Abstract
Background
Cancer antigen 19-9 (CA19-9) is widely used as a marker of pancreatic cancer tumor burden and response to therapy. Synthesis of CA19-9 and its circulating levels are determined by variants encoding the fucosyltransferases, FUT2 and FUT3. Individuals can be grouped into one of four functional FUT groups (FUT3-null, FUT-low, FUT-intermediate, FUT-high), each with its own CA19-9 reference range based on its predicted capacity to produce CA19-9. The authors hypothesized that a FUT variant-based CA19-9 tumor marker gene test could improve the prognostic performance of CA19-9.
Methods
Preoperative and pre-treatment CA19-9 levels were measured, and FUT variants were determined in 449 patients who underwent surgery for pancreatic ductal adenocarcinoma (PDAC) at Johns Hopkins Hospital between 2010 and 2020, including 270 patients who underwent neoadjuvant therapy. Factors associated with recurrence-free and overall survival were determined in Cox proportional hazards models.
Results
Higher preoperative CA19-9 levels were associated with recurrence and mortality for patients in the higher-FUT groups (FUT-intermediate, FUT-high for mortality, with adjustment for other prognostic factors; hazard ratio [HR], 1.34 and 1.58, respectively; P < 0.001), but not for those in the lower-FUT groups (FUT3-null, FUT-low). As a tumor marker, CA19-9 levels of 100 U/ml or lower after neoadjuvant therapy and normalization of CA19-9 based on FUT group were more sensitive but less specific predictors of evidence for a major pathologic response to therapy (little/no residual tumor) and of early recurrence (within 6 months).
Conclusion
Among patients undergoing pancreatic cancer resection, a CA19-9 tumor marker gene test modestly improved the prognostic performance of CA19-9.
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Acknowledgments
This work was supported by NIH grants (U01210170, R01CA176828 CA62924), Susan Wojcicki and Dennis Troper, and a Stand Up to Cancer–Lustgarten Foundation Pancreatic Cancer Interception Translational Cancer Research grant (grant no. SU2C-AACR-DT25-17). Stand Up to Cancer is a program of the Entertainment Industry Foundation. SU2C research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. Michael Goggins is the Sol Goldman Professor of Pancreatic Cancer Research. A Fujimoto Medical System scholarship was awarded to Yohei Ando and the International Research Fund for Subsidy of Kyushu University School of Medicine Alumni.
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Ando, Y., Dbouk, M., Blackford, A.L. et al. Using a CA19-9 Tumor Marker Gene Test to Assess Outcome After Pancreatic Cancer Surgery. Ann Surg Oncol 31, 2902–2912 (2024). https://doi.org/10.1245/s10434-024-14942-5
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DOI: https://doi.org/10.1245/s10434-024-14942-5