AGPAT1 as a Novel Colonic Biomarker for Discriminating Between Ulcerative Colitis With and Without Primary Sclerosing Cholangitis

• Published in: Clinical and translational gastroenterology 2022-05, Vol.13 (5), p.e00486-e00486
• Main Authors: Vessby, Johan, Wisniewski, Jacek R., Lindskog, Cecilia, Eriksson, Niclas, Gabrysch, Katja, Zettl, Katharina, Wanders, Alkwin, Carlson, Marie, Rorsman, Fredrik, Åberg, Mikael
• Format: Article
• Language: English
• Subjects: Antibodies; Biomarkers; Biomarkers - metabolism; Cholangitis; Cholangitis, Sclerosing - complications; Cholangitis, Sclerosing - diagnosis; Cholangitis, Sclerosing - pathology; Colitis, Ulcerative - complications; Colitis, Ulcerative - diagnosis; Colitis, Ulcerative - pathology; Colonoscopy; Humans; Inflammatory Bowel Disease; Inflammatory Bowel Diseases; Proteins
• ISSN: 2155-384X; 2155-384X
• DOI: 10.14309/ctg.0000000000000486

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. 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. 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. 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.