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Landscape of sialylation patterns identify biomarkers for diagnosis and prediction of response to anti-TNF therapy in crohn’s disease

ABSTRACT: Crohn’s disease (CD), a subtype of inflammatory bowel disease (IBD), causes chronic gastrointestinal tract inflammation. Thirty percent of patients do not respond to anti-tumor necrosis factor (TNF) therapy. Sialylation is involved in the pathogenesis of IBD. We aimed to identify potential biomarkers for diagnosing CD and predicting anti-TNF medication outcomes in CD. Three potential biomarkers (SERPINB2, TFPI2, and SLC9B2) were screened using bioinformatics analysis and machine learning based on sialylation-related genes. Moreover, the combined model of SERPINB2, TFPI2, and SLC9B2 showed excellent diagnostic value in both the training and validation cohorts. Importantly, a Sial-score was constructed based on the expression of SERPINB2, TFPI2, and SLC9B2. The Sial-low group showed a lower level of immune infiltration than the Sial-high group. Anti-TNF therapy was effective for 94.4% of patients in the Sial-low group but only 15.8% in the Sial-high group. The Sial-score had an outstanding ability to predict and distinguish between responders and non-responders. Our comprehensive analysis indicates that SERPINB2, TFPI2, and SLC9B2 play essential roles in pathogenesis and anti-TNF therapy resistance in CD. Furthermore, it may provide novel concepts for customizing treatment for individual patients with CD.

SUBMITTER: Ye C

PROVIDER: S-EPMC9702336 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundUstekinumab and vedolizumab are both effective for treating Crohn's disease (CD). However, no head-to-head trials have been conducted thus far. We aimed to compare the effectiveness of ustekinumab and vedolizumab in CD patients either naïve or exposed to tumor necrosis factor-alpha inhibitors (TNFi).MethodsPatients treated with vedolizumab or ustekinumab for luminal CD were included from six centers in China from May 2020 to July 2023. Steroid-free remission, clinical remission, objective response, and remission at Weeks 26 and 52 were evaluated in a retrospective multicenter propensity score-weighted cohort.FindingsA total of 536 patients were included (386 ustekinumab, and 150 vedolizumab). After adjustment, ustekinumab showed higher rates of clinical remission (56.4% vs. 47.8%, P = 0.005), steroid-free remission (55.4% vs. 46.1%, P = 0.003), and objective response (67.8% vs. 42.7%, P < 0.001) than vedolizumab at Week 26. At Week 52, ustekinumab exhibited significantly higher rates of clinical remission (65.8% vs. 37.5%, P < 0.001), steroid-free remission (65.8% vs. 37.5%, P < 0.001), objective response (66.7% vs. 23.8%, P < 0.001), and objective remission (31.4% vs. 12.7%, P < 0.001). Subgroup analyses revealed that ustekinumab had higher rates of clinical remission, steroid-free remission, and objective response at Weeks 26 and 52, and objective remission at Week 52 in TNFi-exposed patients, while ustekinumab showed higher rates of objective response at Weeks 26 and 52 and clinical remission, steroid-free remission and objective remission at Week 52 in TNFi-naïve patients. Adverse event rates were similar between the groups (4.9% ustekinumab vs. 6.7% vedolizumab, P = 0.423).InterpretationUstekinumab showed superior clinical and objective outcomes compared to vedolizumab, with comparable safety outcomes. The therapeutic superiority was observed in both short-term and long-term phases in TNFi-exposed patients, and the long-term phase in TNFi-naïve patients.FundingNational Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Key Research Projects of the Sixth Affiliated Hospital, Sun Yat-sen University, the program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and National Key Clinical Discipline.

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Landscape of sialylation patterns identify biomarkers for diagnosis and prediction of response to anti-TNF therapy in crohn’s disease

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