CGH: Serum carboxypeptidase activity and genotype-stratified CA19-9 levels can detect the development of early pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States, with a 5-year survival rate of just 9%.

However, survival rates are much higher for patients with early-stage disease, especially those with stage I disease, with a 5-year survival rate of 80%
after surgical resection.
Pancreatic surveillance increases the proportion of
patients diagnosed with stage I disease.
But current pancreatic surveillance protocols rely on pancreatic imaging
.
During pancreatic surveillance, circulating biomarkers are needed to improve early cancer detection, especially for stage I pancreatic cancer
.
One biomarker that may serve as an early PDAC marker is serum carboxypeptidase a (CPA).

CPA activity is elevated in some patients with pancreatic cancer, but not in
patients with pancreatic atrophy.
The levels of several common tumor markers are affected by the gene
variants they express or secrete.
For example, variants that affect the function of genes responsible for CA19-9 synthesis and secretion affect CA19-9 levels
.
By understanding which variants affect normal levels of CA19-9 and other tumor markers, variant-specific tumor marker reference ranges can be developed to improve their diagnostic accuracy
.
Therefore, this study aims to use serum CPA assessed with CA19-9 as a marker for early pancreatic cancer
.

The researchers first measured serum CPA activity levels in a control group of 345 people who underwent pancreatic monitoring, and all patients were divided into 2 groups, with group 1 used to establish a reference range
.
Look for variants within the CPA1 locus to determine their correlation with pancreatic CPA1 expression to determine if these variants correlate
with serum CPA levels.
The remaining patients were validated
as a second group.
A total of 190 patients with resectable PDAC were evaluated
in this trial.

The results of the study showed that the secondary alleles rs6955723 or rs2284682 with 1 or more CPA1 variants had significantly higher serum CPA levels in the control group than those without CPA variants (P = .
001).

None of the PDAC cases with pancreatic atrophy had elevated
CPA.
In 122 cases of PDAC without atrophy, the cut-off value for the diagnosis of serum CPA was defined by the participant's CPA1 variant, resulting in a diagnostic sensitivity of 18% at 99% specificity (95% confidence interval [CI], 11.
7-26); Combining CPA with variation-stratified CA19-9 yielded a sensitivity of 68.
0% (95% CI, 59.
0–76.
2), compared with 63.
1% (95% CI, 53.
9–71.
7) for CA19-9 alone; In cases of stage I PDAC, the diagnostic sensitivity was 51.
9% (95% CI, 31.
9–71.
3), compared with 37.
0% (95% CI, 19.
4–57.
6)
with CA19-9 alone.

Therefore, this study demonstrates in population studies that serum CPA activity is diagnostic prior to the onset of pancreatic atrophy and can be used as a marker for
local PDACs, including stage I disease.

Original source:

Haruyoshi Tanaka.
et al.
Serum Carboxypeptidase Activity and Genotype-Stratified CA19-9 to Detect Early-Stage Pancreatic Cancer.
Clinical Gastroenterology and Hepatology.
2022.