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Published on: April 17, 2026
CT-Derived Radiomic Signature of MUC6 Expression Improves Guideline-Based Risk Stratification in Intraductal
Evan W Davis1,2, Margaret A Park2,3, Toni L Basinski2
1Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Cancers
|July 28, 2026
Summary
Loss of MUC6 expression in intraductal papillary mucinous neoplasms (IPMNs) indicates high-risk pathology. CT-derived radiomics can non-invasively predict MUC6 levels, improving IPMN risk assessment when combined with existing guidelines.
Area of Science:
- Gastroenterology and Hepatology
- Oncology
- Radiology and Imaging
Background:
- Accurate pre-operative identification of high-risk intraductal papillary mucinous neoplasms (IPMNs) is challenging, especially for branch-duct (BD) IPMNs.
- Current guideline-based criteria often fail to fully capture the biologic aggressiveness of these lesions.
Purpose of the Study:
- To investigate if tumoral mucin expression, specifically MUC6, can identify high-risk IPMN pathology (high-grade dysplasia or invasive carcinoma).
- To determine if computed tomography (CT)-derived radiomic features can serve as non-invasive biomarkers to enhance pre-operative risk assessment for IPMNs beyond international consensus guidelines (ICG) criteria.
Main Methods:
- Multiplex immunofluorescence quantified MUC1, MUC2, MUC5AC, and MUC6 expression in 101 surgically resected IPMNs.
- Associations between mucin expression and high-risk pathology were evaluated using statistical tests and receiver operating characteristic (ROC) curves.
- A CT-based radiomic signature was developed to predict low MUC6 expression, and its incremental value beyond ICG high-risk stigmata (HRS) was assessed.
Main Results:
- Reduced MUC6 expression was significantly associated with high-risk IPMN pathology (p = 0.001) with high discriminatory performance (AUC = 0.72).
- A CT-derived radiomic signature predicting low MUC6 expression achieved an AUC of 0.75.
- Integrating the radiomic signature with ICG HRS improved discrimination and decision-curve characteristics compared to HRS alone, particularly for BD-IPMNs.
Conclusions:
- Loss of tumoral MUC6 expression is linked to high-risk IPMN pathology and can be approximated by CT-derived radiomic features, enabling non-invasive molecular phenotyping.
- Combining molecular (MUC6) and imaging (radiomics) biomarkers with guideline-based criteria may enhance pre-operative IPMN risk stratification.
- Prospective external validation is necessary before clinical implementation.