Uncovering novel therapeutic clues for hypercoagulable active ulcerative colitis: novel findings from old data

Zhexuan Yu; Danya Zhao; Yusen Zhang; Kezhan Shen; Shisi Shao; Xiaobo Chen; Jianlong Shu; Guanhua Li

doi:10.1093/gastro/goae105

Uncovering novel therapeutic clues for hypercoagulable active ulcerative colitis: novel findings from old data

Gastroenterol Rep (Oxf). 2024 Dec 28:12:goae105. doi: 10.1093/gastro/goae105. eCollection 2024.

Authors

Zhexuan Yu¹, Danya Zhao², Yusen Zhang¹, Kezhan Shen³, Shisi Shao¹, Xiaobo Chen^{4

5}, Jianlong Shu¹, Guanhua Li^{6

7}

Affiliations

¹ The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P. R. China.
² Department of Gastroenterology, Hangzhou Red Cross Hospital/Hospital of Integrated Chinese and Western Medicine Hospital of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P. R. China.
³ Department of Oncology, Hangzhou Traditional Chinese Medicine Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P. R. China.
⁴ Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, P. R. China.
⁵ Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, Guangdong, P. R. China.
⁶ Department of Cardiovascular Surgery, Shenshan Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Shanwei, Guangdong, P. R. China.
⁷ Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.

Abstract

Background: Hypercoagulability has been shown to act as an important component of ulcerative colitis (UC) pathogenesis and disease activity, and is strongly correlated with the occurrence of venous thromboembolism (VTE). This study aimed at providing novel therapeutic clues for hypercoagulable active UC.

Methods: The coagulation score model was developed using VTE cohorts, and the predictive performance of this model was evaluated by coagulation subtypes of UC patients, which were clustered by the unsupervised method. Subsequently, the response of UC of distinct coagulation types, as identified by the coagulation scoring model, to different biological agents was evaluated. Immunoinflammatory cells and molecules that were associated with hypercoagulable active UC were explored by employing gene set variation analysis, single-sample gene set enrichment analysis, univariate logistic regression analysis, and immunohistochemistry.

Results: A coagulation scoring model was established, which includes five key coagulation factors (ARHGAP35, CD46, BTK, C1QB, and F2R), and accurately distinguished the coagulation subtypes of UC. When comparing anti-TNF-α agents with other biological agents after determining the model, especially golimumab, it showed more effective treatment for hypercoagulable active UC. CXCL8 has been identified as playing an important role in the tightly interconnected network between the immune-inflammatory system and coagulation system in UC. Immunohistochemical analysis showed that the expression of CXCL8, BTK, C1QB, and F2R was upregulated in active UC.

Conclusions: Anti-TNF-α agents have significant therapeutic effects on hypercoagulable active UC, and the strong association between CXCL8, hypercoagulation, and disease activity provides a novel therapeutic insight into hypercoagulable active UC.

Keywords: CXCL8; agents; anti-TNF-α; coagulation score model; hypercoagulable state; ulcerative colitis.