Dataset Information

Agrin in the Muscularis Mucosa Serves as a Biomarker Distinguishing Hyperplastic Polyps from Sessile Serrated Lesions.

ABSTRACT: PURPOSE:Sessile serrated lesions (SSL) are precursors to colon carcinoma, and their distinction from other polyps, in particular hyperplastic polyps (HP), presents significant diagnostic challenges. We evaluated expression patterns in colonic polyps of previously identified colon carcinoma-associated extracellular matrix (ECM) proteins to identify markers distinguishing SSLs from other polyps. EXPERIMENTAL DESIGN:Gene-expression analyses of ECM proteins were performed using publicly available data on preneoplastic colonic polyps. In parallel, we evaluated by IHC the expression of agrin (AGRN) in over 400 colonic polyps, including HP, SSL with and without dysplasia, traditional serrated adenomas (TSA), and tubular adenomas (TA), and compared the consistency of standard histologic diagnosis of SSLs by experienced gastrointestinal pathologists with that of AGRN IHC. RESULTS:Differential gene expression analysis and IHC identified AGRN, serine peptidase inhibitor (SERPINE2), and TIMP metallopeptidase inhibitor 1 (TIMP1) elevated in SSLs and HPs but decreased in TAs and absent in normal colon. AGRN-positive basal laminae were noted in all TA, TSA, HP, and SSL in distinguishable patterns, whereas other polyps and normal mucosa were negative. SSL with or without dysplasia consistently showed IHC staining for AGRN in the muscularis mucosae, which was absent in HP, TSA, TA, and other polyps. In contrast, histologic evaluation showed only weak interobserver agreement (kappa value = 0.493) in distinguishing SSLs. CONCLUSIONS:Muscularis mucosae-based AGRN immunostaining is a novel biomarker to distinguish SSL from HP, TSA, and TA, with a specificity of 97.1% and sensitivity of 98.9% and can assist in diagnosis of morphologically challenging colonic polyps.

SUBMITTER: Rickelt S

PROVIDER: S-EPMC7073301 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Agrin in the Muscularis Mucosa Serves as a Biomarker Distinguishing Hyperplastic Polyps from Sessile Serrated Lesions.

Rickelt Steffen S Condon Charlene C Mana Miyeko M Whittaker Charlie C Pfirschke Christina C Roper Jatin J Patil Deepa T DT Brown Ian I Mattia Anthony R AR Zukerberg Lawrence L Zhao Qing Q Chetty Runjan R Lauwers Gregory Y GY Neyaz Azfar A Leijssen Lieve G J LGJ Boylan Katherine K Yilmaz Omer H OH Deshpande Vikram V Hynes Richard O RO

Clinical cancer research : an official journal of the American Association for Cancer Research 20191218 6

<h4>Purpose</h4>Sessile serrated lesions (SSL) are precursors to colon carcinoma, and their distinction from other polyps, in particular hyperplastic polyps (HP), presents significant diagnostic challenges. We evaluated expression patterns in colonic polyps of previously identified colon carcinoma-associated extracellular matrix (ECM) proteins to identify markers distinguishing SSLs from other polyps.<h4>Experimental design</h4>Gene-expression analyses of ECM proteins were performed using public ...[more]

PMID: 31852835

Similar Datasets

Project description:BackgroundSessile serrated adenomas/polyps are distinguished from hyperplastic colonic polyps subjectively by their endoscopic appearance and histological morphology. However, hyperplastic and sessile serrated polyps can have overlapping morphological features resulting in sessile serrated polyps diagnosed as hyperplastic. While sessile serrated polyps can progress into colon cancer, hyperplastic polyps have virtually no risk for colon cancer. Objective measures, differentiating these types of polyps would improve cancer prevention and treatment outcome.MethodsRNA-seq training data set and Affimetrix, Illumina testing data sets were obtained from Gene Expression Omnibus (GEO). RNA-seq single-end reads were filtered with FastX toolkit. Read mapping to the human genome, gene abundance estimation, and differential expression analysis were performed with Tophat-Cufflinks pipeline. Background correction, normalization, and probe summarization steps for Affimetrix arrays were performed using the robust multi-array method (RMA). For Illumina arrays, log2-scale expression data was obtained from GEO. Pathway analysis was implemented using Bioconductor package GSAR. To build a platform-independent molecular classifier that accurately differentiates sessile serrated and hyperplastic polyps we developed a new feature selection step. We also developed a simple procedure to classify new samples as either sessile serrated or hyperplastic with a class probability assigned to the decision, estimated using Cantelli's inequality.ResultsThe classifier trained on RNA-seq data and tested on two independent microarray data sets resulted in zero and three errors. The classifier was further tested using quantitative real-time PCR expression levels of 45 blinded independent formalin-fixed paraffin-embedded specimens and was highly accurate. Pathway analyses have shown that sessile serrated polyps are distinguished from hyperplastic polyps and normal controls by: up-regulation of pathways implicated in proliferation, inflammation, cell-cell adhesion and down-regulation of serine threonine kinase signaling pathway; differential co-expression of pathways regulating cell division, protein trafficking and kinase activities.ConclusionsMost of the differentially expressed pathways are known as hallmarks of cancer and likely to explain why sessile serrated polyps are more prone to neoplastic transformation than hyperplastic. The new molecular classifier includes 13 genes and may facilitate objective differentiation between two polyps.

Dataset Information

Agrin in the Muscularis Mucosa Serves as a Biomarker Distinguishing Hyperplastic Polyps from Sessile Serrated Lesions.

Publications

Agrin in the Muscularis Mucosa Serves as a Biomarker Distinguishing Hyperplastic Polyps from Sessile Serrated Lesions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets