IPAH disease worsening linked to 2 tumor biomarkers: Study

Higher AFP and CA125 biomarker levels also tied to poorer prognosis

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Elevated levels of two tumor biomarkers, AFP and CA125, were found to predict disease worsening in people with idiopathic pulmonary arterial hypertension (IPAH) in a new study from China.

“Changes in AFP over time serve as an indicator of disease alteration, enabling detection of disease progression or treatment response,” the researchers wrote.

CA125, meanwhile, “had prognostic value in low-risk patients, allowing for more accurate risk stratification and prediction of disease outcomes,” according to the team.

Their study, “Tumor biomarkers in evaluating the severity and prognosis of idiopathic pulmonary arterial hypertension: A comprehensive analysis,” was published in the journal Clinical and Translational Science.

PAH is marked by high blood pressure in the pulmonary arteries, the blood vessels that supply the lungs. Inflammation is a known contributor to disease progression, but current assessments of disease severity do not reflect a patient’s inflammatory status. IPAH is the term for pulmonary arterial hypertension from an unknown cause.

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Seeking a link to immune response

Research has shown that tumor biomarkers are elevated in patients with heart disorders. However, whether they could serve as biomarkers of heightened immune responses in PAH has not been determined.

To learn more, scientists at Peking Union Medical College, in Beijing, analyzed clinical data from 315 IPAH patients followed at their center from January 2014 to February 2021. Women accounted for 78% of the group, and the average age was 39.5.

The team assessed the blood levels of five tumor biomarkers: alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA153, and CA199.

Within a median of 718 days, or almost two years, 124 patients (39.4%) saw their symptoms worsen. Fifteen patients died, and 109 had to be re-hospitalized due to right heart failure, disease progression, or the need to escalate their medication.

The patients whose symptoms worsened had more advanced PH at the start of the study, as shown by lower exercise tolerance, poorer blood flow, higher levels of heart-failure biomarker NT-proBNP, and poorer World Health Organization functional classification (WHO FC) ratings than those without clinical worsening.

The results showed they also had significantly higher levels of AFP — a mean of 4.17 ng/mL, compared with 3.24 ng/mL for those whose symptoms didn’t worsen — and CA125, with a mean of 20.32 U/ml, compared with 17.1 U/mL.

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Biomarker levels point to worsening PAH

Additional lab work showed higher levels of alanine aminotransaminase and total bilirubin — markers of liver damage — and of the inflammation markers C-reactive protein and erythrocyte sedimentation rate.

Higher levels of tumor biomarkers, except CA153, generally correlated with higher C-reactive protein, NT-proBNP, WHO FC rating, and pulmonary vascular resistance, a measure of the resistance of blood vessels to blood flow.

Statistical analysis showed that AFP and CA125 were two independent predictors of clinical worsening.

Patients with CA125 below 36.48 U/mL had a significantly better prognosis than those with higher levels. A similar finding was seen for an AFP cut-off value of 3.45 ng/mL. For AFP, each increase of 1 ng/mL was associated with a 5.4% higher risk of disease worsening.

As the risk increased, so did tumor biomarker levels, researchers found when stratifying patients according to 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) PH guidelines. The predictive value of CA125 was maintained in the low-risk patients.

The findings suggest that “AFP and CA125 can independently predict long-term outcome of patients with IPAH,” according to the researchers.

“Changes of AFP over time were associated with clinical worsening,” the team wrote. Further, they added that “CA125 had prognostic value in low-risk patients according to guideline recommended risk stratification.”

One limitation, the researchers noted, is that the study only looked at patients with IPAH.

“Our results should be interpreted with caution when dealing with other forms of PH,” the team wrote.

A Conversation With Rare Disease Advocates