide microarray

Seromic profiling of colorectal cancer patients with novel glycopeptide microarray

Cancer surveillance in ulcerative colitis

Novel Application of Proton Pump Inhibitor for the Prevention of Colitis-Induced Colorectal Carcinogenesis beyond Acid Suppression

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