Dataset Information

Mucins and associated O-glycans based immunoprofile for stratification of colorectal polyps: clinical implication for improved colon surveillance.

ABSTRACT: Sessile serrated adenoma/polyps (SSA/P) are premalignant lesions of colorectal cancer that are difficult to distinguish histologically from hyperplastic polyps (HP) of minimal to no malignant potential. Specific markers for differentiating SSA/P from HP can aid clinicians for optimizing colon surveillance intervals. The present study investigates the potential of mucins and associated O-glycans to distinguish SSA/P from HP. Expression of colonic mucins (MUC1, MUC4, MUC17, MUC2, and MUC5AC) and O-glycans [Sialyl LewisA (CA19-9) and Tn/Sialyl-Tn on MUC1] were analyzed in HP (n=33), SSA/P (n=39), and tubular adenoma (TA) (n=36) samples by immunohistochemistry. A significantly reduced expression of MUC4 (p=0.0066), elevated expression of MUC17 (p=0.0002), and MUC5AC (p<0.0001) was observed in SSA/P cases in comparison to HP cases. Interestingly, significantly higher number of SSA/P cases (p<0.0001) exhibited MUC5AC expression in the goblet cells as well as filled the crypt lumen compared to only goblet cells in majority of the HP cases. Improved diagnostic potential was revealed by multivariate logistic regression analysis where combinatorial panel of MUC5AC/MUC17 discriminated SSA/P from HP (SN/SP=85/82%). Finally, the decision tree model based marker panel (CA19-9/MUC17/MUC5AC) predicted HP, SSA/P and TA with SN/SP of 58%/95%, 79%/90% and 97%/83%, respectively. Overall, the mucin and associated O-glycan based panel defined in the present study could aid in discriminating SSA/P from HP to devise better colon surveillance strategies.

SUBMITTER: Krishn SR

PROVIDER: S-EPMC5351688 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Mucins and associated O-glycans based immunoprofile for stratification of colorectal polyps: clinical implication for improved colon surveillance.

Krishn Shiv Ram SR Kaur Sukhwinder S Sheinin Yuri M YM Smith Lynette M LM Gautam Shailendra K SK Patel Asish A Jain Maneesh M Juvvigunta Vasthala V Pai Priya P Lazenby Audrey J AJ Roy Hemant K HK Batra Surinder K SK

Oncotarget 20170101 4

Sessile serrated adenoma/polyps (SSA/P) are premalignant lesions of colorectal cancer that are difficult to distinguish histologically from hyperplastic polyps (HP) of minimal to no malignant potential. Specific markers for differentiating SSA/P from HP can aid clinicians for optimizing colon surveillance intervals. The present study investigates the potential of mucins and associated O-glycans to distinguish SSA/P from HP. Expression of colonic mucins (MUC1, MUC4, MUC17, MUC2, and MUC5AC) and O ...[more]

PMID: 27705923

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Project description:BackgroundColorectal cancer is a leading cause of mortality and morbidity in Ontario. Most cases of colorectal cancer are preventable through early diagnosis and the removal of precancerous polyps. Colon capsule endoscopy is a non-invasive test for detecting colorectal polyps.ObjectivesThe objectives of this analysis were to evaluate the cost-effectiveness and the impact on the Ontario health budget of implementing colon capsule endoscopy for detecting advanced colorectal polyps among adult patients who have been referred for computed tomographic (CT) colonography.MethodsWe performed an original cost-effectiveness analysis to assess the additional cost of CT colonography and colon capsule endoscopy resulting from misdiagnoses. We generated diagnostic accuracy data from a clinical evidence-based analysis (reported separately), and we developed a deterministic Markov model to estimate the additional long-term costs and life-years lost due to false-negative results. We then also performed a budget impact analysis using data from Ontario administrative sources. One-year costs were estimated for CT colonography and colon capsule endoscopy (replacing all CT colonography procedures, and replacing only those CT colonography procedures in patients with an incomplete colonoscopy within the previous year). We conducted this analysis from the payer perspective.ResultsUsing the point estimates of diagnostic accuracy from the head-to-head study between colon capsule endoscopy and CT colonography, we found the additional cost of false-positive results for colon capsule endoscopy to be $0.41 per patient, while additional false-negatives for the CT colonography arm generated an added cost of $116 per patient, with 0.0096 life-years lost per patient due to cancer. This results in an additional cost of $26,750 per life-year gained for colon capsule endoscopy compared with CT colonography. The total 1-year cost to replace all CT colonography procedures with colon capsule endoscopy in Ontario is about $2.72 million; replacing only those CT colonography procedures in patients with an incomplete colonoscopy in the previous year would cost about $740,600 in the first year.LimitationsThe difference in accuracy between colon capsule endoscopy and CT colonography was not statistically significant for the detection of advanced adenomas (≥ 10 mm in diameter), according to the head-to-head clinical study from which the diagnostic accuracy was taken. This leads to uncertainty in the economic analysis, with results highly sensitive to changes in diagnostic accuracy.ConclusionsThe cost-effectiveness of colon capsule endoscopy for use in patients referred for CT colonography is $26,750 per life-year, assuming an increased sensitivity of colon capsule endoscopy. Replacement of CT colonography with colon capsule endoscopy is associated with moderate costs to the health care system.

Project description:Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. These carbohydrates differ from those of the surrounding non-cancerous tissues and contribute to the malignant phenotype of the cancer cells by promoting proliferation, metastasis, and immunosuppression. However, due to tumor tissue heterogeneity and technological limitations, TACAs are insufficiently explored. Methods: A workflow was established to decode the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts. Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC.

Dataset Information

Mucins and associated O-glycans based immunoprofile for stratification of colorectal polyps: clinical implication for improved colon surveillance.

Publications

Mucins and associated O-glycans based immunoprofile for stratification of colorectal polyps: clinical implication for improved colon surveillance.

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