Serum levels of cancer antigen (CA) 72-4 are specifically elevated in gout and are a predictor of future flare risk in patients with gouty arthritis, according to study results published in Rheumatology.1
Prediction of gout flares in patients with inflammatory arthritis is difficult because of the lack of known biomarkers. Aberrantly elevated levels of CA72-4, a known tumor marker, have previously been measured in the serum of patients with gout flares.2
Using data from patients treated at the Gout Clinic at the Affiliated Hospital of Qingdao University, China, researchers aimed to identify the link between elevated serum CA72-4 levels and gouty arthritis and evaluate the potential role of CA72-4 as a predictor of gout flares.
Baseline CA72-4 serum levels were measured in patients with gout (n=833; 90.04% men), hyperuricemia (n=120; 96.67% men), septic arthritis (n=43; 51.16% men), rheumatoid arthritis (n=532; 26.32% men), spondyloarthritis (n=243; 70.78% men), osteoarthritis (n=474; 42.98% men), and healthy control participants (n=541; 88.54% men). The median CA72-4 serum level in patients with gouty arthritis was 4.55 U/mL. Patients with hyperuricemia and all types of non-gouty arthritis had serum CA72-4 levels comparable with CA72-4 levels in healthy participants and significantly lower than serum CA72-4 levels in patients with gouty arthritis (P <.001).
The CA72-4 level in patients with gout was significantly higher than the levels in healthy participants and patients with hyperuricemia (P <.001); 42.7% of patients with gouty arthritis had CA72-4 levels above the upper limit of the normal reference range (0-6.9 U/mL). Compared with normal levels, high serum CA72-4 (>6.9 U/mL) was associated with an increase in the percentage of people who experienced gout flares (60.81% vs 70.91%; P =.002), history of type 2 diabetes (4.66% vs 16.34%; P <.001), and fasting glucose levels (950.4±14.6 mg/dL vs 107.3±26.3 mg/dL; P <.001), and a decrease in glucocorticoid use (14.83% vs 8.03%; P =.001).
After multiple linear regression analysis, only flare frequency (effect size [β], 28.676; 95% CI, 14.982-42.371; P <.001) and glucose levels (β, 15.878; 95% CI, 8.688-23.089; P <.001) were independently associated with serum CA72-4 levels.
Serum levels of other tumor markers, including carcinoembryonic antigen (median, 2.04 ng/mL), CA19-9 (median, 8.81 U/mL), and CA125 (median, 10.67 U/mL) were within their respective normal reference ranges for patients with gout, suggesting a specific association with CA72-4 and gout flares.
To determine whether CA72-4 levels could be used as a predictor of flare frequency, patients with gouty arthritis were assessed for flare occurrence at 1, 3, and 6 months. Of the 833 patients with gout, 722 completed 6 months of follow-up. Multiple linear regression analysis indicated that baseline CA72-4 (β, 0.005 U/mL; 95% CI, 0.004-0.006; P <.001), levels of serum uric acid (sUA; β, 0.109 mg/dL; 95% CI, 0.068-0.150; P <.001), glucocorticoid (β, -0.411; 95% CI, -0.687 to -0.136; P =.004) and colchicine use (β, -0.321; 95% CI, -0.503 to -0.139; P =.001) were independently associated with flare occurrence.
Logistic regression identified baseline CA72-4 levels per 50 U/mL (odds ratio [OR], 2.81; 95% CI, 2.10-3.76; P <.001), sUA levels (OR, 1.12; 95% CI, 1.04-1.21; P =.003), and colchicine use (OR, 0.59; 95% CI, 0.42-0.82; P =.002) as independent predictors for risk for future gout flares. High serum CA72-4 levels were the strongest predictor of future flares (hazard ratio [HR], 3.89; 95% CI, 3.10-4.87; P <.001) as identified by multivariable analysis. Serum uric acid (HR, 1.37; 95% CI, 1.12-1.68; P =.002) and colchicine use (HR, 0.76; 95% CI, 0.62-0.93; P =.007) were weakly associated with flare risk.
Compared with patients with normal sUA levels, probability of flares in patients with high CA72-4 was higher in patients with high sUA levels (≥7560 mg/dL; P <.001, although flare frequency was unaffected by sUA status when baseline CA72-4 levels were normal. Colchicine use reduced flare frequency in patients with high CA72-4 (P =.014) but did not alter the probability of flares in individuals with normal CA72-4 levels.
Limitations included the observational nature of the study and the fact that all patients in the study sample were of Chinese ethnicity, which may limit the generalizability of results to other populations.
“In the current study, we observed the unexpected and specifically high expression of CA72-4 in patients [with] gout with active status for flares,” the study investigators concluded. “CA72-4 might be a useful routine test for gout management given its potential use as a marker reflecting gout stability, and thus indicating the chance of future flares.”
1. Bai X, Sun M, He Y, et al. Serum CA72-4 is specifically elevated in gout patients and predicts flares [published online February 22, 2020]. Rheumatology (Oxford). doi:10.1093/rheumatology/keaa046
2. Zhao B, Zhang MM, Xie J et al. An abnormal elevation of serum CA72-4 due to taking colchicine. Clin Chem Lab Med. 2017;56:13-15.