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Introduction

Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC-UC) is considered a unique inflammatory bowel disease (IBD) entity. PSC diagnosis in an IBD individual entails a significantly higher risk of gastrointestinal cancer; however, biomarkers for identifying patients with UC at risk for PSC are lacking. We, therefore, performed a thorough PSC-UC biomarker study, starting from archived colonic tissue.

Methods

Proteins were extracted out of formalin-fixed paraffin-embedded proximal colon samples from PSC-UC (n = 9), UC (n = 7), and healthy controls (n = 7). Patients with IBD were in clinical and histological remission, and all patients with UC had a history of pancolitis. Samples were processed by the multienzyme digestion FASP and subsequently analyzed by liquid chromatography-tandem mass spectrometry. Candidate proteins were replicated in an independent cohort (n: PSC-UC = 16 and UC = 21) and further validated by immunohistochemistry.

Results

In the discovery step, 7,279 unique proteins were detected. The top 5 most differentiating proteins (PSC-UC vs UC) based on linear regression analysis were selected for replication. Of these, 1-acetylglycerol-3-phosphate O-acyltransferase 1 (AGPAT1) was verified as higher in PSC-UC than UC (P = 0.009) in the replication cohort. A difference on the group level was also confirmed by immunohistochemistry, showing more intense AGPAT1 staining in patients with PSC-UC compared with UC.

Discussion

We present AGPAT1 as a potential colonic biomarker for differentiating PSC-UC from UC. Our findings have possible implication for future PSC-IBD diagnostics and surveillance."xsd:string
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http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/author"Wisniewski J.R."xsd:string
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/author"Carlson M."xsd:string
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/author"Lindskog C."xsd:string
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/author"Rorsman F."xsd:string
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/author"Eriksson N."xsd:string
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/author"Aberg M."xsd:string
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/author"Wanders A."xsd:string
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/author"Vessby J."xsd:string
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/author"Gabrysch K."xsd:string
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/author"Zettl K."xsd:string
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/name"Clin Transl Gastroenterol"xsd:string
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http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/title"AGPAT1 as a Novel Colonic Biomarker for Discriminating Between Ulcerative Colitis With and Without Primary Sclerosing Cholangitis."xsd:string
http://purl.uniprot.org/citations/35363634http://purl.uniprot.org/core/volume"13"xsd:string
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