Small RNA sequencing of sessile serrated polyps identifies microRNA profile associated with colon cancer.

Sessile serrated adenoma/polyps (SSA/Ps) of the colon account for 20-30% of all colon cancers. Small non-coding RNAs, including microRNAs (miRNAs), may function as oncogenes or tumor suppressor genes involved in cancer development. Small RNA sequencing (RNA-seq) was used to characterize miRNA profiles in SSA/Ps, hyperplastic polyps (HPs), adenomatous polyps and paired uninvolved colon. Our 108 small RNA-seq samples' results were compared to small RNA-seq data from 212 colon cancers from the Cancer Genome Atlas. Twenty-three and six miRNAs were differentially expressed in SSA/Ps compared to paired uninvolved colon and HPs, respectively. Differential expression of MIR31-5p, MIR135B-5p and MIR378A-5p was confirmed by RT-qPCR. SSA/P-specific miRNAs are similarly expressed in colon cancers containing genomic aberrations described in serrated cancers. Correlation of miRNA expression with consensus molecular subtypes suggests more than one subtype is associated with the serrated neoplasia pathway. Canonical pathway analysis suggests many of these miRNAs target growth factor signaling pathways.

Endocuff assisted colonoscopy significantly increases sessile serrated adenoma detection in veterans.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer related deaths in the United States. Colonoscopy is the gold standard for the detection of CRC. There are many colonoscopy quality measures and among these the adenoma detection rate (ADR) has demonstrated a significant impact in reducing mortality from CRC. The primary aim of our study was to compare ADR and distribution of polyp type in patients undergoing Endocuff-assisted colonoscopy (EAC) versus standard colonoscopy (SC) in a VA system. METHODS: Retrospective data was collected from 496 patients who underwent routine screening, surveillance and diagnostic colonoscopies either via SC from January 6, 2014 through March 12, 2014 or EAC from September 24, 2014 through February 19, 2015. A total of 54 patients were excluded based on a personal history of CRC and prior resection, incomplete colonoscopy due to poor bowel preparation, and removal or loss of Endocuff (EC). Primary outcomes measured and compared were ADR and types of polyps found. RESULTS: The overall ADR in the EAC group was higher at 59.91% versus 50.66% for SC, accounting for a 9% increase (P=0.0508). EAC was able to detect a total of 59 sessile serrated adenoma/polyps (SSA/Ps) compared to SC only detecting 8 (P≤0.0001). There was a significant increase in the SSA/P detection rate with EAC at 15% versus 3% in the SC group (P≤0.0001). CONCLUSIONS: EAC significantly increases the detection of SSA/P and has shown a trend in improving ADR in our veteran population.

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

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.

Human intestinal spirochetosis is significantly associated with sessile serrated adenomas/polyps.

It remains unclear whether or not human intestinal spirochetosis (HIS) has any associated symptoms or lesions. In this study, we assessed the prevalence of HIS in sessile serrated adenomas/polyps (SSA/Ps) and their possible association. Following identification of early cecal cancer with SSA/P accompanied by a colonization of HIS, we went on to conduct a retrospective case-control study using endoscopically resected SSA/P specimens to examine the frequency of HIS infection in SSA/Ps. Nineteen SSA/P cases and 172 controls were obtained. The rate of HIS infection was significantly higher at 52.6% (10/19) in the SSA/P cases compared to the controls at 8.1% (14/172). Our SSA/P series were associated with a remarkably higher rate of HIS than controls or than previously reported. This is the first report to provide evidence for potential association between HIS and SSA/Ps.