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.

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway

“…The judgment criteria for protein expression were as follows: if the percentage of the stained cells out of the total number of counted cells was < 5%, the score was 0; if the percentage was 5% ~ 25%, the score was 1 point; if the percentage was 26% ~ 50%, the score was 2 points; and if the percentage was more than 50%, the score was 3 points. The final score was the product of the above two scores: 6 points was the maximum value, less than 2 points indicated negative expression, and more than 2 points indicated positive expression [24].…”

MUC1, MUC2, MUC4, MUC5AC, Cdx2: immunohistochemical characteristics in polyps and adenocarcinoma of distal colon

“…Авто-ры предложили использовать данный маркер для дифференциальной диагностики этих полипов [5]. В дальнейшей работе S. R. Krishn et al (2017) предложили использовать MUC4 в комплексе с другими маркерами: снижение экспрессии MUC4, ассоциированное с увеличением экспрессии MUC5АС и MUC17, позволяет выделить полипы с повышенным риском малигнизации [11]. Согласно полученным данным, экспрессия MUC4 в гиперпластических полипах достоверно больше таковой в неизмененной слизистой, а в зубчатых аденомах и аденоматозных полипахзначимо меньше таковой в неизмененной слизистой.…”

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions

“…Aberrant changes in the expression, localization, and glycosylation of colonic mucin have been observed in very early stages of colon cancer. SSA/Ps exhibit an elevated expression of transmembrane mucin MUC17 and secreted mucin MUC5AC in comparison to HP [ 49 ]. Notably, in conjunction with these expressional changes, distinct differences were also observed among the studied polyp groups in MUC5AC and MUC4 localization.…”

“…This signifies the ability of these markers to discriminate benign HP from SSA/P polyp subtypes. In multivariate regression models in conjunction with ROC curve analyses, the combination of MUC17/MUC5AC effectively discriminated SSA/Ps from HP [ 49 ]. The trio (CA 19-9, MUC17, and MUC5AC) emerged as a combined panel for discriminating polyp subtypes and thus accurately classifying colorectal polyps.…”