A New CA19-9 Cutoff Value Identifies Lewis Antigen Status and Refines Prognostic Stratification in PDAC

Area of Science:

• Oncology
• Biochemistry
• Genetics

Background:

• Carbohydrate antigen 19-9 (CA19-9) is a tumor marker for pancreatic ductal adenocarcinoma (PDAC).
• Approximately 10% of PDAC patients are Lewis-negative nonproducers (FUT3-null), limiting CA19-9 utility.
• Identifying prognostic subgroups in PDAC is crucial for effective treatment strategies.

Purpose of the Study:

• To define the prognosis of FUT3-null PDAC.
• To establish a CA19-9 cutoff for identifying FUT3-null PDAC patients in clinical practice.
• To improve risk stratification for PDAC patients using CA19-9 levels.

Main Methods:

• Germline whole-exome sequencing in 615 PDAC patients to determine FUT2/FUT3 genotypes.
• Receiver operating characteristic (ROC) analysis to identify optimal CA19-9 cutoffs.
• Maximally selected rank statistics to stratify overall survival (OS) in training and validation sets.

Main Results:

• FUT3-null patients had significantly lower median baseline CA19-9 levels (2.4 U/mL) compared to FUT3-intact patients (496 U/mL).
• Median OS for FUT3-null patients (13.5 months) was comparable to FUT3-intact patients with CA19-9 >200 U/mL (12.9 months).
• An optimal CA19-9 cutoff of 7 U/mL was identified for FUT3-null status with high accuracy (87.9%).
• A dual-threshold model (≤7 and >200 U/mL) stratified patients into four prognostic groups with distinct median OS.

Conclusions:

• CA19-9 nonproducers (likely FUT3-null) represent a high-risk PDAC subgroup.
• A CA19-9 level ≤7 U/mL serves as a practical surrogate for identifying this subgroup.
• A dual-threshold CA19-9 model improves risk stratification when genotyping is unavailable.